Prediction of sarcomere mutations in subclinical hypertrophic cardiomyopathy.

BACKGROUND: Sarcomere protein mutations in hypertrophic cardiomyopathy induce subtle cardiac structural changes before the development of left ventricular hypertrophy (LVH). We have proposed that myocardial crypts are part of this phenotype and independently associated with the presence of sarcomere gene mutations. We tested this hypothesis in genetic hypertrophic cardiomyopathy pre-LVH (genotype positive, LVH negative [G+LVH-]). METHODS AND RESULTS: A multicenter case-control study investigated crypts and 22 other cardiovascular magnetic resonance parameters in subclinical hypertrophic cardiomyopathy to determine their strength of association with sarcomere gene mutation carriage. The G+LVH- sample (n=73) was 29 ± 13 years old and 51% were men. Crypts were related to the presence of sarcomere mutations (for ≥1 crypt, β=2.5; 95% confidence interval [CI], 0.5-4.4; P=0.014 and for ≥2 crypts, β=3.0; 95% CI, 0.8-7.9; P=0.004). In combination with 3 other parameters: anterior mitral valve leaflet elongation (β=2.1; 95% CI, 1.7-3.1; P<0.001), abnormal LV apical trabeculae (β=1.6; 95% CI, 0.8-2.5; P<0.001), and smaller LV end-systolic volumes (β=1.4; 95% CI, 0.5-2.3; P=0.001), multiple crypts indicated the presence of sarcomere gene mutations with 80% accuracy and an area under the curve of 0.85 (95% CI, 0.8-0.9). In this G+LVH- population, cardiac myosin-binding protein C mutation carriers had twice the prevalence of crypts when compared with the other combined mutations (47 versus 23%; odds ratio, 2.9; 95% CI, 1.1-7.9; P=0.045). CONCLUSIONS: The subclinical hypertrophic cardiomyopathy phenotype measured by cardiovascular magnetic resonance in a multicenter environment and consisting of crypts (particularly multiple), anterior mitral valve leaflet elongation, abnormal trabeculae, and smaller LV systolic cavity is indicative of the presence of sarcomere gene mutations and highlights the need for further study

A neurogenetic model for the study of schizophrenia spectrum disorders: The International 22q11.2 Deletion Syndrome Brain Behavior Consortium

Rare copy number variants contribute significantly to the risk for schizophrenia, with the 22q11.2 locus consistently implicated. Individuals with the 22q11.2 deletion syndrome (22q11DS) have an estimated 25-fold increased risk for schizophrenia spectrum disorders, compared to individuals in the general population. The International 22q11DS Brain Behavior Consortium is examining this highly informative neurogenetic syndrome phenotypically and genomically. Here we detail the procedures of the effort to characterize the neuropsychiatric and neurobehavioral phenotypes associated with 22q11DS, focusing on schizophrenia and subthreshold expression of psychosis. The genomic approach includes a combination of whole genome sequencing and genome-wide microarray technologies, allowing the investigation of all possible DNA variation and gene pathways influencing the schizophrenia-relevant phenotypic expression. A phenotypically rich data set provides a psychiatrically well-characterized sample of unprecedented size (n=1,616) that informs the neurobehavioral developmental course of 22q11DS. This combined set of phenotypic and genomic data will enable hypothesis testing to elucidate the mechanisms underlying the pathogenesis of schizophrenia spectrum disorders

A rare case of small bowel volvulus after jenjunoileal bariatric bypass requiring emergency surgery: a case report

<p>Abstract</p> <p>Introduction</p> <p>Bariatric surgery is on the increase throughout the world. Jejunoileal bypass bariatric procedures have fallen out of favor in western surgical centers due to the high rate of associated complications. They are, however, performed routinely in other centers and as a consequence of health tourism, management of complications related to these procedures may still be encountered.</p> <p>Case presentation</p> <p>We describe a rare case of small bowel obstruction in a 45-year-old British Caucasian woman, secondary to a volvulus of the jejunoileal anastomosis following bariatric bypass surgery. The pre-operative diagnosis was confirmed by radiology. We describe a successful surgical technique for this rare complication.</p> <p>Conclusions</p> <p>Bariatric surgery may be complicated by bowel obstruction. Early imaging is vital for diagnosis and effective management. The use of our surgical technique provides a simple and effective approach for the successful management of this bariatric complication.</p

Anatomy of the ankle ligaments: a pictorial essay

Understanding the anatomy of the ankle ligaments is important for correct diagnosis and treatment. Ankle ligament injury is the most frequent cause of acute ankle pain. Chronic ankle pain often finds its cause in laxity of one of the ankle ligaments. In this pictorial essay, the ligaments around the ankle are grouped, depending on their anatomic orientation, and each of the ankle ligaments is discussed in detail

Effects of Different Correlation Metrics and Preprocessing Factors on Small-World Brain Functional Networks: A Resting-State Functional MRI Study

Graph theoretical analysis of brain networks based on resting-state functional MRI (R-fMRI) has attracted a great deal of attention in recent years. These analyses often involve the selection of correlation metrics and specific preprocessing steps. However, the influence of these factors on the topological properties of functional brain networks has not been systematically examined. Here, we investigated the influences of correlation metric choice (Pearson's correlation versus partial correlation), global signal presence (regressed or not) and frequency band selection [slow-5 (0.01–0.027 Hz) versus slow-4 (0.027–0.073 Hz)] on the topological properties of both binary and weighted brain networks derived from them, and we employed test-retest (TRT) analyses for further guidance on how to choose the “best” network modeling strategy from the reliability perspective. Our results show significant differences in global network metrics associated with both correlation metrics and global signals. Analysis of nodal degree revealed differing hub distributions for brain networks derived from Pearson's correlation versus partial correlation. TRT analysis revealed that the reliability of both global and local topological properties are modulated by correlation metrics and the global signal, with the highest reliability observed for Pearson's-correlation-based brain networks without global signal removal (WOGR-PEAR). The nodal reliability exhibited a spatially heterogeneous distribution wherein regions in association and limbic/paralimbic cortices showed moderate TRT reliability in Pearson's-correlation-based brain networks. Moreover, we found that there were significant frequency-related differences in topological properties of WOGR-PEAR networks, and brain networks derived in the 0.027–0.073 Hz band exhibited greater reliability than those in the 0.01–0.027 Hz band. Taken together, our results provide direct evidence regarding the influences of correlation metrics and specific preprocessing choices on both the global and nodal topological properties of functional brain networks. This study also has important implications for how to choose reliable analytical schemes in brain network studies

Endophenotypes in a Dynamically Connected Brain

We examined the longitudinal genetic architecture of three parameters of functional brain connectivity. One parameter described overall connectivity (synchronization likelihood, SL). The two others were derived from graph theory and described local (clustering coefficient, CC) and global (average path length, L) aspects of connectivity. We measured resting state EEG in 1,438 subjects from four age groups of about 16, 18, 25 and 50 years. Developmental curves for SL and L indicate that connectivity is more random at adolescence and old age, and more structured in middle-aged adulthood. Individual variation in SL and L were moderately to highly heritable at each age (SL: 40–82%; L: 29–63%). Genetic factors underlying these phenotypes overlapped. CC was also heritable (25–49%) but showed no systematic overlap with SL and L. SL, CC, and L in the alpha band showed high phenotypic and genetic stability from 16 to 25 years. Heritability for parameters in the beta band was lower, and less stable across ages, but genetic stability was high. We conclude that the connectivity parameters SL, CC, and L in the alpha band show the hallmarks of a good endophenotype for behavior and developmental disorders

The distal fascicle of the anterior inferior tibiofibular ligament as a cause of tibiotalar impingement syndrome: a current concepts review

Impingement syndromes of the ankle involve either osseous or soft tissue impingement and can be anterior, anterolateral, or posterior. Ankle impingement syndromes are painful conditions caused by the friction of joint tissues, which are both the cause and the effect of altered joint biomechanics. The distal fascicle of the anterior inferior tibiofibular ligament (AITFL) is possible cause of anterior impingement. The objective of this article was to review the literature concerning the anatomy, pathogenesis, symptoms and treatment of the AITFL impingement and finally to formulate treatment recommendations. The AITFL starts from the distal tibia, 5 mm in average above the articular surface, and descends obliquely between the adjacent margins of the tibia and fibula, anterior to the syndesmosis to the anterior aspect of the lateral malleolus. The incidence of the accessory fascicle differs very widely in the several studies. The presence of the distal fascicle of the AITFL and also the contact with the anterolateral talus is probably a normal finding. It may become pathological, due to anatomical variations and/or anterolateral instability of the ankle resulting from an anterior talofibular ligament injury. When observed during an ankle arthroscopy, the surgeon should look for the criteria described to decide whether it is pathological and considering resection of the distal fascicle. The presence of the AITFL and the contact with the talus is a normal finding. An impingement of the AITFL can result from an anatomical variant or anteroposterior instability of the ankle. The diagnosis of ligamentous impingement in the anterior aspect of the ankle should be considered in patients who have chronic ankle pain in the anterolateral aspect of the ankle after an inversion injury and have a stable ankle, normal plain radiographs, and isolated point tenderness on the anterolateral aspect of the talar dome and in the anteroinferior tibiofibular ligament. The impingement syndrome can be treated arthroscopically

Secular trends: a ten-year comparison of the amount and type of physical activity and inactivity of random samples of adolescents in the Czech Republic

BACKGROUND: An optimal level of physical activity (PA) in adolescence influences the level of PA in adulthood. Although PA declines with age have been demonstrated repeatedly, few studies have been carried out on secular trends. The present study assessed levels, types and secular trends of PA and sedentary behaviour of a sample of adolescents in the Czech Republic. METHODS: The study comprised two cross-sectional cohorts of adolescents ten years apart. The analysis compared data collected through a week-long monitoring of adolescents' PA in 1998-2000 and 2008-2010. Adolescents wore either Yamax SW-701 or Omron HJ-105 pedometer continuously for 7 days (at least 10 hours per day) excluding sleeping, hygiene and bathing. They also recorded their number of steps per day, the type and duration of PA and sedentary behaviour (in minutes) on record sheets. In total, 902 adolescents (410 boys; 492 girls) aged 14-18 were eligible for analysis. RESULTS: Overweight and obesity in Czech adolescents participating in this study increased from 5.5% (older cohort, 1998-2000) to 10.4% (younger cohort, 2008-2010). There were no inter-cohort significant changes in the total amount of sedentary behaviour in boys. However in girls, on weekdays, there was a significant increase in the total duration of sedentary behaviour of the younger cohort (2008-2010) compared with the older one (1998-2000). Studying and screen time (television and computer) were among the main sedentary behaviours in Czech adolescents. The types of sedentary behaviour also changed: watching TV (1998-2000) was replaced by time spent on computers (2008-2010).The Czech health-related criterion (achieving 11,000 steps per day) decreased only in boys from 68% (1998-2000) to 55% (2008-2010). Across both genders, 55%-75% of Czech adolescents met the health-related criterion of recommended steps per day, however less participants in the younger cohort (2008-2010) met this criterion than in the older cohort (1998-2000) ten years ago. Adolescents' PA levels for the monitored periods of 1998-2000 and 2008-2010 suggest a secular decrease in the weekly number of steps achieved by adolescent boys and girls. CONCLUSION: In the younger cohort (2008-2010), every tenth adolescent was either overweight or obese; roughly twice the rate when compared to the older cohort (1998-2000). Sedentary behaviour seems relatively stable across the two cohorts as the increased time that the younger cohort (2008-2010) spent on computers is compensated with an equally decreased time spent watching TV or studying. Across both cohorts about half to three quarters of the adolescents met the health-related criterion for achieved number of steps. The findings show a secular decrease in PA amongst adolescents. The significant interaction effects (cohort × age; and cohort × gender) that this study found suggested that secular trends in PA differ by age and gender