Results of an international drug testing service for cryptomarket users

Introduction: User surveys indicate that expectations of higher drug purity are a key reason for cryptomarket use. In 2014-2015, Spain's NGO Energy Control conducted a 1-year pilot project to provide a testing service to cryptomarket drug users using the Transnational European Drug Information (TEDI) guidelines. In this paper, we present content and purity data from the trial. Methods: 219 samples were analyzed by gas chromatography associated with mass spectrometry (GC/MS). Users were asked to report what substance they allegedly purchased. Results: 40 different advertised substances were reported, although 77.6% were common recreational drugs (cocaine, MDMA, amphetamines, LSD, ketamine, cannabis). In 200 samples (91.3%), the main result of analysis matched the advertised substance. Where the advertised compound was detected, purity levels (m. ±. SD) were: cocaine 71.6. ±. 19.4%; MDMA (crystal) 88.3. ±. 1.4%; MDMA (pills) 133.3. ±. 38.4. mg; Amphetamine (speed) 51.3. ±. 33.9%; LSD 123.6. ±. 40.5. µg; Cannabis resin THC: 16.5. ±. 7.5% CBD: 3.4. ±. 1.5%; Ketamine 71.3. ±. 38.4%. 39.8% of cocaine samples contained the adulterant levamisole (11.6. ±. 8%). No adulterants were found in MDMA and LSD samples. Discussion: The largest collection of test results from drug samples delivered from cryptomarkets are reported in this study. Most substances contained the advertised ingredient and most samples were of high purity. The representativeness of these results is unknown

Ultrasound measurement of the effects of high, medium and low hip long-axis distraction mobilization forces on the joint space width and its correlation with the joint strain

Background: No study has evaluated the mechanical effect of different magnitudes of long axis-distraction mobilization (LADM) force on hip joint space width (JSW) or the association between the separation of joint surfaces and the strain on hip capsular ligaments. Objective: To compare the joint separation when applying three different magnitudes of LADM forces (low, medium and high) and to analyse the correlation between joint separation, strain on the inferior ilio-femoral ligament and magnitude of applied force. Design: Repeated measures controlled laboratory cadaveric study. Methods: Three magnitudes of force were applied to 11 cadaveric hip joints (mean age 73 years). Ultrasound images were used to measure joint separation, and strain gauges recorded inferior ilio-femoral ligament strain during each condition. Results: The magnitude of joint separation was significantly different between low (0.23 ± 0.19 mm), medium (0.72 ± 0.22 mm) and high (2.62 ± 0.43 mm) forces (p 0.723; p < 0.001). Conclusion: Hip joint separation and ligament strain during LADM are associated with the magnitude of the applied force

Dissect: detection and characterization of novel structural alterations in transcribed sequences

Motivation: Computational identification of genomic structural variants via high-throughput sequencing is an important problem for which a number of highly sophisticated solutions have been recently developed. With the advent of high-throughput transcriptome sequencing (RNA-Seq), the problem of identifying structural alterations in the transcriptome is now attracting significant attention

Health and social problems associated with recent Novel Psychoactive Substance (NPS) use amongst marginalised, nightlife and online users in six European countries.

Continued diversification and use of new psychoactive substances (NPS) across Europe remains a public health challenge. The study describes health and social consequences of recent NPS use as reported in a survey of marginalised, nightlife and online NPS users in the Netherlands, Hungary, Portugal, Ireland, Germany and Poland (n = 3023). Some respondents were unable to categorise NPS they had used. Use of ‘herbal blends’ and ‘synthetic cannabinoids obtained pure’ was most reported in Germany, Poland and Hungary, and use of ‘branded stimulants’ and ‘stimulants/empathogens/nootropics obtained pure’ was most reported in the Netherlands. Increased heart rate and palpitation, dizziness, anxiety, horror trips and headaches were most commonly reported acute side effects. Marginalised users reported substantially more acute side effects, more mid- and long-term mental and physical problems, and more social problems. Development of country-specific NPS awareness raising initiatives, health and social service needs assessments, and targeted responses are warranted

The Dynamic Landscape of Novel Psychoactive Substance (NPS) Use in Ireland: Results from an Expert Consultation

In Ireland, legislators encountered a new phenomenon in 2005 onwards with the advent of ‘legal highs’ sold in headshops. Use of ‘legal highs’ containing herbal and synthetic new psychoactive substances (NPS) was not confined to problematic drug users, and included social recreational users. Legislative controls were enacted in 2010, 2011 and 2015. The study aimed to investigate expert perspectives on the NPS situation with regard to changing and emergent trends in use, health and social consequences and service implications. This brief report presents descriptive findings from a national consultation using a structured guide with experts in 2016. Four themes emerged and centred on; ‘Definitions of NPS used within Professional Roles’; ‘Professional Experiences of NPS‘; ‘Types of NPS Users, Sourcing and Consequences of Use’; and ‘Service Response.’ Findings underscored the mental health and addiction related consequences of NPS use, with prevention, clinical and treatment services ill- equipped to deal with the particular characteristics of this form of drug abuse. Enhanced strategies, services and clinical responses are warranted to address the challenges encountered. © 2016 Springer Science+Business Media New Yor

Controlled Chaos of Polymorphic Mucins in a Metazoan Parasite (Schistosoma mansoni) Interacting with Its Invertebrate Host (Biomphalaria glabrata)

Invertebrates were long thought to possess only a simple, effective and hence non-adaptive defence system against microbial and parasitic attacks. However, recent studies have shown that invertebrate immunity also relies on immune receptors that diversify (e.g. in echinoderms, insects and mollusks (Biomphalaria glabrata)). Apparently, individual or population-based polymorphism-generating mechanisms exists that permit the survival of invertebrate species exposed to parasites. Consequently, the generally accepted arms race hypothesis predicts that molecular diversity and polymorphism also exist in parasites of invertebrates. We investigated the diversity and polymorphism of parasite molecules (Schistosoma mansoni Polymorphic Mucins, SmPoMucs) that are key factors for the compatibility of schistosomes interacting with their host, the mollusc Biomphalaria glabrata. We have elucidated the complex cascade of mechanisms acting both at the genomic level and during expression that confer polymorphism to SmPoMuc. We show that SmPoMuc is coded by a multi-gene family whose members frequently recombine. We show that these genes are transcribed in an individual-specific manner, and that for each gene, multiple splice variants exist. Finally, we reveal the impact of this polymorphism on the SmPoMuc glycosylation status. Our data support the view that S. mansoni has evolved a complex hierarchical system that efficiently generates a high degree of polymorphism—a “controlled chaos”—based on a relatively low number of genes. This contrasts with protozoan parasites that generate antigenic variation from large sets of genes such as Trypanosoma cruzi, Trypanosoma brucei and Plasmodium falciparum. Our data support the view that the interaction between parasites and their invertebrate hosts are far more complex than previously thought. While most studies in this matter have focused on invertebrate host diversification, we clearly show that diversifying mechanisms also exist on the parasite side of the interaction. Our findings shed new light on how and why invertebrate immunity develops

Interplay between Exonic Splicing Enhancers, mRNA Processing, and mRNA Surveillance in the Dystrophic Mdx Mouse

BACKGROUND: Pre-mRNA splicing, the removal of introns from RNA, takes place within the spliceosome, a macromolecular complex composed of five small nuclear RNAs and a large number of associated proteins. Spliceosome assembly is modulated by the 5′ and 3′ splice site consensus sequences situated at the ends of each intron, as well as by exonic and intronic splicing enhancers/silencers recognized by SR and hnRNP proteins. Nonsense mutations introducing a premature termination codon (PTC) often result in the activation of cellular quality control systems that reduce mRNA levels or alter the mRNA splicing pattern. The mdx mouse, a commonly used genetic model for Duchenne muscular dystrophy (DMD), lacks dystrophin by virtue of a premature termination codon (PTC) in exon 23 that also severely reduces the level of dystrophin mRNA. However, the effect of the mutation on dystrophin RNA processing has not yet been described. METHODOLOGY/PRINCIPAL FINDING: Using combinations of different biochemical and cellular assays, we found that the mdx mutation partially disrupts a multisite exonic splicing enhancer (ESE) that is recognized by a 40 kDa SR protein. In spite of the presence of an inefficient intron 22 3′ splice site containing the rare GAG triplet, the mdx mutation does not activate nonsense-associated altered splicing (NAS), but induces exclusively nonsense-mediated mRNA decay (NMD). Functional binding sites for SR proteins were also identified in exon 22 and 24, and in vitro experiments show that SR proteins can mediate direct association between exon 22, 23, and 24. CONCLUSIONS/SIGNIFICANCE: Our findings highlight the complex crosstalk between trans-acting factors, cis-elements and the RNA surveillance machinery occurring during dystrophin mRNA processing. Moreover, they suggest that dystrophin exon–exon interactions could play an important role in preventing mdx exon 23 skipping, as well as in facilitating the pairing of committed splice sites