Efficacy and safety of Cannabidiol and Tetrahydrocannabivarin on glycemic and lipid parameters in patients with Type 2 diabetes: a randomized, double-blind, placebo-controlled, parallel group pilot study

OBJECTIVE Cannabidiol (CBD) and Δ9-tetrahydrocannabivarin (THCV) are nonpsychoactive phytocannabinoids affecting lipid and glucose metabolism in animal models. This study set out to examine the effects of these compounds in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS In this randomized, double-blind, placebo-controlled study, 62 subjects with noninsulin-treated type 2 diabetes were randomized to five treatment arms: CBD (100 mg twice daily), THCV (5 mg twice daily), 1:1 ratio of CBD and THCV (5 mg/5 mg, twice daily), 20:1 ratio of CBD and THCV (100 mg/5 mg, twice daily), or matched placebo for 13 weeks. The primary end point was a change in HDL-cholesterol concentrations from baseline. Secondary/tertiary end points included changes in glycemic control, lipid profile, insulin sensitivity, body weight, liver triglyceride content, adipose tissue distribution, appetite, markers of inflammation, markers of vascular function, gut hormones, circulating endocannabinoids, and adipokine concentrations. Safety and tolerability end points were also evaluated. RESULTS Compared with placebo, THCV significantly decreased fasting plasma glucose (estimated treatment difference [ETD] = −1.2 mmol/L; P < 0.05) and improved pancreatic β-cell function (HOMA2 β-cell function [ETD = −44.51 points; P < 0.01]), adiponectin (ETD = −5.9 × 106 pg/mL; P < 0.01), and apolipoprotein A (ETD = −6.02 μmol/L; P < 0.05), although plasma HDL was unaffected. Compared with baseline (but not placebo), CBD decreased resistin (−898 pg/ml; P < 0.05) and increased glucose-dependent insulinotropic peptide (21.9 pg/ml; P < 0.05). None of the combination treatments had a significant impact on end points. CBD and THCV were well tolerated. CONCLUSIONS THCV could represent a new therapeutic agent in glycemic control in subjects with type 2 diabetes

Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning

Understanding the genomic basis of memory processes may help in combating neurodegenerative disorders. Hence, we examined the associations of common genetic variants with verbal short-term memory and verbal learning in adults without dementia or stroke (N = 53,637). We identified novel loci in the intronic region of CDH18, and at 13q21 and 3p21.1, as well as an expected signal in the APOE/APOC1/TOMM40 region. These results replicated in an independent sample. Functional and bioinformatic analyses supported many of these loci and further implicated POC1. We showed that polygenic score for verbal learning associated with brain activation in right parieto-occipital region during working memory task. Finally, we showed genetic correlations of these memory traits with several neurocognitive and health outcomes. Our findings suggest a role of several genomic loci in verbal memory processes

The evolution of the red sequence slope in massive galaxy clusters

We investigate the evolution of the optical and near-infrared colour-magnitude relation in an homogeneous sample of massive clusters from z = 1 to the present epoch. By comparing deep Hubble Space Telescope ACS imaging of X-ray selected MACS survey clusters at z = 0.5 to the similarly selected LARCS sample at z = 0.1 we find that the rest-frame d(U -V)/dV slope of the colour-magnitude relation evolves with redshift which we attribute to the build up of the red sequence over time. This rest frame slope evolution is not adequately reproduced by that predicted from semi-analytic models based on the Millennium Simulation despite a prescription for the build up of the red sequence by in-falling galaxies, 'strangulation'. We observe no strong correlation between this slope and the cluster environment at a given redshift demonstrating that the observed evolution is not due to a secondary correlation. Also presented are near-infrared UKIRT WFCAM observations of the LARCS clusters which confirm and improve on the the result from Stott et al. (2007) finding that there has been a two-fold increase in faint MV > -20 galaxies on the red sequence since z = 0.5 to a significance of 5sigma.Comment: MNRAS accepte

An Increase in the Faint Red Galaxy Population in Massive Clusters since z \~ 0.5

We compare the luminosity functions for red galaxies lying on the rest-frame (U - V) color-magnitude sequence in a homogeneous sample of 10 X-ray-luminous clusters from the MACS survey at z ~ 0.5 to a similarly selected X-ray cluster sample at z ~ 0.1. We exploit deep Hubble Space Telescope ACS imaging in the F555W and F814W passbands of the central 1.2 Mpc diameter regions of the distant clusters to measure precise colors for the galaxies in these regions and statistically correct for contamination by field galaxies using observations of blank fields. We apply an identical analysis to ground-based photometry of the z ~ 0.1 sample. This comparison demonstrates that the number of faint, MV ~ -19, red galaxies relative to the bright population seen in the central regions of massive clusters has roughly doubled over the 4 Gyr between z ~ 0.5 and z ~ 0.1. We quantify this difference by measuring the dwarf-giant ratio on the red sequence, which increases by a factor of at least 2.2 ± 0.4 since z ~ 0.5. This is consistent with the idea that many faint, blue, star-forming galaxies in high-density environments are transforming onto the red sequence in the last half of the Hubble time

Properties of proxy-derived modified Rankin scale assessment

&lt;p&gt;Background: Cognitive or communication issues may preclude direct modified Rankin Scale interview, necessitating interview with a suitable surrogate. The clinimetric properties of this proxy modified Rankin Scale assessment have not been described.&lt;/p&gt; &lt;p&gt;Aims: To describe reliability of proxy-derived modified Rankin Scale and compare with traditional direct patient interview.&lt;/p&gt; &lt;p&gt;Methods: Researchers assessed consenting stroke inpatients and their proxies using a nonstructured modified Rankin Scale approach. Paired interviewers (trained in modified Rankin Scale) performed independent and blinded modified Rankin Scale assessment of patients and appropriate proxies. Interobserver variability and agreement between patient and proxy modified Rankin Scale were described using kappa statistics (k, 95% confidence interval) and percentage agreement.&lt;/p&gt; &lt;p&gt;Results: Ninety-seven stroke survivors were assessed. Proxies were family members (n = 29), nurses (n = 50), or physiotherapists (n = 25). Median modified Rankin Scale from both patient and proxies was 3 [interquartile range (IQR): 2-4]. Reliability for patient modified Rankin Scale interview was weighted kappa = 0·70 (95% confidence interval: 0·30–1·00). Reliability for proxy modified Rankin Scale weighted kappa = 0·62 (95% confidence interval: 0·34–0·90). Subgroup analysis of various proxy information sources were as follows: family weighted kappa = 0·61; nurse weighted kappa = 0·58; therapist weighted kappa = 0·58. There was disagreement between patient-derived modified Rankin Scale and corresponding proxy modified Rankin Scale weighted kappa = 0·64 (95% CI: 0·42–0·86).&lt;/p&gt; &lt;p&gt;Conclusions: There is potential for substantial interobserver variability in proxy modified Rankin Scale and validity of certain proxy assessments is questionable. Direct modified Rankin Scale interview is preferred.&lt;/p&gt

Carbon dynamics in a model grassland with functionally different soil communities

1. Impacts of environmental changes on carbon cycling in terrestrial ecosystems are typically correlated with shifts in the composition, biomass and activity of soil faunal communities. Given the role of soil fauna in decomposition, shifts in soil faunal communities may further modify the carbon dynamics of a perturbed system. 2. To test this possibility, we manipulated soil community composition in model grassland ecosystems and used a 13CO2-tracer to follow the assimilation, retention and pathways of recent, photosynthetically fixed carbon. The community treatments formed a nested hierarchy of functional complexity: (1) microbiota only; (2) microbiota and mesofauna; (3) microbiota, mesofauna and macrofauna. 3. These treatments significantly affected the rate of decline in 13C-label respiration rate and the amount of 13C-label retained by the communities: while the rate of decline in 13C-label respiration rate was greatest in the microbiota treatment, the treatment with both micro- and mesofauna retained less 13C-label than either the more functionally complex or simple treatments. The presence of macrofauna altered the utilization of 13C-label by Collembola and Enchytraeidae: they decreased the mass of 13C-label utilized by Collembola and increased that utilized by Enchytraeidae. 4. Our results suggest that soil community composition may play a key role in regulating the dynamics of recent, photosynthetically fixed carbon