Negative Emotional Stimuli Enhance Vestibular Processing

Recent studies have shown that vestibular stimulation can influence affective processes. In the present study, we examined whether emotional information can also modulate vestibular perception. Participants performed a vestibular discrimination task on a motion platform while viewing emotional pictures. Six different picture categories were taken from the International Affective Picture System: mutilation, threat, snakes, neutral objects, sports, and erotic pictures. Using a Bayesian hierarchical approach, we were able to show that vestibular discrimination improved when participants viewed emotionally negative pictures (mutilation, threat, snake) when compared to neutral/positive objects. We conclude that some of the mechanisms involved in the processing of vestibular information are also sensitive to emotional content. Emotional information signals importance and mobilizes the body for action. In case of danger, a successful motor response requires precise vestibular processing. Therefore, negative emotional information improves processing of vestibular information.

Street crossing behavior in younger and older pedestrians: an eye- and head-tracking study

BACKGROUND: Crossing a street can be a very difficult task for older pedestrians. With increased age and potential cognitive decline, older people take the decision to cross a street primarily based on vehicles' distance, and not on their speed. Furthermore, older pedestrians tend to overestimate their own walking speed, and could not adapt it according to the traffic conditions. Pedestrians' behavior is often tested using virtual reality. Virtual reality presents the advantage of being safe, cost-effective, and allows using standardized test conditions. METHODS: This paper describes an observational study with older and younger adults. Street crossing behavior was investigated in 18 healthy, younger and 18 older subjects by using a virtual reality setting. The aim of the study was to measure behavioral data (such as eye and head movements) and to assess how the two age groups differ in terms of number of safe street crossings, virtual crashes, and missed street crossing opportunities. Street crossing behavior, eye and head movements, in older and younger subjects, were compared with non-parametric tests. RESULTS: The results showed that younger pedestrians behaved in a more secure manner while crossing a street, as compared to older people. The eye and head movements analysis revealed that older people looked more at the ground and less at the other side of the street to cross. CONCLUSIONS: The less secure behavior in street crossing found in older pedestrians could be explained by their reduced cognitive and visual abilities, which, in turn, resulted in difficulties in the decision-making process, especially under time pressure. Decisions to cross a street are based on the distance of the oncoming cars, rather than their speed, for both groups. Older pedestrians look more at their feet, probably because of their need of more time to plan precise stepping movement and, in turn, pay less attention to the traffic. This might help to set up guidelines for improving senior pedestrians' safety, in terms of speed limits, road design, and mixed physical-cognitive trainings.

The distinction between real and fictional worlds: Investigating individual differences in fantasy understanding

In this paper, two studies are reported in which children’s ability to distinguish reality from fantasy was investigated. In Experiment 1, children of different ages made pairwise comparisons of 12 pictures of fictional figures and 3 photographs of real people by evaluating on a 6-point scale how easily these figures could meet each other. The results revealed that fantasy/reality distinction develops with age: 7–8-year-old showed a fundamental categorical distinction (comparable to that of adults) whereas 3–4-year-old treated the real world like one of many worlds. In Experiment 2, we took an individual differences approach and tested 116 4–5-year-old who performed the same fantasy task. In addition, they were presented with theory-of-mind tasks and tests measuring non-verbal intelligence and language skills. The results showed that, after statistically controlling for age, non-verbal intelligence, and language skills, theory-of-mind abilities still significantly contributed to the prediction of fantasy understanding.

When looking back to nothing goes back to nothing

Previous research showed that the eyes revisit the location in which the stimulus has been encoded when visual or verbal information is retrieved from memory. A recent study showed that this behavior still occurs 1 week after encoding, suggesting that visual, spatial and linguistic information is tightly associated with the oculomotor trace and stored as an integrated memory representation. However, it is yet unclear whether looking behavior simply remains stable between encoding and recall or whether it changes over time in a more fine-tuned manner. Here, we investigate the time course of looking behavior during recall in multiple sessions across 1 week. Participants encoded visual objects presented in one of the four locations on the computer screen. In five sessions during the week after encoding, they performed on a visual memory recall task. During retrieval, participants looked back to the encoding location, but only in the recall sessions within 1 day of encoding. We discuss different explanations for the temporal dynamics of looking behavior during recall, searching for the role of eye movements in memory.

Inactive Matrix Gla-Protein Is Associated With Arterial Stiffness in an Adult Population-Based Study

Increased pulse wave velocity (PWV) is a marker of aortic stiffness and an independent predictor of mortality. Matrix Gla-protein (MGP) is a vascular calcification inhibitor that needs vitamin K to be activated. Inactive MGP, known as desphospho-uncarboxylated MGP (dp-ucMGP), can be measured in plasma and has been associated with various cardiovascular markers, cardiovascular outcomes, and mortality. In this study, we hypothesized that high levels of dp-ucMGP are associated with increased PWV. We recruited participants via a multicenter family-based cross-sectional study in Switzerland. Dp-ucMGP was quantified in plasma by sandwich ELISA. Aortic PWV was determined by applanation tonometry using carotid and femoral pulse waveforms. Multiple regression analysis was performed to estimate associations between PWV and dp-ucMGP adjusting for age, renal function, and other cardiovascular risk factors. We included 1001 participants in our analyses (475 men and 526 women). Mean values were 7.87±2.10 m/s for PWV and 0.43±0.20 nmol/L for dp-ucMGP. PWV was positively associated with dp-ucMGP both before and after adjustment for sex, age, body mass index, height, systolic and diastolic blood pressure (BP), heart rate, renal function, low- and high-density lipoprotein, glucose, smoking status, diabetes mellitus, BP and cholesterol lowering drugs, and history of cardiovascular disease (P≤0.01). In conclusion, high levels of dp-ucMGP are independently and positively associated with arterial stiffness after adjustment for common cardiovascular risk factors, renal function, and age. Experimental studies are needed to determine whether vitamin K supplementation slows arterial stiffening by increasing MGP carboxylation.

Heritability of ambulatory and office blood pressure in the Swiss population

BACKGROUND Blood pressure (BP) is known to aggregate in families. Yet, heritability estimates are population-specific and no Swiss data have been published so far. We estimated the heritability of ambulatory and office BP in a Swiss population-based sample. METHODS The Swiss Kidney Project on Genes in Hypertension is a population-based family study focusing on BP genetics. Office and ambulatory BP were measured in 1009 individuals from 271 nuclear families. Heritability was estimated for SBP, DBP, and pulse pressure using a maximum likelihood method implanted in the Statistical Analysis in Genetic Epidemiology software. RESULTS The 518 women and 491 men included in this analysis had a mean (±SD) age of 48.3 (±17.4) and 47.3 (±17.7) years, and a mean BMI of 23.8 (±4.2) and 25.9 (±4.1) kg/m, respectively. Narrow-sense heritability estimates (±standard error) for ambulatory SBP, DBP, and pulse pressure were 0.37 ± 0.07, 0.26 ± 0.07, and 0.29 ± 0.07 for 24-h BP; 0.39 ± 0.07, 0.28 ± 0.07, and 0.27 ± 0.07 for day BP; and 0.25 ± 0.07, 0.20 ± 0.07, and 0.30 ± 0.07 for night BP, respectively (all P < 0.001). Heritability estimates for office SBP, DBP, and pulse pressure were 0.21 ± 0.08, 0.25 ± 0.08, and 0.18 ± 0.07 (all P < 0.01). CONCLUSIONS We found significant heritability estimates for both ambulatory and office BP in this Swiss population-based study. Our findings justify the ongoing search for the genetic determinants of BP.

CYP17A1 Enzyme Activity Is Linked to Ambulatory Blood Pressure in a Family-Based Population Study

BACKGROUND Genome-wide association studies have linked CYP17A1 coding for the steroid hormone synthesizing enzyme 17α-hydroxylase (CYP17A1) to blood pressure (BP). We hypothesized that the genetic signal may translate into a correlation of ambulatory BP (ABP) with apparent CYP17A1 activity in a family-based population study and estimated the heritability of CYP17A1 activity. METHODS In the Swiss Kidney Project on Genes in Hypertension, day and night urinary excretions of steroid hormone metabolites were measured in 518 participants (220 men, 298 women), randomly selected from the general population. CYP17A1 activity was assessed by 2 ratios of urinary steroid metabolites: one estimating the combined 17α-hydroxylase/17,20-lyase activity (ratio 1) and the other predominantly 17α-hydroxylase activity (ratio 2). A mixed linear model was used to investigate the association of ABP with log-transformed CYP17A1 activities exploring effect modification by urinary sodium excretion. RESULTS Daytime ABP was positively associated with ratio 1 under conditions of high, but not low urinary sodium excretion (P interaction <0.05). Ratio 2 was not associated with ABP. Heritability estimates (SE) for day and night CYP17A1 activities were 0.39 (0.10) and 0.40 (0.09) for ratio 1, and 0.71 (0.09) and 0.55 (0.09) for ratio 2 (P values <0.001). CYP17A1 activities, assessed with ratio 1, were lower in older participants. CONCLUSIONS Low apparent CYP17A1 activity (assessed with ratio 1) is associated with elevated daytime ABP when salt intake is high. CYP17A1 activity is heritable and diminished in the elderly. These observations highlight the modifying effect of salt intake on the association of CYP17A1 with BP.

Associations of Urinary Uromodulin with Clinical Characteristics and Markers of Tubular Function in the General Population

BACKGROUND AND OBJECTIVES Allelic variants in UMOD, the gene coding for uromodulin, are associated with rare tubulointerstitial kidney disorders and risk of CKD and hypertension in the general population. The factors associated with uromodulin excretion in the normal population remain largely unknown, and were therefore explored in this study. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Urinary uromodulin excretion was measured using a validated ELISA in two population-based cohorts that included more than 6500 individuals. The Swiss Kidney Project on Genes in Hypertension study (SKIPOGH) included 817 adults (mean age±SD, 45±17 years) who underwent renal ultrasonography and performed a 24-hour urine collection. The Cohorte Lausannoise study included 5706 adults (mean age, 53±11 years) with fresh spot morning urine samples. We calculated eGFRs using the CKD-Epidemiology Collaboration formula and by 24-hour creatinine clearance. RESULTS In both studies, positive associations were found between uromodulin and urinary sodium, chloride, and potassium excretion and osmolality. In SKIPOGH, 24-hour uromodulin excretion (median, 41 [interquartile range, 29-57] mg/24 h) was positively associated with kidney length and volume and with creatinine excretion and urine volume. It was negatively associated with age and diabetes. Both spot uromodulin concentration and 24-hour uromodulin excretion were linearly and positively associated (multivariate analyses) with eGFR<90 ml/min per 1.73 m(2). CONCLUSION Age, creatinine excretion, diabetes, and urinary volume are independent clinical correlates of urinary uromodulin excretion. The associations of uromodulin excretion with markers of tubular functions and kidney dimensions suggest that it may reflect tubule activity in the general population.

Disrupting frontal eye-field activity impairs memory recall

A large body of research demonstrated that participants preferably look back to the encoding location when retrieving visual information from memory. However, the role of this 'looking back to nothing' is still debated. The goal of the present study was to extend this line of research by examining whether an important area in the cortical representation of the oculomotor system, the frontal eye field (FEF), is involved in memory retrieval. To interfere with the activity of the FEF, we used inhibitory continuous theta burst stimulation (cTBS). Before stimulation was applied, participants encoded a complex scene and performed a short-term (immediately after encoding) or long-term (after 24 h) recall task, just after cTBS over the right FEF or sham stimulation. cTBS did not affect overall performance, but stimulation and statement type (object vs. location) interacted. cTBS over the right FEF tended to impair object recall sensitivity, whereas there was no effect on location recall sensitivity. These findings suggest that the FEF is involved in retrieving object information from scene memory, supporting the hypothesis that the oculomotor system contributes to memory recall.

Self-motion direction discrimination in the visually impaired

Despite the close interrelation between vestibular and visual processing (e.g., vestibulo-ocular reflex), surprisingly little is known about vestibular function in visually impaired people. In this study, we investigated thresholds of passive whole-body motion discrimination (leftward vs. rightward) in nine visually impaired participants and nine age-matched sighted controls. Participants were rotated in yaw, tilted in roll, and translated along the interaural axis at two different frequencies (0.33 and 2 Hz) by means of a motion platform. Superior performance of visually impaired participants was found in the 0.33 Hz roll tilt condition. No differences were observed in the other motion conditions. Roll tilts stimulate the semicircular canals and otoliths simultaneously. The results could thus reflect a specific improvement in canal–otolith integration in the visually impaired and are consistent with the compensatory hypothesis, which implies that the visually impaired are able to compensate the absence of visual input.

TrypanoCyc: a community-led biochemical pathways database for Trypanosoma brucei.

The metabolic network of a cell represents the catabolic and anabolic reactions that interconvert small molecules (metabolites) through the activity of enzymes, transporters and non-catalyzed chemical reactions. Our understanding of individual metabolic networks is increasing as we learn more about the enzymes that are active in particular cells under particular conditions and as technologies advance to allow detailed measurements of the cellular metabolome. Metabolic network databases are of increasing importance in allowing us to contextualise data sets emerging from transcriptomic, proteomic and metabolomic experiments. Here we present a dynamic database, TrypanoCyc (http://www.metexplore.fr/trypanocyc/), which describes the generic and condition-specific metabolic network of Trypanosoma brucei, a parasitic protozoan responsible for human and animal African trypanosomiasis. In addition to enabling navigation through the BioCyc-based TrypanoCyc interface, we have also implemented a network-based representation of the information through MetExplore, yielding a novel environment in which to visualise the metabolism of this important parasite.

How to prevent overdiagnosis.

Overdiagnosis is the diagnosis of an abnormality that is not associated with a substantial health hazard and that patients have no benefit to be aware of. It is neither a misdiagnosis (diagnostic error), nor a false positive result (positive test in the absence of a real abnormality). It mainly results from screening, use of increasingly sensitive diagnostic tests, incidental findings on routine examinations, and widening diagnostic criteria to define a condition requiring an intervention. The blurring boundaries between risk and disease, physicians' fear of missing a diagnosis and patients' need for reassurance are further causes of overdiagnosis. Overdiagnosis often implies procedures to confirm or exclude the presence of the condition and is by definition associated with useless treatments and interventions, generating harm and costs without any benefit. Overdiagnosis also diverts healthcare professionals from caring about other health issues. Preventing overdiagnosis requires increasing awareness of healthcare professionals and patients about its occurrence, the avoidance of unnecessary and untargeted diagnostic tests, and the avoidance of screening without demonstrated benefits. Furthermore, accounting systematically for the harms and benefits of screening and diagnostic tests and determining risk factor thresholds based on the expected absolute risk reduction would also help prevent overdiagnosis.

Entwicklung und Implementierung eines Wort-Bild Trainings zur Förderung der Lesefertigkeiten bei Lernschwierigkeiten und / oder onkologischen Erkrankungen des Zentralnervensystems

Neurokognitive Spätfolgen nach pädiatrischem Hirntumor spielen bei der immer grösser werdenden Anzahl von Überlebenden eine wichtige Rolle. Im Bereich der schulischen Fertigkeiten zeigen sich vor allem Defizite in der Lesekompetenz. Die Hauptziele der vorliegenden Studien bestanden darin, Hirnfunktionsstörungen bei einer ausgewählten Gruppe von Kindern und Jugendlichen (Hirntumorpatienten) zum Zeitpunkt der Diagnose zu erfassen, sowie Wissen über alters- und intelligenzunabhängige Einflussmöglichkeiten auf die kognitive Leistung am Beispiel des Lesens bereitzustellen. Insgesamt flossen Daten von rund 180 Kindern und Jugendlichen in die jeweiligen Analysen ein, wobei sowohl ein klinisches Sample (Kinder und Jugendliche mit Krebserkrankungen) als auch Kinder aus unterschiedlichen Altersgruppen und in zwei verschiedenen Schulmodellen (Primarschule und Heilpädagogische Schule) berücksichtigt wurden. Zusammenfassend kann gesagt werden, dass Krebserkrankungen, welche das zentrale Nervensystem betreffen, schon zum Zeitpunkt der Diagnose Auswirkungen auf basale neurokognitive Fähigkeiten haben. Diese Defizite können zu einer Verzögerung der neurokognitiven Entwicklung beitragen. Daher müssen möglichst früh pädagogische und/oder therapeutische Massnahmen eingeleitet werden, welche in den Patienten- und Schulalltag implementiert werden können. Das hier vorgestellte neu entwickelte Wort-Bild-Training, das in einem ersten Schritt bei normalbegabten und geistig behinderten Kindern verschiedener Altersstufen positive Effekte auf die Verbesserung der Lesefertigkeit und des Leseverständnisses gezeigt hat, könnte ebenfalls eine wertvolle Fördermöglichkeit für Kinder mit Hirnfunktionsstörungen aufgrund onkologischer Erkrankungen darstellen. Obwohl die erreichte Verbesserung der Lesekompetenz eher klein ausfiel, wiesen die Effekte zumindest über kurze Zeit eine gewisse Stabilität auf. Dieser Befund spricht für die Möglichkeit der Einflussnahme auf die Leseprozesse durch das (auf implizitem statistischen Lernen basierende) Training, widerspiegelt gleichzeitig aber auch deren Grenzen. Das gewonnene Wissen wird in Bezug auf die Relevanz für die klinische und pädagogische Praxis diskutiert. Ausgehend von den eigenen Studienergebnissen wird schliesslich angeregt, impliziten Lernstrategien in den Lehrplänen einen höheren Stellenwert einzuräumen und mit der Förderung von einfachen Lesestrategien bei pädiatrischen Hirntumorpatienten möglichst frühzeitig zu beginnen.

Sociodemographic, behavioral and genetic determinants of allostatic load in a Swiss population-based study.

Allostatic load (AL) is a marker of physiological dysregulation which reflects exposure to chronic stress. High AL has been related to poorer health outcomes including mortality. We examine here the association of socioeconomic and lifestyle factors with AL. Additionally, we investigate the extent to which AL is genetically determined. We included 803 participants (52% women, mean age 48±16years) from a population and family-based Swiss study. We computed an AL index aggregating 14 markers from cardiovascular, metabolic, lipidic, oxidative, hypothalamus-pituitary-adrenal and inflammatory homeostatic axes. Education and occupational position were used as indicators of socioeconomic status. Marital status, stress, alcohol intake, smoking, dietary patterns and physical activity were considered as lifestyle factors. Heritability of AL was estimated by maximum likelihood. Women with a low occupational position had higher AL (low vs. high OR=3.99, 95%CI [1.22;13.05]), while the opposite was observed for men (middle vs. high OR=0.48, 95%CI [0.23;0.99]). Education tended to be inversely associated with AL in both sexes(low vs. high OR=3.54, 95%CI [1.69;7.4]/OR=1.59, 95%CI [0.88;2.90] in women/men). Heavy drinking men as well as women abstaining from alcohol had higher AL than moderate drinkers. Physical activity was protective against AL while high salt intake was related to increased AL risk. The heritability of AL was estimated to be 29.5% ±7.9%. Our results suggest that generalized physiological dysregulation, as measured by AL, is determined by both environmental and genetic factors. The genetic contribution to AL remains modest when compared to the environmental component, which explains approximately 70% of the phenotypic variance.