Adverse events in clinical treatments with serotonergic psychedelics and MDMA:A mixed-methods systematic review

Introduction: Small-scale clinical studies with psychedelic drugs have shown promising results for the treatment of several mental disorders. Before psychedelics become registered medicines, it is important to know the full range of adverse events (AEs) for making balanced treatment decisions. Objective: To systematically review the presence of AEs during and after administration of serotonergic psychedelics and 3,4-methyenedioxymethamphetamine (MDMA) in clinical studies. Methods: We systematically searched PubMed, PsycINFO, Embase, and ClinicalTrials.gov for clinical trials with psychedelics since 2000 describing the results of quantitative and qualitative studies. Results: We included 44 articles (34 quantitative + 10 qualitative), describing treatments with MDMA and serotonergic psychedelics (psilocybin, lysergic acid diethylamide, and ayahuasca) in 598 unique patients. In many studies, AEs were not systematically assessed. Despite this limitation, treatments seemed to be overall well tolerated. Nausea, headaches, and anxiety were commonly reported acute AEs across diagnoses and compounds. Late AEs included headaches (psilocybin, MDMA), fatigue, low mood, and anxiety (MDMA). One serious AE occurred during MDMA administration (increase in premature ventricular contractions requiring brief hospitalization); no other AEs required medical intervention. Qualitative studies suggested that psychologically challenging experiences may also be therapeutically beneficial. Except for ayahuasca, a large proportion of patients had prior experience with psychedelic drugs before entering studies. Conclusions: AEs are poorly defined in the context of psychedelic treatments and are probably underreported in the literature due to study design (lack of systematic assessment of AEs) and sample selection. Acute challenging experiences may be therapeutically meaningful, but a better understanding of AEs in the context of psychedelic treatments requires systematic and detailed reporting

Stability of chronotype over a 7-year follow-up period and its association with severity of depressive and anxiety symptoms

Background: Chronotype is an individual's preferred timing of sleep and activity, and is often referred to as a later chronotype (or evening-type) or an earlier chronotype (or morning-type). Having an evening chronotype is associated with more severe depressive and anxiety symptoms. Based on these findings it is has been suggested that chronotype is a stable construct associated with vulnerability to develop depressive or anxiety disorders. To examine this, we test the stability of chronotype over 7 years, and its longitudinal association with the change in severity of depressive and anxiety symptoms. Methods: Data of 1,417 participants with a depressive and/or anxiety disorder diagnosis and healthy controls assessed at the 2 and 9-year follow-up waves of the Netherlands Study of depression and anxiety were used. Chronotype was assessed with the Munich chronotype questionnaire. Severity of depressive and anxiety symptoms were assessed with the inventory of depressive symptomatology and Beck anxiety inventory. Results: Chronotype was found to be moderately stable (r = 0.53) and on average advanced (i.e., became earlier) with 10.8 min over 7 years (p <.001). Controlling for possible confounders, a decrease in severity of depressive symptoms was associated with an advance in chronotype (B = 0.008, p =.003). A change in severity of anxiety symptoms was not associated with a change in chronotype. Conclusion: Chronotype was found to be a stable, trait-like construct with only a minor level advance over a period of 7 years. The change in chronotype was associated with a change in severity of depressive, but not anxiety, symptoms

Ultraviolet Signatures of Tidal Interaction in the Giant Spiral Galaxy, M101

We present new evidence for tidal interactions having occurred in the disk of M101 in the last 10^8 - 10^9 years. Recent imaging of the far-ultraviolet emission from M101 by the Shuttle-borne Ultraviolet Imaging Telescope (UIT) reveals with unprecedented clarity a disk-wide pattern of multiple linear arm segments (``crooked arms''). The deep FUV image also shows a faint outer spiral arm with a (``curly tail'') feature that appears to loop around the supergiant HII region NGC 5471 - linking this outlying starburst with the rest of the galaxy. These FUV-bright features most likely trace hot O & B-type stars along with scattered light from associated nebular dust. Counterparts of the outermost ``crooked arms'' are evident in maps at visible wavelengths and in the 21-cm line of HI. The inner-disk FUV arms are most closely associated with H$\alpha$ knots and the outer (downstream) sides of CO arms. Comparisons of the ``crooked arm'' and ``curly tail'' morphologies with dynamical simulations yield the greatest similitude, when the non- axisymmetric forcing comes from a combination of ``external interactions'' with one or more companion galaxies and ``internal perturbations'' from massive objects orbiting within the disk. We speculate that NGC 5471 represents one of these ``massive disturbers'' within the disk, whose formation followed from a tidal interaction between M101 and a smaller galaxy.Comment: Paper format (latex); length of paper (8); 4 gif figure files; uses aas2pp4.sty AASTeX macro file; to be published in Part I of the Astrophysical Journa

Star Formation Thresholds in Galactic Disks

We report the first results of a detailed study of the star formation law in a sample of 32 nearby spiral galaxies with well-measured rotation curves, HI and H$_2$ (as traced by CO) surface density profiles, and new \Ha CCD photometry. Our results strongly support the view that the formation of gravitationally bound interstellar clouds regulates the onset of widespread star formation -- at least in the outer regions of galactic disks.Comment: Will appear in July 1 ApJ. Abbreviated abstract. Postscript version available at http://www.astro.caltech.edu/~clm

Selective blockade of interferon-α and -β reveals their non-redundant functions in a mouse model of West Nile virus infection

Although type I interferons (IFNs) were first described almost 60 years ago, the ability to monitor and modulate the functional activities of the individual IFN subtypes that comprise this family has been hindered by a lack of reagents. The major type I IFNs, IFN-β and the multiple subtypes of IFN-α, are expressed widely and induce their effects on cells by interacting with a shared heterodimeric receptor (IFNAR). In the mouse, the physiologic actions of IFN-α and IFN-β have been defined using polyclonal anti-type I IFN sera, by targeting IFNAR using monoclonal antibodies or knockout mice, or using Ifnb-/- mice. However, the corresponding analysis of IFN-α has been difficult because of its polygenic nature. Herein, we describe two monoclonal antibodies (mAbs) that differentially neutralize murine IFN-β or multiple subtypes of murine IFN-α. Using these mAbs, we distinguish specific contributions of IFN-β versus IFN-α in restricting viral pathogenesis and identify IFN-α as the key mediator of the antiviral response in mice infected with West Nile virus. This study thus suggests the utility of these new reagents in dissecting the antiviral and immunomodulatory roles of IFN-β versus IFN-α in murine models of infection, immunity, and autoimmunity

Detection and localization of early- and late-stage cancers using platelet RNA

Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I–IV cancer patients and in half of 352 stage I–III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening

American College of Rheumatology Provisional Criteria for Clinically Relevant Improvement in Children and Adolescents With Childhood-Onset Systemic Lupus Erythematosus

10.1002/acr.23834ARTHRITIS CARE & RESEARCH715579-59

THINGS: The HI Nearby Galaxy Survey

Original article can be found at: http://www.iop.org/EJ/journal/aj Copyright American Astronomical Society DOI: 10.1088/0004-6256/136/6/2563We present “The HI Nearby Galaxy Survey (THINGS)”, a high spectral (≤5.2 kms−1) and spatial (~ 6′′) resolution survey of HI emission in 34 nearby galaxies obtained using the NRAO Very Large Array (VLA). The overarching scientific goal of THINGS is to investigate fundamental characteristics of the interstellar medium (ISM) related to galaxy morphology, star formation and mass distribution across the Hubble sequence. Unique characteristics of the THINGS database are the homogeneous sensitivity as well as spatial and velocity resolution of the HI data which is at the limit of what can be achieved with the VLA for a significant number of galaxies.Peer reviewe

Combined dietary folate, vitamin B-12, and vitamin B-6 intake influences plasma docosahexaenoic acid concentration in rats

<p>Abstract</p> <p>Background</p> <p>Folate, vitamin B-12, and vitamin B-6 are essential nutritional components in one-carbon metabolism and are required for methylation capacity. The availability of these vitamins may therefore modify methylation of phosphatidylethanolamine (PE) to phosphatidylcholine (PC) by PE-<it>N</it>-methyltransferase (PEMT) in the liver. It has been suggested that PC synthesis by PEMT plays an important role in the transport of polyunsaturated fatty acids (PUFAs) like docosahexaenoic acid (DHA) from the liver to plasma and possibly other tissues. We hypothesized that if B-vitamin supplementation enhances PEMT activity, then supplementation could also increase the concentration of plasma levels of PUFAs such as DHA. To test this hypothesis, we determined the effect of varying the combined dietary intake of these three B-vitamins on plasma DHA concentration in rats.</p> <p>Methods</p> <p>In a first experiment, plasma DHA and plasma homocysteine concentrations were measured in rats that had consumed a B-vitamin-poor diet for 4 weeks after which they were either continued on the B-vitamin-poor diet or switched to a B-vitamin-enriched diet for another 4 weeks. In a second experiment, plasma DHA and plasma homocysteine concentrations were measured in rats after feeding them one of four diets with varying levels of B-vitamins for 4 weeks. The diets provided 0% (poor), 100% (normal), 400% (enriched), and 1600% (high) of the laboratory rodent requirements for each of the three B-vitamins.</p> <p>Results</p> <p>Plasma DHA concentration was higher in rats fed the B-vitamin-enriched diet than in rats that were continued on the B-vitamin-poor diet (<it>P</it> = 0.005; experiment A). Varying dietary B-vitamin intake from deficient to supra-physiologic resulted in a non-linear dose-dependent trend for increasing plasma DHA (<it>P</it> = 0.027; experiment B). Plasma DHA was lowest in rats consuming the B-vitamin-poor diet (<it>P</it> > 0.05 vs<it>.</it> normal, <it>P</it> < 0.05 vs<it>.</it> enriched and high) and highest in rats consuming the B-vitamin-high diet (<it>P</it> < 0.05 vs<it>.</it> poor and normal, <it>P</it> > 0.05 vs<it>.</it> enriched). B-vitamin deficiency significantly increased plasma total homocysteine but increasing intake above normal did not significantly reduce it. Nevertheless, in both experiments plasma DHA was inversely correlated with plasma total homocysteine.</p> <p>Conclusion</p> <p>These data demonstrate that dietary folate, vitamin B-12, and vitamin B-6 intake can influence plasma concentration of DHA.</p