A 7-year follow-up of sacral anterior root stimulation for bladder control in patients with a spinal cord injury: quality of life and users' experiences\ud

Study design: Cross-sectional descriptive study.\ud \ud Objectives: To assess long-term effects and quality of life (QoL) of using sacral anterior root stimulation (SARS) in spinal cord injured patients.\ud \ud Setting: Neurosurgical and Urological Departments of a large teaching hospital and a large rehabilitation centre in the Netherlands.\ud \ud Methods: In all, 42 patients with complete spinal cord injury (SCI) implanted between 1987 and 2000 were included. A questionnaire was constructed to determine complications, technical failures and personal experiences of the patients. The Qualiveen questionnaire was used and the outcome was compared with data obtained from a reference group of 400 SCI patients with neurogenic bladder problems not using the bladder controller. The Qualiveen questionnaire measures disease-specific aspects in four domains with respect to limitations, constraints, fears and feelings and general QoL aspects, suitable for use in SCI patients with urinary disorders.\ud \ud Results: The results of 37 patients are presented. Our results with the bladder controller with respect to medical and technical complications and infection rates are similar to the results presented by others. From users' experiences, the most important advantages reported were a decreased infection rate (68%), improved social life (54%) and continence (54%). Comparison of the obtained results of our patient group with the Qualiveen questionnaire with a reference group not using the bladder controller indicates that the specific impact of urinary disorders in the four domains on QoL is reduced and that general QoL is improved.\ud \ud Conclusion: SARS is effective and safe for neurogenic bladder management in patients with complete SCI. Users' experiences are positive. Furthermore, this therapy seems to reduce the effects of urinary-disorder-specific QoL aspects, and to increase the QoL in general\u

Is it me? Self-recognition bias across sensory modalities and its relationship to autistic traits

Background Atypical self-processing is an emerging theme in autism research, suggested by lower self-reference effect in memory, and atypical neural responses to visual self-representations. Most research on physical self-processing in autism uses visual stimuli. However, the self is a multimodal construct, and therefore, it is essential to test self-recognition in other sensory modalities as well. Self-recognition in the auditory modality remains relatively unexplored and has not been tested in relation to autism and related traits. This study investigates self-recognition in auditory and visual domain in the general population and tests if it is associated with autistic traits. Methods Thirty-nine neurotypical adults participated in a two-part study. In the first session, individual participant’s voice was recorded and face was photographed and morphed respectively with voices and faces from unfamiliar identities. In the second session, participants performed a ‘self-identification’ task, classifying each morph as ‘self’ voice (or face) or an ‘other’ voice (or face). All participants also completed the Autism Spectrum Quotient (AQ). For each sensory modality, slope of the self-recognition curve was used as individual self-recognition metric. These two self-recognition metrics were tested for association between each other, and with autistic traits. Results Fifty percent ‘self’ response was reached for a higher percentage of self in the auditory domain compared to the visual domain (t = 3.142; P < 0.01). No significant correlation was noted between self-recognition bias across sensory modalities (τ = −0.165, P = 0.204). Higher recognition bias for self-voice was observed in individuals higher in autistic traits (τ AQ = 0.301, P = 0.008). No such correlation was observed between recognition bias for self-face and autistic traits (τ AQ = −0.020, P = 0.438). Conclusions Our data shows that recognition bias for physical self-representation is not related across sensory modalities. Further, individuals with higher autistic traits were better able to discriminate self from other voices, but this relation was not observed with self-face. A narrow self-other overlap in the auditory domain seen in individuals with high autistic traits could arise due to enhanced perceptual processing of auditory stimuli often observed in individuals with autism

SMAR1 binds to T(C/G) repeatvand inhibits tumor progression by regulating miR-371-373 cluster

Chromatin architecture and dynamics are regulated by various histone and non-histone proteins. The matrix attachment region binding proteins (MARBPs) play a central role in chromatin organization and function through numerous regulatory proteins. In the present study, we demonstrate that nuclear matrix protein SMAR1 orchestrates global gene regulation as determined by massively parallel ChIPsequencing. The study revealed that SMAR1 binds to T(C/G) repeat and targets genes involved in diverse biological pathways. We observe that SMAR1 binds and targets distinctly different genes based on the availability of p53. Our data suggest that SMAR1 binds and regulates one of the imperative microRNA clusters in cancer and metastasis, miR-371-373. It negatively regulates miR-371-373 transcription as confirmed by SMAR1 overexpression and knockdown studies. Further, deletion studies indicate that a ~200 bp region in the miR-371-373 promoter is necessary for SMAR1 binding and transcriptional repression. Recruitment of HDAC1/mSin3A complex by SMAR1, concomitant with alteration of histone marks results in downregulation of the miRNA cluster. The regulation of miR-371-373 by SMAR1 inhibits breast cancer tumorigenesis and metastasis as determined by in vivo experiments. Overall, our study highlights the binding of SMAR1 to T(C/G) repeat and its role in cancer through miR-371-37

Intraoperative Graft Flow Profiles in Coronary Artery Bypass Surgery: a Meta-Analysis

Background: Conduits used in coronary artery bypass artery grafting (CABG) have different properties and flow profiles. We compared intraoperative mean graft flow (MGF) between arterial and venous conduits, off-pump CABG (OPCABG) and on-pump CABG (ONCABG) procedures, skeletonized and pedicled internal mammary artery (IMA) grafts, and pulsatility index (PI) between OPCABG and ONCABG, in pairwise meta-analyses. Methods: Following a systematic literature search, all studies comparing MGF in arterial and venous grafts, were included. The primary endpoint was comparison of pooled MGF between arterial and venous grafts. Secondary endpoints were comparisons of pooled MGF in OPCABG vs ONCABG, anastomosed skeletonized vs pedicled IMA grafts, free skeletonized vs pedicled IMA grafts and PI in OPCABG versus ONCABG. Results: A total of 25 studies with 4443 patients were included. Compared with venous grafts, arterial grafts had lower MGF (standardized mean difference [SMD], -0.28; 95% confidence interval [CI, -0.34; -0.22]; P < .001). OPCABG was associated with significantly lower MGF compared to ONCABG (SMD, -0.29; 95%CI, -0.50; -0.08]; P = .01). No differences were found in MGF between skeletonized vs pedicled IMA after anastomosis (SMD, 0.32; 95%CI [-0.08; 0.71]; P = .11) or in free flow (SMD, 0.76; 95%CI [-0.14; 1.65]; P = .10). No difference was found in PI between OPCABG and ONCABG. At meta-regression, age was associated with higher MGF, while OPCABG was associated with lower MGF. Conclusions: Intraoperative flow of venous conduits is higher than that of arterial grafts. Compared to OPCABG surgery, graft flow is higher in ONCABG. In skeletonized and pedicled IMA conduits, no difference in flow profiles was found.info:eu-repo/semantics/publishedVersio

A resting state network in the motor control circuit of the basal ganglia

<p>Abstract</p> <p>Background</p> <p>In the absence of overt stimuli, the brain shows correlated fluctuations in functionally related brain regions. Approximately ten largely independent resting state networks (RSNs) showing this behaviour have been documented to date. Recent studies have reported the existence of an RSN in the basal ganglia - albeit inconsistently and without the means to interpret its function. Using two large study groups with different resting state conditions and MR protocols, the reproducibility of the network across subjects, behavioural conditions and acquisition parameters is assessed. Independent Component Analysis (ICA), combined with novel analyses of temporal features, is applied to establish the basis of signal fluctuations in the network and its relation to other RSNs. Reference to prior probabilistic diffusion tractography work is used to identify the basal ganglia circuit to which these fluctuations correspond.</p> <p>Results</p> <p>An RSN is identified in the basal ganglia and thalamus, comprising the pallidum, putamen, subthalamic nucleus and substantia nigra, with a projection also to the supplementary motor area. Participating nuclei and thalamo-cortical connection probabilities allow this network to be identified as the motor control circuit of the basal ganglia. The network was reproducibly identified across subjects, behavioural conditions (fixation, eyes closed), field strength and echo-planar imaging parameters. It shows a frequency peak at 0.025 ± 0.007 Hz and is most similar in spectral composition to the Default Mode (DM), a network of regions that is more active at rest than during task processing. Frequency features allow the network to be classified as an RSN rather than a physiological artefact. Fluctuations in this RSN are correlated with those in the task-positive fronto-parietal network and anticorrelated with those in the DM, whose hemodynamic response it anticipates.</p> <p>Conclusion</p> <p>Although the basal ganglia RSN has not been reported in most ICA-based studies using a similar methodology, we demonstrate that it is reproducible across subjects, common resting state conditions and imaging parameters, and show that it corresponds with the motor control circuit. This characterisation of the basal ganglia network opens a potential means to investigate the motor-related neuropathologies in which the basal ganglia are involved.</p

Development of Second-Generation VEGFR Tyrosine Kinase Inhibitors: Current Status

The vascular endothelial growth factor (VEGF) signaling pathway appears to be the dominant pathway involved in tumor angiogenesis, providing a rationale for targeting the VEGF receptors (VEGFR-1, -2, and -3) in the treatment of cancers. In particular, VEGF signaling is thought to be important in renal cell carcinoma (RCC) because of the deregulation of the pathway through nearly uniform loss of the von Hippel Lindau protein. The tyrosine kinase inhibitors (TKIs) sorafenib, sunitinib, and pazopanib are approved by the US Food and Drug Administration for the treatment of advanced RCC; however, these multitargeted agents inhibit a wide range of kinase targets in addition to the VEGFRs, resulting in a range of adverse effects unrelated to efficient VEGF blockade. This article reviews recent advances in the development of the second-generation VEGFR TKIs, including the more selective VEGFR TKIs tivozanib and axitinib, and focuses on the potential benefits of novel inhibitors with improved potency and selectivity

Human Immunodeficiency Virus-1 Uses the Mannose-6-Phosphate Receptor to Cross the Blood-Brain Barrier

HIV-1 circulates both as free virus and within immune cells, with the level of free virus being predictive of clinical course. Both forms of HIV-1 cross the blood-brain barrier (BBB) and much progress has been made in understanding the mechanisms by which infected immune cells cross the blood-brain barrier BBB. How HIV-1 as free virus crosses the BBB is less clear as brain endothelial cells are CD4 and galactosylceramide negative. Here, we found that HIV-1 can use the mannose-6 phosphate receptor (M6PR) to cross the BBB. Brain perfusion studies showed that HIV-1 crossed the BBB of all brain regions consistent with the uniform distribution of M6PR. Ultrastructural studies showed HIV-1 crossed by a transcytotic pathway consistent with transport by M6PR. An in vitro model of the BBB was used to show that transport of HIV-1 was inhibited by mannose, mannan, and mannose-6 phosphate and that enzymatic removal of high mannose oligosaccharide residues from HIV-1 reduced transport. Wheatgerm agglutinin and protamine sulfate, substances known to greatly increase transcytosis of HIV-1 across the BBB in vivo, were shown to be active in the in vitro model and to act through a mannose-dependent mechanism. Transport was also cAMP and calcium-dependent, the latter suggesting that the cation-dependent member of the M6PR family mediates HIV-1 transport across the BBB. We conclude that M6PR is an important receptor used by HIV-1 to cross the BBB

Spatial Distribution and Risk Factors of Highly Pathogenic Avian Influenza (HPAI) H5N1 in China

Highly pathogenic avian influenza (HPAI) H5N1 was first encountered in 1996 in Guangdong province (China) and started spreading throughout Asia and the western Palearctic in 2004–2006. Compared to several other countries where the HPAI H5N1 distribution has been studied in some detail, little is known about the environmental correlates of the HPAI H5N1 distribution in China. HPAI H5N1 clinical disease outbreaks, and HPAI virus (HPAIV) H5N1 isolated from active risk-based surveillance sampling of domestic poultry (referred to as HPAIV H5N1 surveillance positives in this manuscript) were modeled separately using seven risk variables: chicken, domestic waterfowl population density, proportion of land covered by rice or surface water, cropping intensity, elevation, and human population density. We used bootstrapped logistic regression and boosted regression trees (BRT) with cross-validation to identify the weight of each variable, to assess the predictive power of the models, and to map the distribution of HPAI H5N1 risk. HPAI H5N1 clinical disease outbreak occurrence in domestic poultry was mainly associated with chicken density, human population density, and elevation. In contrast, HPAIV H5N1 infection identified by risk-based surveillance was associated with domestic waterfowl density, human population density, and the proportion of land covered by surface water. Both models had a high explanatory power (mean AUC ranging from 0.864 to 0.967). The map of HPAIV H5N1 risk distribution based on active surveillance data emphasized areas south of the Yangtze River, while the distribution of reported outbreak risk extended further North, where the density of poultry and humans is higher. We quantified the statistical association between HPAI H5N1 outbreak, HPAIV distribution and post-vaccination levels of seropositivity (percentage of effective post-vaccination seroconversion in vaccinated birds) and found that provinces with either outbreaks or HPAIV H5N1 surveillance positives in 2007–2009 appeared to have had lower antibody response to vaccination. The distribution of HPAI H5N1 risk in China appears more limited geographically than previously assessed, offering prospects for better targeted surveillance and control interventions

Different Gain/Loss Sensitivity and Social Adaptation Ability in Gifted Adolescents during a Public Goods Game

Gifted adolescents are considered to have high IQs with advanced mathematical and logical performances, but are often thought to suffer from social isolation or emotional mal-adaptation to the social group. The underlying mechanisms that cause stereotypic portrayals of gifted adolescents are not well known. We aimed to investigate behavioral performance of gifted adolescents during social decision-making tasks to assess their affective and social/non-social cognitive abilities. We examined cooperation behaviors of 22 gifted and 26 average adolescents during an iterative binary public goods (PG) game, a multi-player social interaction game, and analyzed strategic decision processes that include cooperation and free-riding. We found that the gifted adolescents were more cooperative than average adolescents. Particularly, comparing the strategies for the PG game between the two groups, gifted adolescents were less sensitive to loss, yet were more sensitive to gain. Additionally, the behavioral characteristics of average adolescents, such as low trust of the group and herding behavior, were not found in gifted adolescents. These results imply that gifted adolescents have a high cognitive ability but a low ability to process affective information or to adapt in social groups compared with average adolescents. We conclude that gain/loss sensitivity and the ability to adapt in social groups develop to different degrees in average and gifted adolescents

Habitat Composition and Connectivity Predicts Bat Presence and Activity at Foraging Sites in a Large UK Conurbation

Background: Urbanization is characterized by high levels of sealed land-cover, and small, geometrically complex, fragmented land-use patches. The extent and density of urbanized land-use is increasing, with implications for habitat quality, connectivity and city ecology. Little is known about densification thresholds for urban ecosystem function, and the response of mammals, nocturnal and cryptic taxa are poorly studied in this respect. Bats (Chiroptera) are sensitive to changing urban form at a species, guild and community level, so are ideal model organisms for analyses of this nature. Methodology/Principal Findings: We surveyed bats around urban ponds in the West Midlands conurbation, United Kingdom (UK). Sites were stratified between five urban land classes, representing a gradient of built land-cover at the 1 km 2 scale. Models for bat presence and activity were developed using land-cover and land-use data from multiple radii around each pond. Structural connectivity of tree networks was used as an indicator of the functional connectivity between habitats. All species were sensitive to measures of urban density. Some were also sensitive to landscape composition and structural connectivity at different spatial scales. These results represent new findings for an urban area. The activity of Pipistrellus pipistrellus (Schreber 1774) exhibited a non-linear relationship with the area of built land-cover, being much reduced beyond the threshold of,60 % built surface. The presence of tree networks appears to mitigate the negative effects of urbanization for this species