Propionate attenuates atherosclerosis by immune-dependent regulation of intestinal cholesterol metabolism.

AIMS: Atherosclerotic cardiovascular disease (ACVD) is a major cause of mortality and morbidity worldwide, and increased low-density lipoproteins (LDLs) play a critical role in development and progression of atherosclerosis. Here, we examined for the first time gut immunomodulatory effects of the microbiota-derived metabolite propionic acid (PA) on intestinal cholesterol metabolism. METHODS AND RESULTS: Using both human and animal model studies, we demonstrate that treatment with PA reduces blood total and LDL cholesterol levels. In apolipoprotein E-/- (Apoe-/-) mice fed a high-fat diet (HFD), PA reduced intestinal cholesterol absorption and aortic atherosclerotic lesion area. Further, PA increased regulatory T-cell numbers and interleukin (IL)-10 levels in the intestinal microenvironment, which in turn suppressed the expression of Niemann-Pick C1-like 1 (Npc1l1), a major intestinal cholesterol transporter. Blockade of IL-10 receptor signalling attenuated the PA-related reduction in total and LDL cholesterol and augmented atherosclerotic lesion severity in the HFD-fed Apoe-/- mice. To translate these preclinical findings to humans, we conducted a randomized, double-blinded, placebo-controlled human study (clinical trial no. NCT03590496). Oral supplementation with 500 mg of PA twice daily over the course of 8 weeks significantly reduced LDL [-15.9 mg/dL (-8.1%) vs. -1.6 mg/dL (-0.5%), P = 0.016], total [-19.6 mg/dL (-7.3%) vs. -5.3 mg/dL (-1.7%), P = 0.014] and non-high-density lipoprotein cholesterol levels [PA vs. placebo: -18.9 mg/dL (-9.1%) vs. -0.6 mg/dL (-0.5%), P = 0.002] in subjects with elevated baseline LDL cholesterol levels. CONCLUSION: Our findings reveal a novel immune-mediated pathway linking the gut microbiota-derived metabolite PA with intestinal Npc1l1 expression and cholesterol homeostasis. The results highlight the gut immune system as a potential therapeutic target to control dyslipidaemia that may introduce a new avenue for prevention of ACVDs.

[Left atrial appendage closure for stroke prevention in atrial fibrillation : An update]. / Vorhofohrverschluss zur Schlaganfallprävention bei Vorhofflimmern : Ein Update.

Atrial fibrillation (AF) is one of the most frequent causes of ischemic stroke. Without treatment the annual risk of ischemic stroke is on average approximately 5-6%/year in patients with atrial fibrillation, depending on the overall cardiovascular risk profile. Oral anticoagulation with new oral anticoagulants (NOAC) or vitamin K antagonists (VKA) is recommended for patients with AF and an elevated risk for stroke (CHA2DS2-VASc score ≥1); however, severe bleeding complications are potential reasons for discontinuation of this treatment. Overall, up to 30 % of the patients with AF remain without effective thromboembolism prophylaxis. Left atrial appendage (LAA) closure represents an alternative to pharmaceutical stroke prevention. Catheter-based and surgical LAA closure techniques are available. For catheter-based procedures with closure systems, high implantation success rates and relatively low periprocedural complication rates have been observed in recent registry studies. The reason for the restrained recommendation in the European guidelines is the as yet limited experience from large randomized studies.

Gut Microbiota-Dependent Trimethylamine N-Oxide Predicts Risk of Cardiovascular Events in Patients With Stroke and Is Related to Proinflammatory Monocytes.

Objective- Gut microbiota-dependent metabolites, in particular trimethylamine N-oxide (TMAO), have recently been reported to promote atherosclerosis and thrombosis. Here, we examined for the first time the relation of TMAO and the risk of incident cardiovascular events in patients with recent first-ever ischemic stroke in 2 independent prospective cohorts. Moreover, the link between TMAO and proinflammatory monocytes as a potential contributing factor for cardiovascular risk in stroke patients was studied. Approach and Results- In a first study (n=78), higher TMAO plasma levels were linked with an increased risk of incident cardiovascular events including myocardial infarction, recurrent stroke, and cardiovascular death (fourth quartile versus first quartile; hazard ratio, 2.31; 95% CI, 1.25-4.23; P<0.01). In the second independent validation cohort (n=593), high TMAO levels again heralded marked increased risk of adverse cardiovascular events (fourth quartile versus first quartile; hazard ratio, 5.0; 95% CI, 1.7-14.8; P<0.01), and also after adjustments for cardiovascular risk factors including hypertension, diabetes mellitus, LDL (low-density lipoprotein) cholesterol, and estimated glomerular filtration rate (hazard ratio, 3.3; 95% CI, 1.2-10.9; P=0.04). A significant correlation was also found between TMAO levels and percentage of proinflammatory intermediate CD14++CD16+ monocytes ( r=0.70; P<0.01). Moreover, in mice fed a diet enriched with choline to increase TMAO synthesis, levels of proinflammatory murine Ly6Chigh monocytes were higher than in the chow-fed control group (choline: 9.2±0.5×103 per mL versus control: 6.5±0.5×103 per mL; P<0.01). This increase was abolished in mice with depleted gut microbiota (choline+antibiotics: 5.4±0.7×103 per mL; P<0.001 versus choline). Conclusions- The present study demonstrates for the first time a graded relation between TMAO levels and the risk of subsequent cardiovascular events in patients with recent prior ischemic stroke. Our data support the notion that TMAO-related increase of proinflammatory monocytes may add to elevated cardiovascular risk of patients with increased TMAO levels.

Does Extensive Training at Individuating Novel Objects in Adulthood Lead to Visual Expertise? The Role of Facelikeness.

Human adults have a rich visual experience thanks to seeing human faces since birth, which may contribute to the acquisition of perceptual processes that rapidly and automatically individuate faces. According to a generic visual expertise hypothesis, extensive experience with nonface objects may similarly lead to efficient processing of objects at the individual level. However, whether extensive training in adulthood leads to visual expertise remains debated. One key issue is the extent to which the acquisition of visual expertise depends on the resemblance of objects to faces in terms of the spatial configuration of parts. We therefore trained naive human adults to individuate a large set of novel parametric multipart objects. Critically, one group of participants trained with the objects in a "facelike" stimulus orientation, whereas a second group trained with the same objects but with the objects rotated 180° in the picture plane into a "nonfacelike" orientation. We used a fast periodic visual stimulation EEG protocol to objectively quantify participants' ability to discriminate untrained exemplars before and after training. EEG responses associated with the frequency of identity change in a fast stimulation sequence, which reflects rapid and automatic perceptual processes, were observed over lateral occipital sites for both groups before training. There was a significant, albeit small, increase in these responses after training but only for the facelike group and only to facelike stimuli. Our findings indicate that perceived facelikeness plays a role in visual expertise and highlight how the adult perceptual system exploits familiar spatial configurations when learning new object categories.

The social image of drinking - mass media campaigns may inadvertently increase binge drinking.

Mass media campaigns that promote responsible drinking are rarely tested for their usefulness in reducing heavy alcohol consumption. Existing campaigns that appeal to responsible drinking while simultaneously displaying young people in social drinking situations may even have paradoxical effects. To examine such possible effects, we drew on a real-world media campaign, which we systematically modified on the basis of recent prototype research. We pilot tested questionnaires (using n = 41 participants), developed two different sets of posters in the style of an existing campaign (n = 39) and investigated their effectiveness (n = 102). In the main study, young men were randomly assigned to one of three conditions: sociable or unsociable binge drinker prototype condition or a control group. Outcome variables were intention, behavioural willingness, attitude, subjective norm, self-efficacy, prototype evaluation and prototype similarity with respect to binge drinking. Binge drinking as a habit was included to control for the fact that habitual drinking in social situations is hard to overcome and poses a particular challenge to interventions. The manipulation check showed that the experimental variation (sociable vs. unsociable drinker prototype condition) was successful. Results of the main study showed that the sociable drinker prototype condition resulted in a higher willingness and - for those with less of a habit - a higher intention to binge drink the next weekend. The unsociable drinker prototype condition had no effects. The results imply that the social components of mass media campaigns might inadvertently exacerbate binge drinking in young men. We therefore advocate against campaigns including aspects of alcohol consumption that might be positively associated with drinker prototype perception. Finally, we provide suggestions for future research.

Growth condition dependence of unintentional oxygen incorporation in epitaxial GaN.

Growth conditions have a tremendous impact on the unintentional background impurity concentration in gallium nitride (GaN) synthesized by molecular beam epitaxy and its resulting chemical and physical properties. In particular for oxygen identified as the dominant background impurity we demonstrate that under optimized growth stoichiometry the growth temperature is the key parameter to control its incorporation and that an increase by 55 °C leads to an oxygen reduction by one order of magnitude. Quantitatively this reduction and the resulting optical and electrical properties are analyzed by secondary ion mass spectroscopy, photoluminescence, capacitance versus voltage measurements, low temperature magneto-transport and parasitic current paths in lateral transistor test structures based on two-dimensional electron gases. At a growth temperature of 665 °C the residual charge carrier concentration is decreased to below 1015 cm-3, resulting in insulating behavior and thus making the material suitable for beyond state-of-the-art device applications.

The reciprocal internal/external frame of reference model using grades and test scores.

BACKGROUND: The reciprocal I/E model (RI/EM) combines the internal/external frame of reference model (I/EM) with the reciprocal effects model (REM). The RI/EM extends the I/EM longitudinally and the REM across domains. The model predicts that, within domains, mathematics and verbal achievement (VACH) and academic self-concept have positive effects on subsequent mathematics and VACH and academic self-concept within domains but have negative effects across domains. AIMS: The main purpose is to validate the RI/EM and extend it using objective achievement indicators and grades. SAMPLE: Two waves of data collection from grade 5 to grade 9 with N = 1,045 secondary school students were used. METHODS: Test scores, grades, and self-concept data were obtained. The main analyses were conducted using hierarchical linear modelling. RESULTS: The positive longitudinal effects of grades and test scores on subsequent grades, test scores and academic self-concept within domains and the negative effects of grades and test scores on subsequent academic self-concept across domains supported the RI/EM. The effects of academic self-concept on subsequent grades and test scores across domains were near zero when prior achievement indicators were controlled for. Overall, the results using school grades as achievement measures were replicated using standardized achievement test scores. CONCLUSIONS: The results serve to highlight the importance of the combination of common theories, which are mostly investigated individually, to enhance our understanding of the complexity of within- and across-domain relations between academic self-concepts and achievement using grades as well as test scores.

Gut microbiota-related modulation of immune mechanisms in post-infarction remodelling and heart failure.

The immune system has long been recognized as a key driver in the progression of heart failure (HF). However, clinical trials targeting immune effectors have consistently failed to improve patient outcome across different HF aetiologies. The activation of the immune system in HF is complex, involving a broad network of pro-inflammatory and immune-modulating components, which complicates the identification of specific immune pathways suitable for therapeutic targeting. Increasing attention has been devoted to identifying gut microbial pathways that affect cardiac remodelling and metabolism and, thereby impacting the development of HF. In particular, gut microbiota-derived metabolites, absorbed by the host and transported to the peripheral circulation, can act as signalling molecules, influencing metabolism and immune homeostasis. Recent reports suggest that the gut microbiota plays a crucial role in modulating immune processes involved in HF. Here, we summarize recent advances in understanding the contributory role of gut microbiota in (auto-)immune pathways that critically determine the progression or alleviation of HF. We also thoroughly discuss potential gut microbiota-based intervention strategies to treat or decelerate HF progression.

Modulation of the Serum Metabolome by the Short-Chain Fatty Acid Propionate: Potential Implications for Its Cholesterol-Lowering Effect.

(1) Background: Dyslipidemia represents a major risk factor for atherosclerosis-driven cardiovascular disease. Emerging evidence suggests a close relationship between cholesterol metabolism and gut microbiota. Recently, we demonstrated that the short-chain fatty acid (SCFA) propionate (PA) reduces serum cholesterol levels through an immunomodulatory mechanism. Here, we investigated the effects of oral PA supplementation on the human serum metabolome and analyzed changes in the serum metabolome in relation to the cholesterol-lowering properties of PA. (2) Methods: The serum metabolome of patients supplemented with either placebo or propionate orally for 8 weeks was assessed using a combination of flow injection analysis-tandem (FIA-MS/MS) as well as liquid chromatography (LC-MS/MS) and mass spectrometry using a targeted metabolomics kit (MxP®Quant 500 kit: BIOCRATES Life Sciences AG, Innsbruck, Austria). A total of 431 metabolites were employed for further investigation in this study. (3) Results: We observed a significant increase in distinct bile acids (GCDCA: fold change = 1.41, DCA: fold change = 1.39, GUDCA: fold change = 1.51) following PA supplementation over the study period, with the secondary bile acid DCA displaying a significant negative correlation with the serum cholesterol levels. (4) Conclusions: Oral supplementation with PA modulates the serum metabolome with a particular impact on the circulatory bile acid profile. Since cholesterol and bile acid metabolism are interconnected, the elevation of the secondary bile acid DCA may contribute to the cholesterol-lowering effect of PA.

Rapid Inflammasome Activation Is Attenuated in Post-Myocardial Infarction Monocytes.

Inflammasomes are crucial gatekeepers of the immune response, but their maladaptive activation associates with inflammatory pathologies. Besides canonical activation, monocytes can trigger non-transcriptional or rapid inflammasome activation that has not been well defined in the context of acute myocardial infarction (AMI). Rapid transcription-independent inflammasome activation induced by simultaneous TLR priming and triggering stimulus was measured by caspase-1 (CASP1) activity and interleukin release. Both classical and intermediate monocytes from healthy donors exhibited robust CASP1 activation, but only classical monocytes produced high mature interleukin-18 (IL18) release. We also recruited a limited number of coronary artery disease (CAD, n=31) and AMI (n=29) patients to evaluate their inflammasome function and expression profiles. Surprisingly, monocyte subpopulations isolated from blood collected during percutaneous coronary intervention (PCI) from AMI patients presented diminished CASP1 activity and abrogated IL18 release despite increased NLRP3 gene expression. This unexpected attenuated rapid inflammasome activation was accompanied by a significant increase of TNFAIP3 and IRAKM expression. Moreover, TNFAIP3 protein levels of circulating monocytes showed positive correlation with high sensitive troponin T (hsTnT), implying an association between TNFAIP3 upregulation and the severity of tissue injury. We suggest this monocyte attenuation to be a protective phenotype aftermath following a very early inflammatory wave in the ischemic area. Damage-associated molecular patterns (DAMPs) or other signals trigger a transitory negative feedback loop within newly recruited circulating monocytes as a mechanism to reduce post-injury tissue damage.

Do psychological variables mediate sex differences in young adults' alcohol use?

This study applied an extended theory of planned behavior to test whether psychological variables mediate sex differences in alcohol consumption in social contexts. Questionnaires of 300 young adults (urban, mean age 25 years, 49% female) were collected in 2007 prior to a sociable drinking occasion; consumption data were obtained through telephone interviews thereafter. The multiple-path mediation model was analyzed using structural equation modeling. Sex differences in alcohol consumption, which were considerable, were partly mediated by the significant specific indirect effects of subjective norms through intention and of self-efficacy through both intention and willingness. Body weight was not a significant mediator. Limitations are noted and implications for future research are discussed.

Externalizing behaviour, task-focused behaviour, and academic achievement: An indirect relation?

BACKGROUND: Although many studies have suggested that students' externalizing (aggressive and rule-breaking) behaviour is detrimental to their academic achievement, the underlying mechanisms have rarely been investigated. AIMS: We conducted a longitudinal investigation of whether the negative relation between externalizing behaviour and academic achievement operationalized as grades and test scores is mediated by students' task-focused behaviour while controlling for the effects of initial achievement and general cognitive abilities. We conducted separate analyses for different rating perspectives (i.e., parents and teachers) on students' externalizing behaviour to investigate the robustness of effects and determined whether gender moderated the mediation. SAMPLE: Participants were N = 1,039 students in 55 classes from different school types who were followed from fifth to ninth grade. METHOD: In fifth grade, parents and teachers rated students' externalizing behaviour, and students were administered standardized tests in mathematics, German, and general cognitive abilities. In seventh grade, teachers rated students' task-focused behaviour. In ninth grade, students were again administered standardized tests in mathematics and German, and their grades were obtained from school registries. RESULTS: Structural equation models consistently revealed indirect effects of externalizing behaviour via task-focused behaviour on grades and test scores beyond effects of initial achievement and general cognitive abilities. Result patterns were similar for parents' and teachers' ratings of externalizing behaviour and male and female students. CONCLUSIONS: This study extends knowledge about the negative relation between externalizing behaviour and academic achievement in adolescents by showing that there is an indirect relation through task-focused behaviour. Implications are discussed.

Preclinical assessment of a modified Occlutech left atrial appendage closure device in a porcine model.

Left atrial appendage (LAA) closure is being developed as an alternative for stroke prevention in patients with atrial fibrillation that cannot tolerate long-term oral anticoagulation. To assess the feasibility, safety, and performance of a novel modified Occlutech LAA closure device in a preclinical porcine model, the modified Occlutech modified Occlutech Plus LAA closure device was implanted in 12 female pigs (25-39 kg body weight) under fluoroscopic and transesophageal echocardiography (TEE) guidance. Procedural and technical success, as well as safety of LAA closure, were evaluated peri-procedurally and after 4, 8, and 12 weeks. Moreover, after 4, 8 and, 12 weeks animals were sacrificed for pathological analysis (e.g., thrombus formation, device ingrowth, endothelialization, and inflammation). All LAA closure devices were successfully implanted. On follow-up, no serious adverse events such as device-associated thrombus or translocalization/embolization were observed. A clinically non-significant pericarditis was observed in 4 animals at the time of autopsy. Endothelialization of the device was visible after 4 weeks, advanced after 8 weeks and completed after 12 weeks. Immunohistochemistry showed low amounts of inflammatory infiltration on the edges of the device. The results of this study indicate that implantation of a modified Occlutech LAA closure device is feasible with rapid endothelialization and low inflammatory infiltration in a porcine model. Human data are needed to further characterize safety and efficacy.

Young adults' social drinking as explained by an augmented theory of planned behaviour: the roles of prototypes, willingness, and gender.

OBJECTIVE: This study focused on young adults' alcohol consumption in social contexts. A dual-process model (including reasoned action and social reaction) was applied by combining the theory of planned behaviour (TPB) and the prototype/willingness model. A key question was whether willingness and actor and abstainer prototype variables would augment the TPB by increasing explained variance. DESIGN: Participants completed questionnaires prior to spending an evening socializing over the weekend (Time 1). Behavioural data were obtained by telephone interviews a few days after the social drinking occasion (Time 2). METHOD: N=300 people (mean age 25 years) took part in the study. The outcome measure of pure alcohol in grams was calculated based on participants' reports about their consumed drinks. Multigroup path analyses were conducted because of sex differences on behavioural and psychological variables. RESULTS: The TPB explained 35% of the variance in men's and 41% in women's alcohol consumption. Augmentation with prototype perception and willingness contributed significantly to the prediction of intention (DeltaR(2)=.07) and alcohol consumption for men (DeltaR(2)=.14). A significant interaction implied that willingness led to heavy drinking particularly among those men who made negative evaluations of the abstainer prototype. CONCLUSION: Women's alcohol consumption is explained by TPB variables via a more controlled reasoned-action path only, whereas additional processes (e.g., pursuing the actor image intentionally, rejecting the abstainer image more intuitively) are important for men. The moderating role of gender is discussed in light of traditional gender roles and recent trends in alcohol consumption.

An implicit neural familiar face identity recognition response across widely variable natural views in the human brain.

Highly variable natural images of the same familiar face celebrity interleaved periodically in a rapid (6 images/second) train of unfamiliar faces automatically elicit an objective electroencephalographic (EEG) response over the occipito-temporal cortex of neurotypical human adults within a few minutes. However, the extent to which this frequency-tagged response goes beyond the association of common physical features of the periodically repeated face identity remains unknown. Here we compare participants who know or do not know the very same periodically repeated face celebrity and show that long-term familiarity accounts for about 80% of the neural face identity recognition response. This familiarity advantage disappears with upside-down images. Variability in response amplitude between face identities is preserved for inverted faces and in unfamiliar participants, suggesting a contribution of within-person physical face variability and distinctiveness to about 20% of the face identity response. These observations provide the strongest difference to date in human brain response between the same famous face identities perceived as familiar or unfamiliar in an implicit task. The frequency-tagged neural response largely reflects the strengthening effect of long-term memory in the human occipito-temporal cortex, and may serve to index automatic familiar face identity recognition in individual observers.

Impact of the Gut Microbiota on Atorvastatin Mediated Effects on Blood Lipids.

BACKGROUND AND AIMS: The mechanisms of interindividual variation of lipid regulation by statins, such as the low-density lipoprotein cholesterol (LDL) lowering effects, are not fully understood yet. Here, we used a gut microbiota depleted mouse model to investigate the relation between the gut microbiota and the regulatory property of atorvastatin on blood lipids. METHODS: Mice (C57BL/6) with intact gut microbiota or antibiotic induced abiotic mice (ABS) were put on standard chow diet (SCD) or high fat diet (HFD) for six weeks. Atorvastatin (10 mg/kg body weight/day) or a control vehicle were applied per gavage for the last four weeks of dietary treatment. Blood lipids including total cholesterol, very low-density lipoprotein, low-density lipoprotein, high-density lipoprotein and sphingolipids were measured to probe microbiota-dependent effects of atorvastatin. The expression of genes involved in hepatic and intestinal cholesterol metabolism was analyzed with qRT-PCR. The alteration of the microbiota profile was examined using 16S rRNA qPCR in mice with intact gut microbiota. RESULTS: HFD feeding significantly increased total blood cholesterol and LDL levels, as compared to SCD in both mice with intact and depleted gut microbiota. The cholesterol lowering effect of atorvastatin was significantly attenuated in mice with depleted gut microbiota. Moreover, we observed a global shift in the abundance of several sphingolipids upon atorvastatin treatment which was absent in gut microbiota depleted mice. The regulatory effect of atorvastatin on the expression of distinct hepatic and intestinal cholesterol-regulating genes, including Ldlr, Srebp2 and Npc1l1 was altered upon depletion of gut microbiota. In response to HFD feeding, the relative abundance of the bacterial phyla Bacteroidetes decreased, while the abundance of Firmicutes increased. The altered ratio between Firmicutes to Bacteroidetes was partly reversed in HFD fed mice treated with atorvastatin. CONCLUSIONS: Our findings support a regulatory impact of atorvastatin on the gut microbial profile and, in turn, demonstrate a crucial role of the gut microbiome for atorvastatin-related effects on blood lipids. These results provide novel insights into potential microbiota-dependent mechanisms of lipid regulation by statins, which may account for variable response to statin treatment.

Factors associated with health-related quality of life, anxiety and depression among young adults with epilepsy and mild cognitive impairments in short-term residential care.

INTRODUCTION: This study examined associations of health-related quality of life (HRQOL), anxiety, and depression with medical and psychosocial variables. Participants were young adults with epilepsy and additional mild cognitive impairments in short-term residential care of the Bethel Institute, Germany. METHODS: Thirty-six individuals were interviewed using the Quality of Life in Epilepsy Inventory 31 (QOLIE-31), the Hospital Anxiety and Depression Scale (HADS) and the neuroticism scale of the Neo-Five-Factor Inventory (NEO-FFI). Medical as well as socio-demographic data were assembled from client files. RESULTS: Regression analyses revealed neuroticism as the strongest predictor of HRQOL, anxiety and depression. The only variables that additionally explained a substantial proportion of variance counting for 6-10% in the three criteria were age at epilepsy onset and sex: epilepsy onset after the age of 10 years was associated with lower HRQOL and higher anxiety, men suffered from more depression than women. DISCUSSION: Neuroticism as a personality disposition seems to be most influential on HRQOL and anxiety in people with epilepsy and mild cognitive impairment. The impact of sex and age at epilepsy onset on HRQOL, anxiety and depression of this epilepsy subpopulation should be further clarified.

An objective, sensitive and ecologically valid neural measure of rapid human individual face recognition.

Humans may be the only species able to rapidly and automatically recognize a familiar face identity in a crowd of unfamiliar faces, an important social skill. Here, by combining electroencephalography (EEG) and fast periodic visual stimulation (FPVS), we introduce an ecologically valid, objective and sensitive neural measure of this human individual face recognition function. Natural images of various unfamiliar faces are presented at a fast rate of 6 Hz, allowing one fixation per face, with variable natural images of a highly familiar face identity, a celebrity, appearing every seven images (0.86 Hz). Following a few minutes of stimulation, a high signal-to-noise ratio neural response reflecting the generalized discrimination of the familiar face identity from unfamiliar faces is observed over the occipito-temporal cortex at 0.86 Hz and harmonics. When face images are presented upside-down, the individual familiar face recognition response is negligible, being reduced by a factor of 5 over occipito-temporal regions. Differences in the magnitude of the individual face recognition response across different familiar face identities suggest that factors such as exposure, within-person variability and distinctiveness mediate this response. Our findings of a biological marker for fast and automatic recognition of individual familiar faces with ecological stimuli open an avenue for understanding this function, its development and neural basis in neurotypical individual brains along with its pathology. This should also have implications for the use of facial recognition measures in forensic science.

Self-proxy agreement and correlates of health-related quality of life in young adults with epilepsy and mild intellectual disabilities.

This study investigated health-related quality of life (HRQOL) in young adults with epilepsy and intellectual disabilities. First, agreement between self-reports and proxy reports of HRQOL was examined. Second, medical and psychological contributions to HRQOL were explored. Thirty-six patients were interviewed using the Quality of Life in Epilepsy inventory (QOLIE-31), the Hospital Anxiety and Depression Scale, and the Neuroticism and Extraversion scales of the NEO Five-Factor Inventory. Medical data were taken from files. Professional caregivers completed rephrased QOLIE-31-questionnaires. The perspectives on HRQOL differed systematically: Caregivers underrated their clients' HRQOL on average. Few correlations with medical characteristics emerged, whereas all psychological variables were strongly related to HRQOL. Neuroticism, Age at Disability Onset, and their interaction explained 71% of the HRQOL variance. Results indicate that proxy reports do not provide valid substitutes for most of the self-reported HRQOL subscales. Psychological treatment of negative affectivity and after critical life events in adolescence may improve HRQOL in young adults with epilepsy and mild intellectual disabilities.