Finite element modeling and in vivo analysis of electrode configurations for selective stimulation of pudendal afferent fibers

<p>Abstract</p> <p>Background</p> <p>Intraurethral electrical stimulation (IES) of pudendal afferent nerve fibers can evoke both excitatory and inhibitory bladder reflexes in cats. These pudendovesical reflexes are a potential substrate for restoring bladder function in persons with spinal cord injury or other neurological disorders. However, the complex distribution of pudendal afferent fibers along the lower urinary tract presents a challenge when trying to determine the optimal geometry and position of IES electrodes for evoking these reflexes. This study aimed to determine the optimal intraurethral electrode configuration(s) and locations for selectively activating targeted pudendal afferents to aid future preclinical and clinical investigations.</p> <p>Methods</p> <p>A finite element model (FEM) of the male cat urethra and surrounding structures was generated to simulate IES with a variety of electrode configurations and locations. The activating functions (AFs) along pudendal afferent branches innervating the cat urethra were determined. Additionally, the thresholds for activation of pudendal afferent branches were measured in α-chloralose anesthetized cats.</p> <p>Results</p> <p>Maximum AFs evoked by intraurethral stimulation in the FEM and in vivo threshold intensities were dependent on stimulation location and electrode configuration.</p> <p>Conclusions</p> <p>A ring electrode configuration is ideal for IES. Stimulation near the urethral meatus or prostate can activate the pudendal afferent fibers at the lowest intensities, and allowed selective activation of the dorsal penile nerve or cranial sensory nerve, respectively. Electrode location was a more important factor than electrode configuration for determining stimulation threshold intensity and nerve selectivity.</p

Leukocyte-specific protein 1 regulates T-cell migration in rheumatoid arthritis

Copy number variations (CNVs) have been implicated in human diseases. However, it remains unclear how they affect immune dysfunction and autoimmune diseases, including rheumatoid arthritis (RA). Here, we identified a novel leukocyte-specific protein 1 (LSP1) deletion variant for RA susceptibility located in 11p15.5. We replicated that the copy number of LSP1 gene is significantly lower in patients with RA, which correlates positively with LSP1 protein expression levels. Differentially expressed genes in Lsp1-deficient primary T cells represent cell motility and immune and cytokine responses. Functional assays demonstrated that LSP1, induced by T-cell receptor activation, negatively regulates T-cell migration by reducing ERK activation in vitro. In mice with T-cell-dependent chronic inflammation, loss of Lsp1 promotes migration of T cells into the target tissues as well as draining lymph nodes, exacerbating disease severity. Moreover, patients with RA show diminished expression of LSP1 in peripheral T cells with increased migratory capacity, suggesting that the defect in LSP1 signaling lowers the threshold for T-cell activation. To our knowledge, our work is the first to demonstrate how CNVs result in immune dysfunction and a disease phenotype. Particularly, our data highlight the importance of LSP1 CNVs and LSP1 insufficiency in the pathogenesis of RA and provide previously unidentified insights into the mechanisms underlying T-cell migration toward the inflamed synovium in RA.1187Ysciescopu

Angiographic outcome of coronary artery bypass grafts: Radial Artery Database International Alliance

BACKGROUND: We used a large patient-level dataset including six angiographic randomized trials (RCTs) on coronary artery bypass conduits to explore incidence and determinants of coronary graft failure. METHODS: Patient-level angiographic data of six RCTs comparing long-term outcomes of the radial artery and other conduits were joined. Primary outcome was graft occlusion at maximum follow-up. The analysis was divided as follows: 1) left anterior descending coronary (LAD) distribution, 2) non-LAD distribution (circumflex and right coronary artery). To identify predictors of graft occlusion, mixed model multivariable Cox regression including all baseline characteristics with stratification by individual trials was used. RESULTS: 1091 patients and 2281 grafts were included (921 left internal mammary arteries, 74 right internal mammary arteries, 710 radial artery and 576 saphenous veins; all left internal mammary arteries were used on the LAD, the other conduits were used on the non-LAD distribution; mean angiographic follow up: 65±29 months). Occlusion rate was 2.3%, 13.5%, 9.4%, 17.5% for the left internal mammary arteries, right internal mammary arteries, radial artery and saphenous veins, respectively. At multivariable analysis type of conduit used, age, female gender, left ventricular ejection fraction<50% and use of the Y graft were significantly associated with graft occlusion in the non-LAD distribution. CONCLUSIONS: Our analyses showed that failure of the left internal mammary arteries to LAD bypass is a very uncommon event. For the non-LAD distribution, the non-use of radial artery, age, female gender, left ventricular ejection fraction<50% and use of the Y graft configuration were significantly associated with mid-term graft failure

Controlled epitaxial growth modes of ZnO nanostructures using different substrate crystal planes

A combined experimental and theoretical investigation has clarified the nanometre-scale vapour-phase epitaxial growth of ZnO nanostructures on different crystal planes of GaN substrates. Under typical growth conditions, ZnO nanorods grow perpendicular to the GaN(0001) plane, but thin flat films form on GaN(10 (1) over bar1), (10 (1) over bar0) and (1 (1) over bar 20). High-resolution X-ray diffraction data and transmission electron microscopy confirm the heteroepitaxial relationship between the ZnO nanostructures and GaN substrates. These results are consistent with first-principles theoretical calculations, indicating that the ZnO surface morphologies are mainly influenced by highly anisotropic GaN/ZnO interface energies. As a result of the large surface energy gradients, different ZnO nanostructures grow by preferential heteroepitaxial growth on different facets of regular GaN micropattern arrays. High-resolution transmission electron microscopy shows that ZnO nanotubes develop epitaxially on micropyramid tips, presumably as a result of enhanced nucleation and growth about the edges.open113031sciescopu

Ethylene supports colonization of plant roots by the mutualistic fungus Piriformospora indica

The mutualistic basidiomycete Piriformospora indica colonizes roots of mono- and dicotyledonous plants, and thereby improves plant health and yield. Given the capability of P. indica to colonize a broad range of hosts, it must be anticipated that the fungus has evolved efficient strategies to overcome plant immunity and to establish a proper environment for nutrient acquisition and reproduction. Global gene expression studies in barley identified various ethylene synthesis and signaling components that were differentially regulated in P. indica-colonized roots. Based on these findings we examined the impact of ethylene in the symbiotic association. The data presented here suggest that P. indica induces ethylene synthesis in barley and Arabidopsis roots during colonization. Moreover, impaired ethylene signaling resulted in reduced root colonization, Arabidopsis mutants exhibiting constitutive ethylene signaling, -synthesis or ethylene-related defense were hyper-susceptible to P. indica. Our data suggest that ethylene signaling is required for symbiotic root colonization by P. indica

Overexpression of sphingosine kinase 1 is associated with salivary gland carcinoma progression and might be a novel predictive marker for adjuvant therapy

<p>Abstract</p> <p>Background</p> <p>Overexpression of sphingosine kinase-1 (SPHK1) has been demonstrated to be associated with the development and progression in various types of human cancers. The current study was to characterize the expression of SPHK1 in salivary gland carcinomas (SGC) and to investigate the association between SPHK1 expression and progression of SGC.</p> <p>Methods</p> <p>The expression of SPHK1 was examined in 2 normal salivary gland tissues, 8 SGC tissues of various clinical stages, and 5 pairs of primary SGC and adjacent salivary gland tissues from the same patient, using real-time PCR and western blot analysis. Furthermore, the SPHK1 protein expression was analyzed in 159 clinicopathologically characterized SGC cases by immunohistochemistry. Statistical analyses were performed to determine the prognostic and diagnostic associations.</p> <p>Results</p> <p>SPHK1 expression was found to be markedly upregulated in SGC tissues than that in the normal salivary gland tissues and paired adjacent salivary gland tissues, at both mRNA and protein levels. Statistical analysis revealed a significant correlation of SPHK1 expression with the clinical stage (<it>P </it>= 0.005), T classification (<it>P </it>= 0.017), N classification (<it>P </it>= 0.009), M classification (<it>P </it>= 0.002), and pathological differentiation (<it>P </it>= 0.013). Patients with higher SPHK1 expression had shorter overall survival time, whereas patients with lower SPHK1 expression had better survival. Importantly, patients in the group without adjuvant therapy who exhibited high SPHK1 expression had significantly lower overall survival rates compared with those with low SPHK1 expression. Moreover, multivariate analysis suggested that SPHK1 expression might be an independent prognostic indicator for the survival of SGC patients.</p> <p>Conclusions</p> <p>Our results suggest that SPHK1 expression is associated with SGC progression, and might represent as a novel and valuable predictor for adjuvant therapy to SGC patients.</p

Voluntary exercise can strengthen the circadian system in aged mice

Consistent daily rhythms are important to healthy aging according to studies linking disrupted circadian rhythms with negative health impacts. We studied the effects of age and exercise on baseline circadian rhythms and on the circadian system's ability to respond to the perturbation induced by an 8 h advance of the light:dark (LD) cycle as a test of the system's robustness. Mice (male, mPer2luc/C57BL/6) were studied at one of two ages: 3.5 months (n = 39) and &gt;18 months (n = 72). We examined activity records of these mice under entrained and shifted conditions as well as mPER2::LUC measures ex vivo to assess circadian function in the suprachiasmatic nuclei (SCN) and important target organs. Age was associated with reduced running wheel use, fragmentation of activity, and slowed resetting in both behavioral and molecular measures. Furthermore, we observed that for aged mice, the presence of a running wheel altered the amplitude of the spontaneous firing rate rhythm in the SCN in vitro. Following a shift of the LD cycle, both young and aged mice showed a change in rhythmicity properties of the mPER2::LUC oscillation of the SCN in vitro, and aged mice exhibited longer lasting internal desynchrony. Access to a running wheel alleviated some age-related changes in the circadian system. In an additional experiment, we replicated the effect of the running wheel, comparing behavioral and in vitro results from aged mice housed with or without a running wheel (&gt;21 months, n = 8 per group, all examined 4 days after the shift). The impact of voluntary exercise on circadian rhythm properties in an aged animal is a novel finding and has implications for the health of older people living with environmentally induced circadian disruption

Tiny cystine stones in the gallbladder of a patient with cholecystolithiasis complicating acute cholecystitis: a case report

Cystine stones, the main component of which is cystine, are very common urinary calculi, but are rare in the gall bladder. In animals, there has been only one report of cystine gallstones in tree shrews, and to our knowledge, this is the first report of cystine gallstones in humans

Three little pieces for computer and relativity

Numerical relativity has made big strides over the last decade. A number of problems that have plagued the field for years have now been mostly solved. This progress has transformed numerical relativity into a powerful tool to explore fundamental problems in physics and astrophysics, and I present here three representative examples. These "three little pieces" reflect a personal choice and describe work that I am particularly familiar with. However, many more examples could be made.Comment: 42 pages, 11 figures. Plenary talk at "Relativity and Gravitation: 100 Years after Einstein in Prague", June 25 - 29, 2012, Prague, Czech Republic. To appear in the Proceedings (Edition Open Access). Collects results appeared in journal articles [72,73, 122-124