Home Manufacture of Drugs: An Online Investigation and a Toxicological Reality Check of Online Discussions on Drug Chemistry

Emerging trends in market dynamics and the use of new psychoactive substances are both a public health concern and a complex regulatory issue. One novel area of investigation is the availability of homemade opioids, amphetamines and dissociatives, and the potential fueling of interest in clandestine home manufacture of drugs via the Internet. We illustrate here how online communal folk pharmacology of homemade drugs on drug website forums may actually inform home manufacture practices or contribute to the reduction of harms associated with this practice. Discrepancies between online information around purification and making homemade drugs safer, and the synthesis of the same substances in a proper laboratory environment, exist. Moderation and shutdown of synthesis queries and discussions online are grounded in drug websites adhering to harm-reduction principles by facilitating discussions around purification of homemade drugs only. Drug discussion forums should consider reevaluating their policies on chemistry discussions in aiming to reach people who cannot or will not refrain from cooking their own drugs with credible information that may contribute to reductions in the harms associated with this practice. © 2017 Taylor & Francis Group, LL

Mass measurements near the rr-process path using the Canadian Penning Trap mass spectrometer

The masses of 40 neutron-rich nuclides from Z = 51 to 64 were measured at an average precision of $\delta m/m= 10^{-7}$ using the Canadian Penning Trap mass spectrometer at Argonne National Laboratory. The measurements, of fission fragments from a $^{252}$Cf spontaneous fission source in a helium gas catcher, approach the predicted path of the astrophysical $r$ process. Where overlap exists, this data set is largely consistent with previous measurements from Penning traps, storage rings, and reaction energetics, but large systematic deviations are apparent in $\beta$-endpoint measurements. Differences in mass excess from the 2003 Atomic Mass Evaluation of up to 400 keV are seen, as well as systematic disagreement with various mass models.Comment: 15 pages, 16 figures. v2 updated, published in Physical Review

β-delayed neutron spectroscopy using trapped radioactive ions

A novel technique for β-delayed neutron spectroscopy has been demonstrated using trapped ions. The neutron-energy spectrum is reconstructed by measuring the time of flight of the nuclear recoil following neutron emission, thereby avoiding all the challenges associated with neutron detection, such as backgrounds from scattered neutrons and γ rays and complicated detector-response functions. I+137 ions delivered from a Cf252 source were confined in a linear Paul trap surrounded by radiation detectors, and the β-delayed neutron-energy spectrum and branching ratio were determined by detecting the β- and recoil ions in coincidence. Systematic effects were explored by determining the branching ratio three ways. Improvements to achieve higher detection efficiency, better energy resolution, and a lower neutron-energy threshold are proposed. © 2013 American Physical Society

Tensor interaction limit derived from the α-β-ν̄ correlation in trapped Li8 ions

A measurement of the α-β-ν̄ angular correlation in the Gamow-Teller decay Li8→Be*8+ν̄+β, Be*8→ α+α has been performed using ions confined in a linear Paul trap surrounded by silicon detectors. The energy difference spectrum of the α particles emitted along and opposite the direction of the β particle is consistent with the standard model prediction and places a limit of 3.1% (95.5% confidence level) on any tensor contribution to the decay. From this result, the amplitude of any tensor component CT relative to that of the dominant axial-vector component CA of the electroweak interaction is limited to |CT/CA|\u3c0.18 (95.5% confidence level). This experimental approach is facilitated by several favorable features of the Li8 β decay and has different systematic effects than the previous β-ν̄ correlation results for a pure Gamow-Teller transition obtained from studying He6 β decay. © 2013 American Physical Society

Limit on Tensor Currents from Li 8 β Decay

In the standard model, the weak interaction is formulated with a purely vector-axial-vector (V-A) structure. Without restriction on the chirality of the neutrino, the most general limits on tensor currents from nuclear β decay are dominated by a single measurement of the β-ν¯ correlation in He6 β decay dating back over a half century. In the present work, the β-ν¯-α correlation in the β decay of Li8 and subsequent α-particle breakup of the Be8∗ daughter was measured. The results are consistent with a purely V-A interaction and in the case of couplings to right-handed neutrinos (CT=-CT′) limits the tensor fraction to |CT/CA|2\u3c0.011 (95.5% C.L.). The measurement confirms the He6 result using a different nuclear system and employing modern ion-trapping techniques subject to different systematic uncertainties

Hotspot SF3B1 mutations induce metabolic reprogramming and vulnerability to serine deprivation.

Cancer-associated mutations in the spliceosome gene SF3B1 create a neomorphic protein that produces aberrant mRNA splicing in hundreds of genes, but the ensuing biologic and therapeutic consequences of this missplicing are not well understood. Here we have provided evidence that aberrant splicing by mutant SF3B1 altered the transcriptome, proteome, and metabolome of human cells, leading to missplicing-associated downregulation of metabolic genes, decreased mitochondrial respiration, and suppression of the serine synthesis pathway. We also found that mutant SF3B1 induces vulnerability to deprivation of the nonessential amino acid serine, which was mediated by missplicing-associated downregulation of the serine synthesis pathway enzyme PHGDH. This vulnerability was manifest both in vitro and in vivo, as dietary restriction of serine and glycine in mice was able to inhibit the growth of SF3B1MUT xenografts. These findings describe a role for SF3B1 mutations in altered energy metabolism, and they offer a new therapeutic strategy against SF3B1MUT cancers

Phenotypic and Functional Properties of Helios+ Regulatory T Cells

Helios, an Ikaros family transcription factor, is preferentially expressed at the mRNA and protein level in regulatory T cells. Helios expression previously appeared to be restricted to thymic-derived Treg. Consistent with recent data, we show here that Helios expression is inducible in vitro under certain conditions. To understand phenotypic and functional differences between Helios+ and Helios− Treg, we profiled cell-surface markers of FoxP3+ Treg using unmanipulated splenocytes. We found that CD103 and GITR are expressed at high levels on a subset of Helios+ Treg and that a Helios+ Treg population could be significantly enriched by FACS sorting using these two markers. Quantitative real-time PCR (qPCR) analysis revealed increased TGF-β message in Helios+ Treg, consistent with the possibility that this population possesses enhanced regulatory potential. In tumor-bearing mice, we found that Helios+ Treg were relatively over-represented in the tumor-mass, and BrdU studies showed that, in vivo, Helios+ Treg proliferated more than Helios− Treg. We hypothesized that Helios-enriched Treg might exert increased suppressive effects. Using in vitro suppression assays, we show that Treg function correlates with the absolute number of Helios+ cells in culture. Taken together, these data show that Helios+ Treg represent a functional subset with associated CD103 and GITR expression

Magnetic Resonance Thermometry at 7T for Real-Time Monitoring and Correction of Ultrasound Induced Mild Hyperthermia

While Magnetic Resonance Thermometry (MRT) has been extensively utilized for non-invasive temperature measurement, there is limited data on the use of high field (≥7T) scanners for this purpose. MR-guided Focused Ultrasound (MRgFUS) is a promising non-invasive method for localized hyperthermia and drug delivery. MRT based on the temperature sensitivity of the proton resonance frequency (PRF) has been implemented in both a tissue phantom and in vivo in a mouse Met-1 tumor model, using partial parallel imaging (PPI) to speed acquisition. An MRgFUS system capable of delivering a controlled 3D acoustic dose during real time MRT with proportional, integral, and derivative (PID) feedback control was developed and validated. Real-time MRT was validated in a tofu phantom with fluoroptic temperature measurements, and acoustic heating simulations were in good agreement with MR temperature maps. In an in vivo Met-1 mouse tumor, the real-time PID feedback control is capable of maintaining the desired temperature with high accuracy. We found that real time MR control of hyperthermia is feasible at high field, and k-space based PPI techniques may be implemented for increasing temporal resolution while maintaining temperature accuracy on the order of 1°C

Perzentile für den Body-mass-Index für das Kindes- und Jugendalter unter Heranziehung verschiedener deutscher Stichproben

Fragestellung: Sowohl die Childhood Group der International Obesity Task Force (IOTF) als auch die European Childhood Obesity Group (ECOG) empfehlen den Body-mass-Index als Beurteilungskriterium für Übergewicht und Adipositas bei Kindern und Jugendlichen. Im Erwachsenenalter erfolgt die Definition von Übergewicht und Adipositas anhand fester Grenzwerte, bei der Beurteilung von Kindern und Jugendlichen müssen die alters- und geschlechtsspezifischen Veränderungen des BMI berücksichtigt werden. Methode: Unter Heranziehung von 17 bereits durchgeführten Untersuchungen aus verschiedenen Regionen Deutschlands wurden BMI-Perzentile für Kinder und Jugendliche erstellt. Die Berechnung der Perzentile basiert auf den Körperhöhen- und Körpergewichtsdaten von 17.147 Jungen und 17.275 Mädchen im Alter von 0–18 Jahren. Ergebnisse und Schlussfolgerung: Die vorgestellten Perzentile sollten als Referenz für deutsche Kinder und Jugendliche angewendet werden. Die Arbeitsgemeinschaft „Adipositas im Kindes- und Jugendalter“ (AGA) hat in ihren Leitlinien die Anwendung der hier vorgestellten 90. und 97. Perzentile zur Definition von Übergewicht und Adipositas empfohlen.Objectives: Both the Childhood Group of the International Obesity Task Force (IOTF) and the European Childhood Obesity Group (ECOG) recommend to use the body mass index (BMI = weight in kilograms/height in meter2) to evaluate overweight and obesity in children and adolescents. Whereas it is customary with adults to use fixed cut off points to define overweight and obesity, in children and adolescents age and sex specific developmental changes in BMI need to be addressed, which are due to physiological alterations of fat mass. Method: Because a national reference population for children and adolescents does not exist in Germany, a BMI reference data set was compiled. Therefore measurements of height and weight from 17 different regional studies including 17147 boys and 17275 girls aged 0 to 18 years were used. Results and conclusions: We recommend the use of the presented percentiles as reference to asses under- and overweight (obesity) in German children and adolescents. In the guidelines of the “Arbeitsgruppe Adipositas im Kindes- und Jugendalter”(AGA) the 90th and 97th BMI percentiles as calculated in this reference population are proposed as cut-off points for the definition of overweight and obesity in German children and adolescents

A Scoping Review of Home Produced Heroin and Amphetamine Type Stimulant Substitutes: Implications for Prevention, Treatment and Policy

Several home-produced substances such as krokodil and boltushka are prevalent in many Eastern European countries. Anecdotal reports of its use have been circulating in Germany and Norway; however, this has not been confirmed. Its use has also been reported by the media in the USA, although only one confirmed report of its use exists. Home-produced drugs are associated with high levels of morbidity and a number of complex health issues such as the spread of blood borne viruses, gangrene, and internal organ damage. The high incidence of HIV rates amongst people who inject home-produced substances is a public health concern. The resulting physical health consequences of injecting these crude substances are very severe in comparison to heroin or amphetamine acquired in black markets. Due to this fact and the increased mortality associated with these substances, professionals in the area of prevention, treatment, and policy development need to be cognisant of the presentation, harms, and the dangers associated with home-produced substances globally. This scoping review aimed to examine existing literature on the subject of home-produced heroin and amphetamine-type stimulant substitutes. The review discussed the many implications such research may have in the areas of policy and practice. Data were gathered through the use of qualitative secondary resources such as journal articles, reports, reviews, case studies, and media reports. The home production of these substances relies on the utilisation of precursor drugs such as less potent stimulants, tranquillizers, analgesics, and sedatives or natural plant ingredients. The Internet underpins the facilitation of this practice as recipes, and diverted pharmaceutical sales are available widely online, and currently, ease of access to the Internet is evident worldwide. This review highlights the necessity of prevention, education, and also harm reduction related to home-produced drugs and also recommends consistent monitoring of online drug fora, online drug marketplaces, and unregulated pharmacies