Managing psychogenic pseudosyncope: Facts and experiences

Psychogenic pseudosyncope (PPS) is a common cause of apparent transient loss of conscious­ness (TLOC) with a dramatic impact on the quality of life. This review aims to give an overview of the definition, incidence, etiology, diagnosis, treatment, and prognosis of PPS based on a combination of literature data and personal experience. The limited literature on the subject suggests that PPS is relatively common but insufficiently recognized. PPS is probably similar to psychogenic nonepiteptic seizures (PNES), in which a long delay to diagnosis worsens the prognosis. A detailed history is of paramount importance for the diagnosis. The key feature in the history of patients with PPS is the occurrence of frequent, long attacks of apparent TLOC with closed eyes. The diagnosis is certain when a typical event is recorded during a tilt-table test with simultaneous blood pressure (BP), heart rate and video-electroencephalographic re­cordings. Home video and BP recording during an attack can be very useful. The diagnosis should be communicated to the patient in a way that is clear, understandable and does not cause offense. Although treatment options have not been investigated formally, the literature on PNES suggests that cognitive behavioral therapy is beneficial

Are the orthostatic fluid shifts to the calves augmented in autonomic failure?

In autonomic failure (AF), blood pressure (BP) falls upon standing which is commonly ascribed to defective vasoconstriction and excessive pooling. Observations on the amount of pooling in AF are contradictory. We evaluated pooling using strain-gauge plethysmography (SGP) during head-up tilt (HUT) with a parachute harness fixed to the tilt table to avoid muscle tension in the lower limbs and thus to maximise pooling. 23 healthy subjects and 12 patients with AF were tilted for 5 min. BP and calf volume changes, as measured by SGP, were measured continuously. Multiple regression analysis was used to examine the effect of AF on orthostatic fluid shifts after adjustment for potential confounders. Patients did not differ from controls with respect to the increase of calf volume after 5 min HUT. The acute (0-1 min) and the prolonged (1-5 min) phases of calf volume responses to HUT were also similar between patients and controls. No correlation was found between the degree of orthostatic hypotension and the orthostatic calf volume change in AF. In one patient an additional measurement was made before rising from bed in the early morning demonstrating a greater albeit small increase of calf volume upon HUT. Orthostatic fluid shifts at the level of the calf in AF are not augmented during the course of the day despite marked hypotension. However, a small increase of pooling may be expected when the patient first gets out of bed in the morning probably due to the absence of oedema.Paroxysmal Cerebral Disorder

A novel approach to identifying regulatory motifs in distantly related genomes

Although proven successful in the identification of regulatory motifs, phylogenetic footprinting methods still show some shortcomings. To assess these difficulties, most apparent when applying phylogenetic footprinting to distantly related organisms, we developed a two-step procedure that combines the advantages of sequence alignment and motif detection approaches. The results on well-studied benchmark datasets indicate that the presented method outperforms other methods when the sequences become either too long or too heterogeneous in size

TOUCAN 2: the all-inclusive open source workbench for regulatory sequence analysis

We present the second and improved release of the TOUCAN workbench for cis-regulatory sequence analysis. TOUCAN implements and integrates fast state-of-the-art methods and strategies in gene regulation bioinformatics, including algorithms for comparative genomics and for the detection of cis-regulatory modules. This second release of TOUCAN has become open source and thereby carries the potential to evolve rapidly. The main goal of TOUCAN is to allow a user to come to testable hypotheses regarding the regulation of a gene or of a set of co-regulated genes. TOUCAN can be launched from this location:

More robust detection of motifs in coexpressed genes by using phylogenetic information

BACKGROUND: Several motif detection algorithms have been developed to discover overrepresented motifs in sets of coexpressed genes. However, in a noisy gene list, the number of genes containing the motif versus the number lacking the motif might not be sufficiently high to allow detection by classical motif detection tools. To still recover motifs which are not significantly enriched but still present, we developed a procedure in which we use phylogenetic footprinting to first delineate all potential motifs in each gene. Then we mutually compare all detected motifs and identify the ones that are shared by at least a few genes in the data set as potential candidates. RESULTS: We applied our methodology to a compiled test data set containing known regulatory motifs and to two biological data sets derived from genome wide expression studies. By executing four consecutive steps of 1) identifying conserved regions in orthologous intergenic regions, 2) aligning these conserved regions, 3) clustering the conserved regions containing similar regulatory regions followed by extraction of the regulatory motifs and 4) screening the input intergenic sequences with detected regulatory motif models, our methodology proves to be a powerful tool for detecting regulatory motifs when a low signal to noise ratio is present in the input data set. Comparing our results with two other motif detection algorithms points out the robustness of our algorithm. CONCLUSION: We developed an approach that can reliably identify multiple regulatory motifs lacking a high degree of overrepresentation in a set of coexpressed genes (motifs belonging to sparsely connected hubs in the regulatory network) by exploiting the advantages of using both coexpression and phylogenetic information

In silico identification and experimental validation of PmrAB targets in Salmonella typhimurium by regulatory motif detection

BACKGROUND: The PmrAB (BasSR) two-component regulatory system is required for Salmonella typhimurium virulence. PmrAB-controlled modifications of the lipopolysaccharide (LPS) layer confer resistance to cationic antibiotic polypeptides, which may allow bacteria to survive within macrophages. The PmrAB system also confers resistance to Fe(3+)-mediated killing. New targets of the system have recently been discovered that seem not to have a role in the well-described functions of PmrAB, suggesting that the PmrAB-dependent regulon might contain additional, unidentified targets. RESULTS: We performed an in silico analysis of possible targets of the PmrAB system. Using a motif model of the PmrA binding site in DNA, genome-wide screening was carried out to detect PmrAB target genes. To increase confidence in the predictions, all putative targets were subjected to a cross-species comparison (phylogenetic footprinting) using a Gibbs sampling-based motif-detection procedure. As well as the known targets, we detected additional targets with unknown functions. Four of these were experimentally validated (yibD, aroQ, mig-13 and sseJ). Site-directed mutagenesis of the PmrA-binding site (PmrA box) in yibD revealed specific sequence requirements. CONCLUSIONS: We demonstrated the efficiency of our procedure by recovering most of the known PmrAB-dependent targets and by identifying unknown targets that we were able to validate experimentally. We also pinpointed directions for further research that could help elucidate the S. typhimurium virulence pathway

Variability of cardioinhibition in vasovagal syncope:differences between subgroups during cardioinhibition and beyond

Purpose: We compared hemodynamic parameters between subjects with marked, intermediate and minimal cardioinhibition during vasovagal syncope.Methods: The study included subjects with a decrease in heart rate while experiencing a complete vasovagal syncope during tilt-table testing. The subjects were classified as having marked, intermediate or minimal cardioinhibition, based on tertile values of the decrease in heart rate. Hemodynamic parameters between these groups were compared before tilt in the supine position, shortly after tilt and during cardioinhibition. Results:A total of 149 subjects with a median age of 43 (interquartile range 24–60) years were included in the study. Among the three groups with different levels of cardioinhibition, the highest heart rate was observed in subjects with marked cardioinhibition both before and shortly after tilt and at the start of cardioinhibition. The heart rate decrease in these subjects was both larger and faster compared to subjects with minimal and intermediate cardioinhibition. Conclusion: Subjects with marked cardioinhibition have both a larger and faster decrease in heart rate compared to subjects with intermediate and minimal cardioinhibition, as early as from the start of cardioinhibition. Marked cardioinhibition is related to differences in hemodynamic profiles already present well before the start of cardioinhibition.</p

Low lopinavir plasma or hair concentrations explain second-line protease inhibitor failures in a resource-limited setting.

In resource-limited settings, many patients, with no prior protease inhibitor (PI) treatment on a second-line, high genetic barrier, ritonavir-boosted PI-containing regimen have virologic failure

Growing Up Together in Society (GUTS):A team science effort to predict societal trajectories in adolescence and young adulthood

Our society faces a great diversity of opportunities for youth. The 10-year Growing Up Together in Society (GUTS) program has the long-term goal to understand which combination of measures best predict societal trajectories, such as school success, mental health, well-being, and developing a sense of belonging in society. Our leading hypothesis is that self-regulation is key to how adolescents successfully navigate the demands of contemporary society. We aim to test these questions using socio-economic, questionnaire (including experience sampling methods), behavioral, brain (fMRI, sMRI, EEG), hormonal, and genetic measures in four large cohorts including adolescents and young adults. Two cohorts are designed as test and replication cohorts to test the developmental trajectory of self-regulation, including adolescents of different socioeconomic status thereby bridging individual, family, and societal perspectives. The third cohort consists of an entire social network to examine how neural and self-regulatory development influences and is influenced by whom adolescents and young adults choose to interact with. The fourth cohort includes youth with early signs of antisocial and delinquent behavior to understand patterns of societal development in individuals at the extreme ends of self-regulation and societal participation, and examines pathways into and out of delinquency. We will complement the newly collected cohorts with data from existing large-scale population-based and case-control cohorts. The study is embedded in a transdisciplinary approach that engages stakeholders throughout the design stage, with a strong focus on citizen science and youth participation in study design, data collection, and interpretation of results, to ensure optimal translation to youth in society.</p

Growing Up Together in Society (GUTS):A team science effort to predict societal trajectories in adolescence and young adulthood

Our society faces a great diversity of opportunities for youth. The 10-year Growing Up Together in Society (GUTS) program has the long-term goal to understand which combination of measures best predict societal trajectories, such as school success, mental health, well-being, and developing a sense of belonging in society. Our leading hypothesis is that self-regulation is key to how adolescents successfully navigate the demands of contemporary society. We aim to test these questions using socio-economic, questionnaire (including experience sampling methods), behavioral, brain (fMRI, sMRI, EEG), hormonal, and genetic measures in four large cohorts including adolescents and young adults. Two cohorts are designed as test and replication cohorts to test the developmental trajectory of self-regulation, including adolescents of different socioeconomic status thereby bridging individual, family, and societal perspectives. The third cohort consists of an entire social network to examine how neural and self-regulatory development influences and is influenced by whom adolescents and young adults choose to interact with. The fourth cohort includes youth with early signs of antisocial and delinquent behavior to understand patterns of societal development in individuals at the extreme ends of self-regulation and societal participation, and examines pathways into and out of delinquency. We will complement the newly collected cohorts with data from existing large-scale population-based and case-control cohorts. The study is embedded in a transdisciplinary approach that engages stakeholders throughout the design stage, with a strong focus on citizen science and youth participation in study design, data collection, and interpretation of results, to ensure optimal translation to youth in society.</p