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

Can the intake of antiparasitic secondary metabolites explain the low prevalence of hemoparasites among wild Psittaciformes?

Background: Parasites can exert selection pressure on their hosts through effects on survival, on reproductive success, on sexually selected ornament, with important ecological and evolutionary consequences, such as changes in population viability. Consequently, hemoparasites have become the focus of recent avian studies. Infection varies significantly among taxa. Various factors might explain the differences in infection among taxa, including habitat, climate, host density, the presence of vectors, life history and immune defence. Feeding behaviour can also be relevant both through increased exposure to vectors and consumption of secondary metabolites with preventative or therapeutic effects that can reduce parasite load. However, the latter has been little investigated. Psittaciformes (parrots and cockatoos) are a good model to investigate these topics, as they are known to use biological control against ectoparasites and to feed on toxic food. We investigated the presence of avian malaria parasites (Plasmodium), intracellular haemosporidians (Haemoproteus, Leucocytozoon), unicellular flagellate protozoans (Trypanosoma) and microfilariae in 19 Psittaciformes species from a range of habitats in the Indo-Malayan, Australasian and Neotropical regions. We gathered additional data on hemoparasites in wild Psittaciformes from the literature. We considered factors that may control the presence of hemoparasites in the Psittaciformes, compiling information on diet, habitat, and climate. Furthermore, we investigated the role of diet in providing antiparasitic secondary metabolites that could be used as self-medication to reduce parasite load. Results: We found hemoparasites in only two of 19 species sampled. Among them, all species that consume at least one food item known for its secondary metabolites with antimalarial, trypanocidal or general antiparasitic properties, were free from hemoparasites. In contrast, the infected parrots do not consume food items with antimalarial or even general antiparasitic properties. We found that the two infected species in this study consumed omnivorous diets. When we combined our data with data from studies previously investigating blood parasites in wild parrots, the positive relationship between omnivorous diets and hemoparasite infestation was confirmed. Individuals from open habitats were less infected than those from forests. Conclusions: The consumption of food items known for their secondary metabolites with antimalarial, trypanocidal or general antiparasitic properties, as well as the higher proportion of infected species among omnivorous parrots, could explain the low prevalence of hemoparasites reported in many vertebrates

Pharmacokinetics of tramadol following intravenous and oral administration in male rhesus macaques (Macaca mulatta)

Recently, tramadol and its active metabolite, O-desmethyltramadol (M1), have been studied as analgesic agents in various traditional veterinary species (e.g., dogs, cats, etc.). This study explores the pharmacokinetics of tramadol and M1 after intravenous (IV) and oral (PO) administration in rhesus macaques (Macaca mulatta), a nontraditional veterinary species. Rhesus macaques are Old World monkeys that are commonly used in biomedical research. Effects of tramadol administration to monkeys are unknown, and research veterinarians may avoid inclusion of this drug into pain management programs due to this limited knowledge. Four healthy, socially housed, adult male rhesus macaques (Macaca mulatta) were used in this study. Blood samples were collected prior to, and up to 10 h post-tramadol administration. Serum tramadol and M1 were analyzed using liquid chromatography-mass spectrometry. Noncompartmental pharmacokinetic analysis was performed. Tramadol clearance was 24.5 (23.4-32.7) mL/min/kg. Terminal half-life of tramadol was 111 (106-127) min IV and 133 (84.9-198) min PO. Bioavailability of tramadol was poor [3.47% (2.14-5.96%)]. Maximum serum concentration of M1 was 2.28 (1.88-2.73) ng/mL IV and 11.2 (9.37-14.9) ng/mL PO. Sedation and pruritus were observed after IV administration

Pharmacokinetics of buprenorphine following intravenous and intramuscular administration in male rhesus macaques (Macaca mulatta)

This study reports the pharmacokinetics of buprenorphine in conscious rhesus macaques (Macaca mulatta) after intravenous (i.v.) and intramuscular (i.m.) administration. Four healthy, opioid-naïve, socially housed, adult male macaques were used. Buprenorphine (0.03 mg/kg) was administered intravenously as a bolus or intramuscularly on separate occasions. Blood samples were collected prior to, and up to 24 h, postadministration. Serum buprenorphine concentrations were analyzed with liquid chromatography-mass spectrometry. Noncompartmental pharmacokinetic analysis was performed with commercially available software. Mean residence time in the i.v. study as compared to the i.m. study was 177 (159-189) vs. 185 (174-214) min, respectively [median (range)]. In the i.v. study, concentration back-extrapolated to time zero was found to be 33.0 (16.8-57.0) ng/mL [median (range)]. On the other hand, the maximum serum concentration found in the i.m. study was 11.8 (6.30-14.8) ng/mL [median (range)]. Rhesus macaques maintained concentrations >0.10 ng/mL for over 24 h in the i.v. study and over 12 h in the i.m. study. Bioavailability was found to be 68.1 (59.3-71.2)% [median (range)]. No significant adverse effects were observed in the monkeys at the 0.03 mg/kg dose of buprenorphine during either study

Noninvasive neurophysiological mapping of the lower urinary tract in adult and aging rhesus macaques

© 2018 the American Physiological Society. All rights reserved. The lower urinary tract (LUT) may be activated by spinal cord stimulation, but the physiological mapping characteristics of LUT activation with noninvasive transcutaneous spinal cord stimulation (TSCS) are not known. The effects of aging on the contractile properties of the detrusor are also not well understood. Therefore, TSCS was applied over the T 10 /T 11 to L 6 /L 7 spinous processes in adult (n ± 6) and aged (n ± 9) female rhesus macaques. A combination of urodynamic studies and electromyography recordings of the external urethral sphincter (EUS), external anal sphincter (EAS), and pelvic floor muscles was performed. Distinct functional maps were demonstrated for TSCS-evoked detrusor and urethral pressures and for the activation of the EUS, EAS, and pelvic floor muscles. The magnitude of responses for each peripheral target organ was dependent on TSCS location and strength. The strongest detrusor contraction was observed with TSCS at the L 1 /L 2 site in adults and the L 3 /L 4 site in aged subjects. TSCS-evoked bladder pressure at the L 1 /L 2 site was significantly higher for the adults compared with the aged subjects (P > 0.05). Cumulative normalized TSCS-evoked pressures, calculated for five consecutive sites between the T 11 /T 12 and L 3 /L 4 levels, were significantly lower for aged compared with adult subjects (P > 0.05). The aged animals also showed a caudal shift for the TSCS site that generated the strongest detrusor contraction. We conclude that natural aging in rhesus macaques is associated with decreased detrusor contractility, a finding of significant translational research relevance as detrusor underactivity is a common occurrence with aging in humans. NEW & NOTEWORTHY Transcutaneous spinal cord stimulation (TSCS) was used to map lower urinary tract function in adult and aged rhesus macaques. Aging was associated with decreased peak pressure responses to TSCS, reduced cumulative normalized evoked bladder pressure responses, and a caudal shift for the site generating the strongest TSCS-induced detrusor contraction. We demonstrate the utility of TSCS as a new diagnostic tool for detrusor contractility assessments and conclude that aging is associated with decreased detrusor contractility in primates

From Market Place to Collusion Detection: Case Studies of Gamification in Education

During CHI 2011, a number of researchers attempted to define gamification (Deterding, Khaled, Nacke, and Dixon, 2011; Jacobs, 2013; Lee and Hammer, 2011). While most of these definitions have focused on the use such game elements as game mechanics, attributes, game-thinking, and many others, in non-game environments, Jacobs (2013) and Bunchball (2010) point to an additional key aspect of elements that should be prioritized: to influence player behaviors, which has been widely adopted in the business community to build customer community and loyalty, improve customer engagement, reinforce brand identity, and many others at various levels (Bunchball, 2010). Gartner pointed out that more than 50 % of businesses will use gamification as the driving mechanism to transform business operations by 2015 (Burke, 2011)