Quantification of anandamide and 2-arachidonoylglycerol plasma levels to examine potential influences of tetrahydrocannabinol application on the endocannabinoid system in humans

The effects of tetrahydrocannabinol (THC) and endogenous cannabinoids (endocannabinoids, ECs) are both mediated by activation of the cannabinoid receptors CB1 and CB2. Exogenous activation of these receptors by THC could therefore alter EC levels. We tested this hypothesis in healthy volunteers (n = 25) who received a large intravenous dose of THC (0.10 mg/kg). Effects on the EC system were quantified by serial measurements of plasma ECs after THC administration. Eleven blood samples were drawn during the first 5 h after THC administration and two more samples after 24 and 48 h. THC, its metabolites THC-OH (biologically active) and THC-COOH (non-active), and the ECs anandamide and 2-arachidonoylglycerol (2-AG) were quantified by liquid chromatography-mass spectrometry. EC-plasma levels showed a biphasic response after THC injection reaching maximal values at 30 min. Anandamide increased slightly from 0.58 ± 0.21 ng/ml at baseline to 0.64 ± 0.24 ng/ml (p < 0.05) and 2-AG from 7.60 ± 4.30 ng/ml to 9.50 ± 5.90 ng/ml (p < 0.05). After reaching maximal concentrations, EC plasma levels decreased markedly to a nadir of 300 min after THC administration (to 0.32 ± 0.15 ng/ml for anandamide and to 5.50 ± 3.01 ng/ml for 2-AG, p < 0.05). EC plasma concentrations returned to near baseline levels until 48 h after the experiment. THC (0.76 ± 0.16 ng/ml) and THC-OH (0.36 ± 0.17 ng/ml) were still measurable at 24 h and remained detectible until 48 h after THC administration. Although the underlying mechanism is not clear, high doses of intravenous THC appear to influence endogenous cannabinoid concentrations and presumably EC-signalling.

Differentiation between Staphylococcus aureus and coagulase-negative Staphylococcus species by real-time PCR including detection of methicillin resistants in comparison to conventional microbiology testing.

BACKGROUND Staphylococcus aureus has long been recognized as a major pathogen. Methicillin-resistant strains of S. aureus (MRSA) and methicillin-resistant strains of S. epidermidis (MRSE) are among the most prevalent multiresistant pathogens worldwide, frequently causing nosocomial and community-acquired infections. METHODS In the present pilot study, we tested a polymerase chain reaction (PCR) method to quickly differentiate Staphylococci and identify the mecA gene in a clinical setting. RESULTS Compared to the conventional microbiology testing the real-time PCR assay had a higher detection rate for both S. aureus and coagulase-negative Staphylococci (CoNS; 55 vs. 32 for S. aureus and 63 vs. 24 for CoNS). Hands-on time preparing DNA, carrying out the PCR, and evaluating results was less than 5 h. CONCLUSIONS The assay is largely automated, easy to adapt, and has been shown to be rapid and reliable. Fast detection and differentiation of S. aureus, CoNS, and the mecA gene by means of this real-time PCR protocol may help expedite therapeutic decision-making and enable earlier adequate antibiotic treatment.

Bond Strength of Resin Composite to Dentin with Different Adhesive Systems: Influence of Relative Humidity and Application Time.

PURPOSE To investigate the influence of relative humidity and application time on bond strength to dentin of different classes of adhesive systems. MATERIALS AND METHODS A total of 360 extracted human molars were ground to mid-coronal dentin. The dentin specimens were treated with one of six adhesive systems (Syntac Classic, OptiBond FL, Clearfil SE Bond, AdheSE, Xeno Select, or Scotchbond Universal), and resin composite (Filtek Z250) was applied to the treated dentin surface under four experimental conditions (45% relative humidity/application time according to manufacturers' instructions; 45% relative humidity/reduced application time; 85% relative humidity/application time according to manufacturers' instructions; 85% relative humidity/reduced application time). After storage (37°C, 100% humidity, 24 h), shear bond strength (SBS) was measured and data analyzed with nonparametric ANOVA followed by Kruskal-Wallis tests and Mann-Whitney U-tests with Bonferroni-Holm correction for multiple testing (level of significance: α = 0.05). RESULTS Increased relative humidity and reduced application time had no effect on SBS for Clearfil SE Bond and Scotchbond Universal (p = 1.00). For Syntac Classic, OptiBond FL, AdheSE, and Xeno Select there was no effect on SBS of reduced application time of the adhesive system (p ≥ 0.403). However, increased relative humidity significantly reduced SBS for Syntac Classic, OptiBond FL, and Xeno Select irrespective of application time (p ≤ 0.003), whereas for AdheSE, increased relative humidity significantly reduced SBS at recommended application time only (p = 0.002). CONCLUSION Generally, increased relative humidity had a detrimental effect on SBS to dentin, but reduced application time had no effect.

Clinical Practice Recommendations on Genetic Testing of CYP2C9 and VKORC1 Variants in Warfarin Therapy

OBJECTIVE To systematically review evidence on genetic variants influencing outcomes during warfarin therapy and provide practice recommendations addressing the key questions: (1) Should genetic testing be performed in patients with an indication for warfarin therapy to improve achievement of stable anticoagulation and reduce adverse effects? (2) Are there subgroups of patients who may benefit more from genetic testing compared with others? (3) How should patients with an indication for warfarin therapy be managed based on their genetic test results? METHODS A systematic literature search was performed for VKORC1 and CYP2C9 and their association with warfarin therapy. Evidence was critically appraised, and clinical practice recommendations were developed based on expert group consensus. RESULTS Testing of VKORC1 (-1639G>A), CYP2C9*2, and CYP2C9*3 should be considered for all patients, including pediatric patients, within the first 2 weeks of therapy or after a bleeding event. Testing for CYP2C9*5, *6, *8, or *11 and CYP4F2 (V433M) is currently not recommended. Testing should also be considered for all patients who are at increased risk of bleeding complications, who consistently show out-of-range international normalized ratios, or suffer adverse events while receiving warfarin. Genotyping results should be interpreted using a pharmacogenetic dosing algorithm to estimate the required dose. SIGNIFICANCE This review provides the latest update on genetic markers for warfarin therapy, clinical practice recommendations as a basis for informed decision making regarding the use of genotype-guided dosing in patients with an indication for warfarin therapy, and identifies knowledge gaps to guide future research.

Rapid and accurate G M1-gangliosidosis diagnosis using a parentage testing microsatellite

The G M1-gangliosidosis is an autosomal recessive lysosomal storage disease caused by structural defects of the beta-galactosidase gene (GLB1) which lead to a severe phenotypical impairment in homozygous individuals, whereas heterozygous carriers remain clinically normal. Currently employed DNA parentage tests include the analysis of microsatellites, which also have a diagnostic predictive value. The aim of this study was to provide a reliable tool for genotyping the canine GLB1 which can be effectively integrated in parentage testing investigations. For this purpose the association between the GLB1 gene and the AHT K253 microsatellite was analyzed in 30 Alaskan huskies (11 GLB1+/+, 17 GLB1+/- and 2 GLB1-/- dogs). The 143 bp AHT K253 microsatellite allele was identified only in GLB1+/- and GLB1-/- animals and was in strong linkage disequilibrium with the causative mutation for G M1-gangliosidosis, a 19 bp duplication within exon 15 of the GLB1 gene. The results of the present study revealed a 100% concordance between the previous established genotypes and those obtained after the analysis of the AHT K253 microsatellite. Thus, the genotype of the AHT K253 microsatellite, which is routinely determined during dog parentage testing, has a high predictive value for the G M1-gangliosidosis carrier status.

HIV testing and burden of HIV infection in black cancer patients in Johannesburg, South Africa: a cross-sectional study.

BACKGROUND HIV infection is a known risk factor for cancer but little is known about HIV testing patterns and the burden of HIV infection in cancer patients. We did a cross-sectional analysis to identify predictors of prior HIV testing and to quantify the burden of HIV in black cancer patients in Johannesburg, South Africa. METHODS The Johannesburg Cancer Case-control Study (JCCCS) recruits newly-diagnosed black cancer patients attending public referral hospitals for oncology and radiation therapy in Johannesburg . All adult cancer patients enrolled into the JCCCS from November 2004 to December 2009 and interviewed on previous HIV testing were included in the analysis. Patients were independently tested for HIV-1 using a single ELISA test . The prevalence of prior HIV testing, of HIV infection and of undiagnosed HIV infection was calculated. Multivariate logistic regression models were fitted to identify factors associated with prior HIV testing. RESULTS A total of 5436 cancer patients were tested for HIV of whom 1833[33.7% (95% CI=32.5-35.0)] were HIV-positive. Three-quarters of patients (4092 patients) had ever been tested for HIV. The total prevalence of undiagnosed HIV infection was 11.5% (10.7-12.4) with 34% (32.0-36.3) of the 1833 patients who tested HIV-positive unaware of their infection. Men >49 years [OR 0.49(0.39-0.63)] and those residing in rural areas [OR 0.61(0.39-0.97)] were less likely to have been previously tested for HIV. Men with at least a secondary education [OR 1.79(1.11-2.90)] and those interviewed in recent years [OR 4.13(2.62 - 6.52)] were likely to have prior testing. Women >49 years [OR 0.33(0.27-0.41)] were less likely to have been previously tested for HIV. In women, having children <5 years [OR 2.59(2.04-3.29)], hormonal contraceptive use [OR 1.33(1.09-1.62)], having at least a secondary education [OR:2.08(1.45-2.97)] and recent year of interview [OR 6.04(4.45-8.2)] were independently associated with previous HIV testing. CONCLUSIONS In a study of newly diagnosed black cancer patients in Johannesburg, over a third of HIV-positive patients were unaware of their HIV status. In South Africa black cancer patients should be targeted for opt-out HIV testing.

Brief Report: HIV Testing Among Pregnant Women Who Attend Antenatal Care in Malawi.

Malawi adopted the Option B+ strategy in 2011. Its success in reducing mother-to-child transmission depends on coverage and timing of HIV testing. We assessed HIV status ascertainment and its predictors during pregnancy. HIV status ascertainment was 82.3% (95% confidence interval: 80.2 to 85.9) in the pre-Option B+ period and 85.7% (95% confidence interval: 83.4 to 88.0) in the Option B+ period. Higher HIV ascertainment was independently associated with higher age, attending antenatal care more than once, and registration in 2010. The observed high variability of HIV ascertainment between sites (50.6%-97.7%) and over time suggests that HIV test kit shortages and insufficient numbers of staff posed major barriers to reducing mother-to-child transmission.

Testing the 'Learning for Sustainabiliy' Approach in a Training for Trainers: Contribution to new learning theory and approaches

Mainstreaming the LforS approach is a challenge due to dive rging institutional priorities, customs, and expectations of classically traine d staff. A workshop to test LforS theory and practice, and explore how to mainstream it, took place in a concrete context in a rural district of Mozambique, focusing on agricultural, forest and water resources. The evaluation showed that the principles of interaction applied pe rmitted to link rational know ledge with practical experience through mutual learning and iterative self-reflection. The combination of learning techniques was considered usef ul; participants called for further opportunities to apply the LforS methodology, proposing next steps.

Estimating population and livestock density of mobile pastoralists and sedentary settlements in the southeastern Lake Chad area

Mobile pastoralists provide major contributions to the gross domestic product in Chad, but little information is available regarding their demography. The Lake Chad area population is increasing, resulting in competition for scarce land and water resources. For the first time, the density of people and animals from mobile and sedentary populations was assessed using randomly defined sampling areas. Four sampling rounds were conducted over two years in the same areas to show population density dynamics. We identified 42 villages of sedentary communities in the sampling zones; 11 (in 2010) and 16 (in 2011) mobile pastoralist camps at the beginning of the dry season and 34 (in 2011) and 30 (in 2012) camps at the end of the dry season. A mean of 64.0 people per km2 (95% confidence interval, 20.3-107.8) were estimated to live in sedentary villages. In the mobile communities, we found 5.9 people per km2 at the beginning and 17.5 people per km2 at the end of the dry season. We recorded per km2 on average 21.0 cattle and 31.6 small ruminants in the sedentary villages and 66.1 cattle and 102.5 small ruminants in the mobile communities, which amounts to a mean of 86.6 tropical livestock units during the dry season. These numbers exceed, by up to five times, the published carrying capacities for similar Sahelian zones. Our results underline the need for a new institutional framework. Improved land use management must equally consider the needs of mobile communities and sedentary populations.

EASE: EPC as a service to ease mobile core network deployment over cloud

The objective of this article is to demonstrate the feasibility of on-demand creation of cloud-based elastic mobile core networks, along with their lifecycle management. For this purpose the article describes the key elements to realize the architectural vision of EPC as a Service, an implementation option of the Evolved Packet Core, as specified by 3GPP, which can be deployed in cloud environments. To meet several challenging requirements associated with the implementation of EPC over a cloud infrastructure and providing it “as a Service,” this article presents a number of different options, each with different characteristics, advantages, and disadvantages. A thorough analysis comparing the different implementation options is also presented.

Avalanche related damage potential - changes of persons and mobile values since the mid-twentieth century, case study Galtür

When determining risk related to natural hazard processes, many studies neglect the investigations of the damage potential or are limited to the assessment of immobile values like buildings. However, persons as well as mobile values form an essential part of the damage potential. Knowledge of the maximum number of exposed persons in an endangered area is of great importance for elaborating evacuation plans and immediate measures in case of catastrophes. In addition, motor vehicles can also be highly damaged, as was shown by the analysis of avalanche events. With the removal of mobile values in time as a preventive measure this kind of damage can be minimised. This study presents a method for recording the maximum number of exposed persons and monetarily assessing motor vehicles in the municipality of Galt¨ur (Tyrol, Austria). Moreover, general developments of the damage potential due to significant socio-economic changes since the mid-twentieth century are pointed out in the study area. The present situation of the maximum number of persons and mobile values in the official avalanche hazard zones of the municipality is described in detail. Information on the number of persons is derived of census data, tourism and employment statistics. During the winter months, a significant increase overlaid by strong short-term fluctuation in the number of persons can be noted. These changes result from a higher demand of tourism related manpower as well as from varying occupancy rates. The number of motor vehicles in endangered areas is closely associated to the number of exposed persons. The potential number of motor vehicles is investigated by means of mapping, statistics on the stock of motor vehicles and the density distribution. Diurnal and seasonal fluctuations of the investigated damage potential are pointed out. The recording of the number of persons and mobile values in endangered areas is vital for any disaster management.

A Tutorial of the Mobile Multimedia Wireless Sensor Network (M3WSN) OMNeT++ Framework

In this work, we will give a detailed tutorial instruction about how to use the Mobile Multi-Media Wireless Sensor Networks (M3WSN) simulation framework. The M3WSN framework has been published as a scientific paper in the 6th International Workshop on OMNeT++ (2013) [1]. M3WSN framework enables the multimedia transmission of real video se- quence. Therefore, a set of multimedia algorithms, protocols, and services can be evaluated by using QoE metrics. Moreover, key video-related information, such as frame types, GoP length and intra-frame dependency can be used for creating new assessment and optimization solutions. To support mobility, M3WSN utilizes different mobility traces to enable the understanding of how the network behaves under mobile situations. This tutorial will cover how to install and configure the M3WSN framework, setting and running the experiments, creating mobility and video traces, and how to evaluate the performance of different protocols. The tutorial will be given in an environment of Ubuntu 12.04 LTS and OMNeT++ 4.2.

Feasibility of cardiopulmonary exercise testing and training using a robotics-assisted tilt table in dependent-ambulatory stroke patients

BACKGROUND: We evaluated the feasibility of an augmented robotics-assisted tilt table (RATT) for incremental cardiopulmonary exercise testing (CPET) and exercise training in dependent-ambulatory stroke patients. METHODS: Stroke patients (Functional Ambulation Category ≤ 3) underwent familiarization, an incremental exercise test (IET) and a constant load test (CLT) on separate days. A RATT equipped with force sensors in the thigh cuffs, a work rate estimation algorithm and real-time visual feedback to guide the exercise work rate was used. Feasibility assessment considered technical feasibility, patient tolerability, and cardiopulmonary responsiveness. RESULTS: Eight patients (4 female) aged 58.3 ± 9.2 years (mean ± SD) were recruited and all completed the study. For IETs, peak oxygen uptake (V'O2peak), peak heart rate (HRpeak) and peak work rate (WRpeak) were 11.9 ± 4.0 ml/kg/min (45 % of predicted V'O2max), 117 ± 32 beats/min (72 % of predicted HRmax) and 22.5 ± 13.0 W, respectively. Peak ratings of perceived exertion (RPE) were on the range "hard" to "very hard". All 8 patients reached their limit of functional capacity in terms of either their cardiopulmonary or neuromuscular performance. A ventilatory threshold (VT) was identified in 7 patients and a respiratory compensation point (RCP) in 6 patients: mean V'O2 at VT and RCP was 8.9 and 10.7 ml/kg/min, respectively, which represent 75 % (VT) and 85 % (RCP) of mean V'O2peak. Incremental CPET provided sufficient information to satisfy the responsiveness criteria and identification of key outcomes in all 8 patients. For CLTs, mean steady-state V'O2 was 6.9 ml/kg/min (49 % of V'O2 reserve), mean HR was 90 beats/min (56 % of HRmax), RPEs were > 2, and all patients maintained the active work rate for 10 min: these values meet recommended intensity levels for bouts of training. CONCLUSIONS: The augmented RATT is deemed feasible for incremental cardiopulmonary exercise testing and exercise training in dependent-ambulatory stroke patients: the approach was found to be technically implementable, acceptable to the patients, and it showed substantial cardiopulmonary responsiveness. This work has clinical implications for patients with severe disability who otherwise are not able to be tested.

Testing "saintly" authenticity - Investigations on two catacomb saints

The goal of this study was to examine two catacomb saints from Switzerland with conventional radiographic imaging and minimally invasive techniques to test their authenticity.