Mindfulness and the Need to Minimize the Risk of Harm: A Proposal to Implement and Enforce Standards for Secular Mindfulness Practice

While Western mindfulness practice is indeed beneficial for many participants, the research now clearly demonstrates that for some meditators, there are attendant potential risks. These potential risks to practitioners require a level of care from those individuals (and corporations) that disseminate mindfulness practice. Historically, in traditional Buddhist practice, mindfulness was but one of the eight factors on the Noble Eightfold Path. An important component of traditional practice strongly relies on ethics in the delivery of the practice. A formalized standard of care for modern, secular mindfulness practices, and a method to implement and enforce that standard, will greatly enhance safety and mitigate risks for both practitioners and teachers. Given the longstanding use of the “do no harm standard” in medicine, and the formalized governmental, regulatory, and licensure procedures applicable to medical and therapeutic practices, these fields offer the closest conventions upon which to base a proposed standard of care and a structure to implement and enforce standards for secular mindfulness practice and mindfulness-based interventions

Vertex Modeling of Confluent Cellular Networks Within a Molecular Dynamics Framework in LAMMPS

Cell migration is a fascinating biological phenomenon that plays a central role in vital bio-processes for organisms including, but not limited to, immune response, wound repair, and tissue homeostasis. Models of cell migration are also used to emulate harmful epithelial cancers and collective bacterial movement. Many computational models have been proposed about this topic, but they are often very complex to implement and therefore have cost and size limitations. The purpose of this project is to implement an active vertex model in a particle dynamics framework software, knownas the Large-Scale Atomic/Molecular Massively Parallel Simulator (LAMMPS). By applying the forces to cell centers instead of cell vertices, we can use particles to simulate cells and use a Dual Voronoi Tessellation to calculate the forces needed. Using LAMMPS allows us to take advantage of its highly parallel nature, providing a framework for larger and more complex systems. Our results include time-step convergence analysis, unjamming transition simulations, and modelled motion of an endothelial cell monolayer on a grooved substrate. Simulating these migratory patterns and understanding their biophysical significance has applications in a wide range of diverse domains including organoid development, stem cell research, and endovascular device design.</p

Characterization of bacterial lipooligosaccharides by delayed extraction matrix-assisted laser desorption ionization time-of-flight mass spectrometry

Matrix-assisted laser desorption ionization (MALDI) with a time-of-flight analyzer has been used to analyze bacterial lipooligosaccharides (LOS). Crude LOS preparations from pathogenic strains of Haemophilus influenzae and Haemophilus ducreyi and a commercial preparation of lipopolysaccharide from Salmonella typhimurium were treated with hydrazine to remove O-linked fatty acids on the lipid A moiety. The resulting O-deacylated LOS forms were water soluble and more amenable to cocrystallization with standard MALDI matrices such as 2,5-dihydroxybenzoic acid and 1-hydroxyisoquinoline. Under continuous extraction conditions, O-deacylated LOS yielded broad peaks with abundant salt adducts as well as forming prompt fragments through β-elimination of phosphoric acid, that is, [M-H3PO4-H]. However, when a time delay was used between ionization and extraction (“delayed extraction”) a significant improvement was seen in both mass resolution and the stability of the molecular ions against β-elimination of phosphoric acid, especially in the negative-ion mode. Both an external two-point calibration and an internal single-point calibration were used to assign masses, the latter of which provided the highest degree of accuracy (better than 0.01% in most cases). At higher laser powers, the LOS molecules cleave readily between the oligosaccharide and lipid A moieties yielding a number of prompt fragments. Postsource decay (PSD) analysis of selected molecular ions provided a set of fragments similar to those seen in the linear spectra, although they were more limited in number because they were derived from a single LOS-glycoform. Both the prompt and PSD fragments provided important structural information, especially in assigning the phosphate and phosphoethanolamine substitution pattern of the lipid A and oligosaccharide portions of LOS. Last, with the addition of ethylenediaminetetraacetic acid followed by pulsed sonication, the relatively insoluble (and impure) LOS preparations yielded MALDI spectra similar to the O-deacylated LOS, although these intact LOS preparations required higher laser powers to ionize and were generally more affected by competing impurities

M. tuberculosis Ser/Thr Protein Kinase D Phosphorylates an Anti-Anti–Sigma Factor Homolog

Receptor Ser/Thr protein kinases are candidates for sensors that govern developmental changes and disease processes of Mycobacterium tuberculosis (Mtb), but the functions of these kinases are not established. Here, we show that Mtb protein kinase (Pkn) D overexpression alters transcription of numerous bacterial genes, including Rv0516c, a putative anti-anti–sigma factor, and genes regulated by sigma factor F. The PknD kinase domain directly phosphorylated Rv0516c, but no other sigma factor regulator, in vitro. In contrast, the purified PknB and PknE kinase domains phosphorylated distinct sigma regulators. Rather than modifying a consensus site, PknD phosphorylated Rv0516c in vitro and in vivo on Thr2 in a unique N-terminal extension. This phosphorylation inhibited Rv0516c binding in vitro to a homologous anti-anti–sigma factor, Rv2638. These results support a model in which signals transmitted through PknD alter the transcriptional program of Mtb by stimulating phosphorylation of a sigma factor regulator at an unprecedented control site

Proteomics and electron microscopic characterization of the unusual mitochondrial ribosome-related 45S complex in Leishmania tarentolae

A novel type of ribonucleoprotein (RNP) complex has been described from the kinetoplast-mitochondria of Leishmania tarentolae. The complex, termed the 45S SSU*, contains the 9S small subunit rRNA but does not contain the 12S large subunit rRNA. This complex is the most stable and abundant mitochondrial RNP complex present in Leishmania. As shown by tandem mass spectrometry, the complex contains at least 39 polypeptides with a combined molecular mass of almost 2.1 MDa. These components include several homologs of small subunit ribosomal proteins (S5, S6, S8 S9, S11, S15, S16, S17, S18, MRPS29); however, most of the polypeptides present are unique. Only a few of them show recognizable motifs, such as protein-protein (coiled-coil, Rhodanese) or protein-RNA (pentatricopeptide repeat) interaction domains. A cryo-electron microscopy examination of the 45S SSU* fraction reveals that 27% of particles represent SSU homodimers arranged in a head-to-tail orientation, while the majority of particles are clearly different and show an asymmetric bilobed morphology. Multiple classes of two-dimensional averages were derived for the asymmetrical particles, probably reflecting random orientations of the particles and difficulties in correlating these views with the known projections of ribosomal complexes. One class of the two-dimensional averages shows an SSU moiety attached to a protein mass or masses in a monosome-like appearance. The combined mass spectrometry and electron microscopy data thus indicate that the majority 45S SSU* particles represents a heterodimeric complex in which the SSU of the Leishmania mitochondrial ribosome is associated with an additional protein mass. The biological role of these particles is not known

Identification and characterization by LC-UV-MS/MS of melanotan II skin-tanning products sold illegally on the Internet

New methods were developed and validated to determine the identity, contents, and purity of samples of melanotan II, asynthetic melanocortin receptor agonist, sold in vials as injectable skin-tanning products that were purchased from three online shops. Methods were based on liquid chromatography with ultra-violet detection (LC-UV) at wavelength 218 nm, and tandem mass spectrometric detection (MS/MS) after collision-induced fragmentation of the double charged [M+2H]²⁺precursor ion (m/z ²⁺513). Identification of melanotan II was verified by correct chromatographic retention time, and relative abundance ratios of five qualifying fragment ions. LC-UV was used to quantify melanotan II as well as impurities. Method validation was performed with reference to guidelines for assessing active substances in authorized medicinal products to reach acceptable accuracy and precision. Vials from two shops contained unknown impurities ranging from 4.1 to 5.9%; impurities from one shop were below the quantification limit. The total amount of melanotan II in vials ranged between 4.32 and 8.84 mg, although each shop claimed that vials contained 10 mg melanotan II. A broad range of drugs used for enhancement purposes can be obtained from the illicit market. However, users of these drugs may be exposed to a range of potential harms, as shown in this study, given that these products are manufactured, distributed and supplied from an illicit market

Histone Deacetylase Inhibitors Globally Enhance H3/H4 Tail Acetylation Without Affecting H3 Lysine 56 Acetylation

Histone deacetylase inhibitors (HDACi) represent a promising avenue for cancer therapy. We applied mass spectrometry (MS) to determine the impact of clinically relevant HDACi on global levels of histone acetylation. Intact histone profiling revealed that the HDACi SAHA and MS-275 globally increased histone H3 and H4 acetylation in both normal diploid fibroblasts and transformed human cells. Histone H3 lysine 56 acetylation (H3K56ac) recently elicited much interest and controversy due to its potential as a diagnostic and prognostic marker for a broad diversity of cancers. Using quantitative MS, we demonstrate that H3K56ac is much less abundant than previously reported in human cells. Unexpectedly, in contrast to H3/H4 N-terminal tail acetylation, H3K56ac did not increase in response to inhibitors of each class of HDACs. In addition, we demonstrate that antibodies raised against H3K56ac peptides cross-react against H3 N-terminal tail acetylation sites that carry sequence similarity to residues flanking H3K56

A systematic scoping review and textual narrative synthesis of long-term health-related quality of life outcomes for adolescent idiopathic scoliosis

Introduction Idiopathic scoliosis is a musculoskeletal condition leading to deformity of the spinal column. There is a strong evidence reporting short term health-related quality of life outcomes, but less is known about the longer-term impact of adolescent idiopathic scoliosis (AIS). This paper reports the current evidence on long-term non-clinical outcomes of AIS. Method A systematic scoping literature review, combining descriptive and textual narrative synthesis was undertaken. Studies were included if they sampled or followed up participants at least 10 years after diagnosis and / or treatment, contained health-related quality of life data that could be extracted, where the intervention (or diagnosis in the case of untreated) occurred after 1980 and where data was extractable for modern rod and screw or fusion techniques, non-surgical interventions or untreated patients. Results Twenty-three studies were included. Overall, the HRQOL measures utilised by these studies suggest that HRQOL is not related to participant demographic or AIS characteristics or type or extent of surgical intervention. Some studies suggest that those with AIS scored worse than controls. Discussion Results suggest that AIS participants had a generally good quality of life, although this was often worse than those without AIS. No other clear relationships were found. Importantly, the available literature fails to address more fundamental questions about how HRQOL is conceptualised for those with AIS, and there is value in pursuing qualitative inquiry in this area