A pneumatic power harvesting ankle-foot orthosis to prevent foot-drop

<p>Abstract</p> <p>Background</p> <p>A self-contained, self-controlled, pneumatic power harvesting ankle-foot orthosis (PhAFO) to manage foot-drop was developed and tested. Foot-drop is due to a disruption of the motor control pathway and may occur in numerous pathologies such as stroke, spinal cord injury, multiple sclerosis, and cerebral palsy. The objectives for the prototype PhAFO are to provide toe clearance during swing, permit free ankle motion during stance, and harvest the needed power with an underfoot bellow pump pressurized during the stance phase of walking.</p> <p>Methods</p> <p>The PhAFO was constructed from a two-part (tibia and foot) carbon composite structure with an articulating ankle joint. Ankle motion control was accomplished through a cam-follower locking mechanism actuated via a pneumatic circuit connected to the bellow pump and embedded in the foam sole. Biomechanical performance of the prototype orthosis was assessed during multiple trials of treadmill walking of an able-bodied control subject (n = 1). Motion capture and pressure measurements were used to investigate the effect of the PhAFO on lower limb joint behavior and the capacity of the bellow pump to repeatedly generate the required pneumatic pressure for toe clearance.</p> <p>Results</p> <p>Toe clearance during swing was successfully achieved during all trials; average clearance 44 ± 5 mm. Free ankle motion was observed during stance and plantarflexion was blocked during swing. In addition, the bellow component repeatedly generated an average of 169 kPa per step of pressure during ten minutes of walking.</p> <p>Conclusion</p> <p>This study demonstrated that fluid power could be harvested with a pneumatic circuit built into an AFO, and used to operate an actuated cam-lock mechanism that controls ankle-foot motion at specific periods of the gait cycle.</p

Szeg\"o kernel asymptotics and Morse inequalities on CR manifolds

We consider an abstract compact orientable Cauchy-Riemann manifold endowed with a Cauchy-Riemann complex line bundle. We assume that the manifold satisfies condition Y(q) everywhere. In this paper we obtain a scaling upper-bound for the Szeg\"o kernel on (0, q)-forms with values in the high tensor powers of the line bundle. This gives after integration weak Morse inequalities, analogues of the holomorphic Morse inequalities of Demailly. By a refined spectral analysis we obtain also strong Morse inequalities which we apply to the embedding of some convex-concave manifolds.Comment: 40 pages, the constants in Theorems 1.1-1.8 have been modified by a multiplicative constant 1/2 ; v.2 is a final updat

Comprehensive linkage and linkage heterogeneity analysis of 4344 sibling pairs affected with hypertension from the Family Blood Pressure Program

Linkage analyses of complex, multifactorial traits and diseases, such as essential hypertension, have been difficult to interpret and reconcile. Many published studies provide evidence suggesting that different genes and genomic regions influence hypertension, but knowing which of these studies reflect true positive results is challenging. The reasons for this include the diversity of analytical methods used across these studies, the different samples and sample sizes in each study, and the complicated biological underpinnings of hypertension. We have undertaken a comprehensive linkage analysis of 371 autosomal microsatellite markers genotyped on 4,334 sibling pairs affected with hypertension from five ethnic groups sampled from 13 different field centers associated with the Family Blood Pressure Program (FBPP). We used a single analytical technique known to be robust to interpretive problems associated with a lack of completely informative markers to assess evidence for linkage to hypertension both within and across the ethnic groups and field centers. We find evidence for linkage to a number of genomic regions, with the most compelling evidence from analyses that combine data across field center and ethnic groups (e.g., chromosomes 2 and 9). We also pursued linkage analyses that accommodate locus heterogeneity, which is known to plague the identification of disease susceptibility loci in linkage studies of complex diseases. We find evidence for linkage heterogeneity on chromosomes 2 and 17. Ultimately our results suggest that evidence for linkage heterogeneity can only be detected with large sample sizes, such as the FBPP, which is consistent with theoretical sample size calculations. Genet. Epidemiol . 2007. © 2007 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56011/1/20202_ftp.pd

Retroperitoneal Castleman's tumor and paraneoplastic pemphigus: report of a case and review of the literature

BACKGROUND: Castleman's disease is a rare lymphoproliferative syndrome. Its etiology and pathogenesis are unclear. The disease can be occasionally associated with a paraneoplastic pemphigus (PNP), an autoimmune mucocutaneous disorder commonly seen in neoplasms of lymphocytic origin. CASE PRESENTATION: We present a case of a 63-year old male patient who was referred for surgical treatment of a lately diagnosed retroperitoneal pelvic mass. The patient had been already treated for two years due to progressive diffuse cutaneous lesions histologically consistent with lichen ruber verucosus and pemphigus vulgaris. Intraoperatively a highly vascularized solid mass occupying the small pelvis was resected after meticulous vascular ligation and hemostasis. After surgery and following immunosuppressive treatment a clear remission of the skin lesions was observed. CONCLUSION: Castleman's tumor should be always suspected when a retroperitoneal mass is combined with PNP. In a review of the literature we found 37 additional cases. Complete surgical resection of the tumor can be curative in most of the cases

Betel nut chewing and incidence of newly diagnosed type 2 diabetes mellitus in Taiwan.

<p>Abstract</p> <p>Background</p> <p>Betel nut chewing is associated with type 2 diabetes mellitus (T2DM) in a recent prevalence study in Taiwan. The present study further investigated its link with the incidence of newly diagnosed T2DM during the years 1992-1996.</p> <p>Methods</p> <p>Population-based datasets of a sample of 93,484 out of 256,036 diabetic patients from 66 medical settings using the National Health Insurance scheme covering > 96% of the population, published population prevalence of betel nut chewing and the governmental census of national population were used for calculation of odds ratios, incidence rates and incidence rate ratios between chewers and never-chewers in the male population for the year 1992 to 1996.</p> <p>Results</p> <p>Ever chewers among the diabetic patients were younger, more obese and had higher prevalence of parental diabetes than never-chewers (all <it>p </it>values < 0.001). Odds ratios for T2DM for ever chewers vs. never-chewers in the age of < 40, 40-49, 50-59, 60-69 and ≥70 years were 1.06 (0.92-1.23), 1.60 (1.45-1.76), 2.12 (1.88-2.39), 3.58 (3.10-4.13) and 7.14 (5.47-9.31), respectively. In 1996, incidence rates (per 100,000 population) in the respective age groups were 19.1, 251.5, 567.3, 721.7 and 971.4 for never-chewers; and were 30.2, 520.9, 2566.9, 11672.8 and 630.3 for ever chewers. The respective incidence rate ratios were 1.58, 2.07, 4.52, 16.17 and 0.65. The age-specific incidence rates and rate ratios were relatively consistent from 1992 to 1996. The differences in obesity and parental diabetes between ever chewers and never-chewers were mostly not statistically significant after age stratification, suggesting the link could not be attributed to these two factors.</p> <p>Conclusions</p> <p>Chewing betel nut is associated with newly diagnosed T2DM, supporting the suggestion that the habit is diabetogenic.</p

Toll-like receptor 2 gene polymorphisms, pulmonary tuberculosis, and natural killer cell counts

<p>Abstract</p> <p>Background</p> <p>To investigate whether the toll-like receptor 2 polymorphisms could influence susceptibility to pulmonary TB, its phenotypes, and blood lymphocyte subsets.</p> <p>Methods</p> <p>A total of 368 subjects, including 184 patients with pulmonary TB and 184 healthy controls, were examined for TLR2 polymorphisms over locus -100 (microsatellite guanine-thymine repeats), -16934 (T>A), -15607 (A>G), -196 to -174 (insertion>deletion), and 1350 (T>C). Eighty-six TB patients were examined to determine the peripheral blood lymphocyte subpopulations.</p> <p>Results</p> <p>We newly identified an association between the haplotype [A-G-(insertion)-T] and susceptibility to pulmonary TB (p = 0.006, false discovery rate q = 0.072). TB patients with systemic symptoms had a lower -196 to -174 deletion/deletion genotype frequency than those without systemic symptoms (5.7% vs. 17.7%; p = 0.01). TB patients with the deletion/deletion genotype had higher blood NK cell counts than those carrying the insertion allele (526 vs. 243.5 cells/μl, p = 0.009). TB patients with pleuritis had a higher 1350 CC genotype frequency than those without pleuritis (12.5% vs. 2.1%; p = 0.004). TB patients with the 1350 CC genotype had higher blood NK cell counts than those carrying the T allele (641 vs. 250 cells/μl, p = 0.004). TB patients carrying homozygous short alleles for GT repeats had higher blood NK cell counts than those carrying one or no short allele (641 vs. 250 cells/μl, p = 0.004).</p> <p>Conclusions</p> <p>TLR2 genetic polymorphisms influence susceptibility to pulmonary TB. TLR2 variants play a role in the development of TB phenotypes, probably by controlling the expansion of NK cells.</p

Tissue-specific gene expression templates for accurate molecular characterization of the normal physiological states of multiple human tissues with implication in development and cancer studies

<p>Abstract</p> <p>Background</p> <p>To elucidate the molecular complications in many complex diseases, we argue for the priority to construct a model representing the normal physiological state of a cell/tissue.</p> <p>Results</p> <p>By analyzing three independent microarray datasets on normal human tissues, we established a quantitative molecular model GET, which consists of 24 tissue-specific <it>G</it>ene <it>E</it>xpression <it>T</it>emplates constructed from a set of 56 genes, for predicting 24 distinct tissue types under disease-free condition. 99.2% correctness was reached when a large-scale validation was performed on 61 new datasets to test the tissue-prediction power of GET. Network analysis based on molecular interactions suggests a potential role of these 56 genes in tissue differentiation and carcinogenesis.</p> <p>Applying GET to transcriptomic datasets produced from tissue development studies the results correlated well with developmental stages. Cancerous tissues and cell lines yielded significantly lower correlation with GET than the normal tissues. GET distinguished melanoma from normal skin tissue or benign skin tumor with 96% sensitivity and 89% specificity.</p> <p>Conclusions</p> <p>These results strongly suggest that a normal tissue or cell may uphold its normal functioning and morphology by maintaining specific chemical stoichiometry among genes. The state of stoichiometry can be depicted by a compact set of representative genes such as the 56 genes obtained here. A significant deviation from normal stoichiometry may result in malfunction or abnormal growth of the cells.</p

H2B ubiquitylation is part of chromatin architecture that marks exon-intron structure in budding yeast

<p>Abstract</p> <p>Background</p> <p>The packaging of DNA into chromatin regulates transcription from initiation through 3' end processing. One aspect of transcription in which chromatin plays a poorly understood role is the co-transcriptional splicing of pre-mRNA.</p> <p>Results</p> <p>Here we provide evidence that H2B monoubiquitylation (H2BK123ub1) marks introns in <it>Saccharomyces cerevisiae</it>. A genome-wide map of H2BK123ub1 in this organism reveals that this modification is enriched in coding regions and that its levels peak at the transcribed regions of two characteristic subgroups of genes. First, long genes are more likely to have higher levels of H2BK123ub1, correlating with the postulated role of this modification in preventing cryptic transcription initiation in ORFs. Second, genes that are highly transcribed also have high levels of H2BK123ub1, including the ribosomal protein genes, which comprise the majority of intron-containing genes in yeast. H2BK123ub1 is also a feature of introns in the yeast genome, and the disruption of this modification alters the intragenic distribution of H3 trimethylation on lysine 36 (H3K36me3), which functionally correlates with alternative RNA splicing in humans. In addition, the deletion of genes encoding the U2 snRNP subunits, Lea1 or Msl1, in combination with an <it>htb-K123R </it>mutation, leads to synthetic lethality.</p> <p>Conclusion</p> <p>These data suggest that H2BK123ub1 facilitates cross talk between chromatin and pre-mRNA splicing by modulating the distribution of intronic and exonic histone modifications.</p

Foxp2 controls synaptic wiring of corticostriatal circuits and vocal communication by opposing Mef2c

Cortico-basal ganglia circuits are critical for speech and language and are implicated in autism spectrum disorder, in which language function can be severely affected. We demonstrate that in the mouse striatum, the gene Foxp2 negatively interacts with the synapse suppressor gene Mef2c. We present causal evidence that Mef2c inhibition by Foxp2 in neonatal mouse striatum controls synaptogenesis of corticostriatal inputs and vocalization in neonates. Mef2c suppresses corticostriatal synapse formation and striatal spinogenesis, but can itself be repressed by Foxp2 through direct DNA binding. Foxp2 deletion de-represses Mef2c, and both intrastriatal and global decrease of Mef2c rescue vocalization and striatal spinogenesis defects of Foxp2-deletion mutants. These findings suggest that Foxp2-Mef2C signaling is critical to corticostriatal circuit formation. If found in humans, such signaling defects could contribute to a range of neurologic and neuropsychiatric disorders.National Institutes of Health (U.S.) (Grant R37 HD028341)Eunice Kennedy Shriver National Institute of Child Health and Human Development (U.S.) (Award R37 HD028341