Noninvasive spinal neuromodulation to map and augment lower urinary tract function in rhesus macaques

© 2019 Elsevier Inc. Dysfunction of the lower urinary tract (LUT) is prevalent in neurological disorders, including multiple sclerosis, stroke, spinal cord injury and neurodegenerative conditions. Common symptoms include urgency, incontinence, and urinary retention. Recent advances in neuromodulation have resulted in improved treatments for overactive bladder symptoms of urgency, frequency, and nocturia. However, there are presently no treatments available for the induction of voiding to overcome urinary retention. We demonstrate that transcutaneous spinal cord stimulation (TSCS), a non-invasive intervention, applied over the thoracolumbar spine in neurologically intact rhesus macaques can activate the LUT, including activation of the bladder detrusor muscle, the urethral sphincter and pelvic floor muscles. Urodynamic studies show improved voiding efficiency and decreased post-voiding residual volumes in the bladder, while maintaining coordinated activity in the detrusor and sphincter with physiologic detrusor peak pressure, contraction duration, and urine flow rate remaining unchanged. We conclude that TSCS may represent a novel approach to activate the LUT and enable voiding in select neurological conditions

Measuring Relations Between Concepts In Conceptual Spaces

The highly influential framework of conceptual spaces provides a geometric way of representing knowledge. Instances are represented by points in a high-dimensional space and concepts are represented by regions in this space. Our recent mathematical formalization of this framework is capable of representing correlations between different domains in a geometric way. In this paper, we extend our formalization by providing quantitative mathematical definitions for the notions of concept size, subsethood, implication, similarity, and betweenness. This considerably increases the representational power of our formalization by introducing measurable ways of describing relations between concepts.Comment: Accepted at SGAI 2017 (http://www.bcs-sgai.org/ai2017/). The final publication is available at Springer via https://doi.org/10.1007/978-3-319-71078-5_7. arXiv admin note: substantial text overlap with arXiv:1707.05165, arXiv:1706.0636

Squirrelpox virus: assessing prevalence, transmission and environmental degradation

Red squirrels (Sciurus vulgaris) declined in Great Britain and Ireland during the last century, due to habitat loss and the introduction of grey squirrels (Sciurus carolinensis), which competitively exclude the red squirrel and act as a reservoir for squirrelpox virus (SQPV). The disease is generally fatal to red squirrels and their ecological replacement by grey squirrels is up to 25 times faster where the virus is present. We aimed to determine: (1) the seropositivity and prevalence of SQPV DNA in the invasive and native species at a regional scale; (2) possible SQPV transmission routes; and, (3) virus degradation rates under differing environmental conditions. Grey (n = 208) and red (n = 40) squirrel blood and tissues were sampled. Enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qPCR) techniques established seropositivity and viral DNA presence, respectively. Overall 8% of squirrels sampled (both species combined) had evidence of SQPV DNA in their tissues and 22% were in possession of antibodies. SQPV prevalence in sampled red squirrels was 2.5%. Viral loads were typically low in grey squirrels by comparison to red squirrels. There was a trend for a greater number of positive samples in spring and summer than in winter. Possible transmission routes were identified through the presence of viral DNA in faeces (red squirrels only), urine and ectoparasites (both species). Virus degradation analyses suggested that, after 30 days of exposure to six combinations of environments, there were more intact virus particles in scabs kept in warm (25°C) and dry conditions than in cooler (5 and 15°C) or wet conditions. We conclude that SQPV is present at low prevalence in invasive grey squirrel populations with a lower prevalence in native red squirrels. Virus transmission could occur through urine especially during warm dry summer conditions but, more notably, via ectoparasites, which are shared by both species

Enhancing the African bioethics initiative

BACKGROUND: Medical ethics has existed since the time of Hippocrates. However, formal training in bioethics did not become established until a few decades ago. Bioethics has gained a strong foothold in health sciences in the developed world, especially in Europe and North America. The situation is quite different in many developing countries. In most African countries, bioethics – as established and practiced today in the west- is either non-existent or is rudimentary. DISCUSSION: Though bioethics has come of age in the developed and some developing countries, it is still largely "foreign" to most African countries. In some parts of Africa, some bioethics conferences have been held in the past decade to create research ethics awareness and ensure conformity to international guidelines for research with human participants. This idea has arisen in recognition of the genuine need to develop capacity for reviewing the ethics of research in Africa. It is also a condition required by external sponsors of collaborative research in Africa. The awareness and interest that these conferences have aroused need to be further strengthened and extended beyond research ethics to clinical practice. By and large, bioethics education in schools that train doctors and other health care providers is the hook that anchors both research ethics and clinical ethics. SUMMARY: This communication reviews the current situation of bioethics in Africa as it applies to research ethics workshops and proposes that in spite of the present efforts to integrate ethics into biomedical research in Africa, much still needs to be done to accomplish this. A more comprehensive approach to bioethics with an all-inclusive benefit is to incorporate formal ethics education into health training institutions in Africa

Periodic Accumulation of Regulatory T Cells in the Uterus: Preparation for the Implantation of a Semi-Allogeneic Fetus?

BACKGROUND: Naturally occurring Foxp3(+)regulatory T cells play an important role in the inhibition of an immunological attack of the fetus. As implantation of the fetus poses an immediate antigenic challenge, the immune system has to prepare itself for this event prior to implantation. METHODOLOGY AND PRINCIPAL FINDINGS: Here, we show using quantitative RT-PCR and flow cytometry that regulatory T cells accumulate in the uterus not only during pregnancy, but also every time the female becomes fertile. Their periodic accumulation is accompanied by matching fluctuations in uterine expression of several chemokines, which have been shown to play a role in the recruitment and retention of regulatory T cells. CONCLUSIONS/SIGNIFICANCE: The data lead us to propose that every time a female approaches estrus, regulatory T cells start to accumulate in the uterus in preparation for a possible implantation event. Once pregnancy is established, those regulatory T cells that have seen alloantigen need to be retained at their site of action. Whilst several chemokines appear to be involved in the recruitment and/or retention of regulatory T cells during estrus, in pregnancy this role appears to be taken over by CCL4

Internet-based medical education: a realist review of what works, for whom and in what circumstances

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Towards improving early diagnosis of congenital Chagas disease in an endemic setting.

: Congenital Trypanosoma cruzi transmission is now estimated to account for 22% of new infections, representing a significant public health problem across Latin America and internationally. Treatment during infancy is highly efficacious and well tolerated, but current assays for early detection fail to detect &gt;50% of infected neonates and 9 month follow-up is low. : Women presenting for delivery in two urban hospitals in Santa Cruz department, Bolivia were screened by rapid test. Specimens from infants of infected women were tested by microscopy (micromethod), quantitative PCR (qPCR) and IgM trypomastigote excreted-secreted antigen (TESA)-blots at birth and 1 month, and by IgG serology at 6 and 9 months. : Among 487 infants of 476 seropositive women, congenital T. cruzi infection was detected in 38 infants of 35 mothers (7.8%). In cord blood, qPCR, TESA-blot and micromethod sensitivities/specificities were 68.6%/99.1%, 58.3%/99.1% and 16.7%/100%, respectively. When birth and 1 month results were combined, cumulative sensitivities reached 84.2%, 73.7% and 34.2%, respectively. Low birth weight and/or respiratory distress were reported in 11 (29%) infected infants. Infants with clinical signs had higher parasite loads and were significantly more likely to be detected by micromethod. : The proportion of T. cruzi infected infants with clinical signs has fallen from the 1990s, but symptomatic congenital Chagas disease still represents a significant, albeit increasingly challenging to detect, public health problem. Molecular methods could facilitate earlier diagnosis and circumvent loss to follow-up but remain logistically and economically prohibitive for routine screening in resource-limited settings.<br/

Estresse e Burnout entre residentes multiprofissionais

OBJECTIVE: To identify associations between high-stress and burnout syndrome in multidisciplinary residents from a federal university in Rio Grande do Sul, Brazil. METHOD: This is an analytical, cross-sectional and quantitative study. A socio-demographic questionnaire, the Work Stress Scale and the Maslach Burnout Inventory-Health Services Survey (MBI-HSS) were applied to 37 residents between April and June 2011. P-valuesOBJETIVO: Identificar la asociación entre alto estrés y Burnout en residentes Multiprofesionales de una universidad federal de Rio Grande do Sul. MÉTODO: se trata de un estudio analítico, transversal, cuantitativo. Se aplicaron un formulario de datos socio-demográficos, la Escala de Estrés en el Trabajo y el Maslach Burnout Inventory- Health Services en 37 residentes entre Abril y Junio de 2011. Valores de pOBJETIVO: identificar a associação entre alto estresse e Burnout em residentes multiprofissionais de uma universidade federal do Rio Grande do Sul. MÉTODO: trata-se de estudo analítico, transversal, quantitativo. Aplicaram-se um formulário de dados socio demográficos, a Escala de Estresse no Trabalho e o Maslach Burnout Inventory-Human Services Survey (MBI-HSS) em 37 residentes entre abril e junho de 2011. Valores de

Cell-based analysis of CAD variants identifies individuals likely to benefit from uridine therapy.

PURPOSE: Pathogenic autosomal recessive variants in CAD, encoding the multienzymatic protein initiating pyrimidine de novo biosynthesis, cause a severe inborn metabolic disorder treatable with a dietary supplement of uridine. This condition is difficult to diagnose given the large size of CAD with over 1000 missense variants and the nonspecific clinical presentation. We aimed to develop a reliable and discerning assay to assess the pathogenicity of CAD variants and to select affected individuals that might benefit from uridine therapy. METHODS: Using CRISPR/Cas9, we generated a human CAD-knockout cell line that requires uridine supplements for survival. Transient transfection of the knockout cells with recombinant CAD restores growth in absence of uridine. This system determines missense variants that inactivate CAD and do not rescue the growth phenotype. RESULTS: We identified 25 individuals with biallelic variants in CAD and a phenotype consistent with a CAD deficit. We used the CAD-knockout complementation assay to test a total of 34 variants, identifying 16 as deleterious for CAD activity. Combination of these pathogenic variants confirmed 11 subjects with a CAD deficit, for whom we describe the clinical phenotype. CONCLUSIONS: We designed a cell-based assay to test the pathogenicity of CAD variants, identifying 11 CAD-deficient individuals who could benefit from uridine therapy