A case of rapid-onset daptomycin-induced neutropenia

A 75-year-old Caucasian woman was transferred to a tertiary academic medical center for management of a foul smelling, non-draining, unstageable sacral pressure ulcer. Upon admission, the patient's laboratory data was notable for a white blood cell count (WBC) of 14.90 x 10-3/[mu]L and absolute neutrophil count of 12.24 x 10-3 /[mu]L. After a complicated hospital course the patient was initiated on daptomycin 6 mg/kg (300 mg) daily in response to wound cultures detecting Enterococcus faecium susceptible only to daptomycin and linezolid. Starting 96 hours after daptomycin initiation, there was a profound reduction in the patient's WBC, reaching a nadir of 1.63 x 10-3 /[mu]L after 12 days of therapy. Prior to documented resolution of her blood dyscrasia the patient was transferred to hospice care and use of antimicrobial therapy was withdrawn. The Naranjo Adverse Drug Reaction Probability Score demonstrated a probable relationship (score equal to 6) between daptomycin and the development of neutropenia. Unlike previous reports of daptomycin-induced neutropenia and/or thrombocytopenia, where patients received prolonged courses of daptomycin with doses ranging from 6-10 mg/kg, this case describes a much more rapid onset of neutropenia that occurred at a dose of 6 mg/kg/day. This case reports highlights the risk for daptomycin to induce neutropenia in patients receiving traditional dosing, not just at higher doses, and within a shorter time-frame than previously documented. Healthcare providers should be cognizant of this adverse reaction, and diligent in monitoring for adverse events, associated with daptomycin use even when used for short courses or at traditional doses

Exploiting online social gambling for marketing communications

Internet technology provides a new approach to how gambling is conducted in postmodern times. Drawing on constructivist research and utilising a single case study strategy, this paper examines online social gambling and real money gambling marketing communication practices, as well as offering some insights into the development and implementation of effective marketing communication programmes. In contrast to existing studies, this paper, in part, proposes integrative and higher levels of marketing communication programmes between online social gambling and real money gambling environments. The paper reveals the implicit structure of meanings underlying the link between online social gambling activity and real money gambling practices

De novo formation of an aggregation pheromone precursor by an isoprenyl diphosphate synthase-related terpene synthase in the harlequin bug.

Insects use a diverse array of specialized terpene metabolites as pheromones in intraspecific interactions. In contrast to plants and microbes, which employ enzymes called terpene synthases (TPSs) to synthesize terpene metabolites, limited information from few species is available about the enzymatic mechanisms underlying terpene pheromone biosynthesis in insects. Several stink bugs (Hemiptera: Pentatomidae), among them severe agricultural pests, release 15-carbon sesquiterpenes with a bisabolene skeleton as sex or aggregation pheromones. The harlequin bug, Murgantia histrionica, a specialist pest of crucifers, uses two stereoisomers of 10,11-epoxy-1-bisabolen-3-ol as a male-released aggregation pheromone called murgantiol. We show that MhTPS (MhIDS-1), an enzyme unrelated to plant and microbial TPSs but with similarity to trans-isoprenyl diphosphate synthases (IDS) of the core terpene biosynthetic pathway, catalyzes the formation of (1S,6S,7R)-1,10-bisaboladien-1-ol (sesquipiperitol) as a terpene intermediate in murgantiol biosynthesis. Sesquipiperitol, a so-far-unknown compound in animals, also occurs in plants, indicating convergent evolution in the biosynthesis of this sesquiterpene. RNAi-mediated knockdown of MhTPS mRNA confirmed the role of MhTPS in murgantiol biosynthesis. MhTPS expression is highly specific to tissues lining the cuticle of the abdominal sternites of mature males. Phylogenetic analysis suggests that MhTPS is derived from a trans-IDS progenitor and diverged from bona fide trans-IDS proteins including MhIDS-2, which functions as an (E,E)-farnesyl diphosphate (FPP) synthase. Structure-guided mutagenesis revealed several residues critical to MhTPS and MhFPPS activity. The emergence of an IDS-like protein with TPS activity in M. histrionica demonstrates that de novo terpene biosynthesis evolved in the Hemiptera in an adaptation for intraspecific communication

Perceptions of extended-release buprenorphine injections for opioid use disorder among people who regularly use opioids in Australia

2019 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction Aims: To examine perceptions of extended-release (XR) buprenorphine injections among people who regularly use opioids in Australia. Design: Cross-sectional survey prior to implementation. XR-buprenorphine was registered in Australia in November 2018. Setting: Sydney, Melbourne and Hobart. Participants. A total of 402 people who regularly use opioids interviewed December 2017 to March 2018. Measurements: Primary outcome concerned the proportion of participants who believed XR-buprenorphine would be a good treatment option for them, preferred weekly versus monthly injections and perceived advantages/disadvantages of XR-buprenorphine. Independent variables concerned the demographic characteristics and features of current opioid agonist treatment (OAT; medication-type, dose, prescriber/dosing setting, unsupervised doses, out-of-pocket expenses and travel distance). Findings: Sixty-eight per cent [95% confidence interval (CI) = 63-73%] believed XR-buprenorphine was a good treatment option for them. They were more likely to report being younger [26-35 versus \u3e 55 years; odds ratio (OR) = 3.16, 95% CI = 1.12-8.89; P = 0.029], being female (OR = 1.67, 95% CI = 1.04-2.69; P = 0.034), \u3c 10 years school education (OR = 1.87, 95% CI = 1.12-3.12; P = 0.016) and past-month heroin (OR = 1.81, 95% CI = 1.15-2.85; P = 0.006) and methamphetamine use (OR = 1.90, 95% CI = 1.20-3.01; P = 0.006). Fifty-four per cent reported no preference for weekly versus monthly injections, 7% preferred weekly and 39% preferred monthly. Among OAT recipients (n = 255), believing XR-buprenorphine was a good treatment option was associated with shorter treatment episodes (1-2 versus ≥ 2 years; OR = 3.93, 95% CI = 1.26-12.22; P = 0.018), fewer unsupervised doses (≤ 8 doses past-month versus no take-aways; OR = 0.50; 95% CI = 0.27-0.93; P = 0.028) and longer travel distance (≥ 5 versus \u3c 5 km; OR = 2.10, 95% CI = 1.20-3.65; P = 0.009). Sixty-nine per cent reported \u27no problems or concerns\u27 with potential differences in availability, flexibility and location of XR-buprenorphine. Conclusions: Among regular opioid users in Australia, perceptions of extended-release buprenorphine as a good treatment option are associated with being female, recent illicit drug use and factors relating to the (in)convenience of current opioid agonist treatment

Chalcogen Impact on Covalency within Molecular [Cu\u3csub\u3e3\u3c/sub\u3e(μ\u3csub\u3e3\u3c/sub\u3e-E)]\u3csup\u3e3+\u3c/sup\u3e Clusters (E = O, S, Se): A Synthetic, Spectroscopic, and Computational Study

Reaction of the tricopper(I)-dinitrogen tris(β-diketiminate) cyclophane, Cu3(N2)L, with O-atom-transfer reagents or elemental Se affords the oxido-bridged tricopper complex Cu3(μ3-O)L (2) or the corresponding Cu3(μ3-Se)L (4), respectively. For 2 and 4, incorporation of the bridging chalcogen donor was supported by electrospray ionization mass spectrometry and K-edge X-ray absorption spectroscopy (XAS) data. Cu L2,3-edge X-ray absorption data quantify 49.5% Cu 3d character in the lowest unoccupied molecular orbital of 2, with Cu 3d participation decreasing to 33.0% in 4 and 40.8% in the related sulfide cluster Cu3(μ3-S)L (3). Multiedge XAS and UV/visible/near-IR spectra are employed to benchmark density functional theory calculations, which describe the copper-chalcogen interactions as highly covalent across the series of [Cu3(μ-E)]3+ clusters. This result highlights that the metal-ligand covalency is not reserved for more formally oxidized metal centers (i.e., CuIII + O2- vs CuII + O-) but rather is a significant contributor even at more typical ligand-field cases (i.e., Cu3II/II/I + E2-). This bonding is reminiscent of that observed in p-block elements rather than in early-transition-metal complexes

Reduction of CO\u3csub\u3e2\u3c/sub\u3e By a Masked Two-Coordinate Cobalt(I) Complex and Characterization of a Proposed Oxodicobalt(II) Intermediate

Fixation and chemical reduction of CO2 are important for utilization of this abundant resource, and understanding the detailed mechanism of C-O cleavage is needed for rational development of CO2 reduction methods. Here, we describe a detailed analysis of the mechanism of the reaction of a masked two-coordinate cobalt(i) complex, LtBuCo (where LtBu = 2,2,6,6-tetramethyl-3,5-bis[(2,6-diisopropylphenyl)imino]hept-4-yl), with CO2, which yields two products of C-O cleavage, the cobalt(i) monocarbonyl complex LtBuCo(CO) and the dicobalt(ii) carbonate complex (LtBuCo)2(μ-CO3). Kinetic studies and computations show that the κN,η6-arene isomer of LtBuCo rearranges to the κ2N,N′ binding mode prior to binding of CO2, which contrasts with the mechanism of binding of other substrates to LtBuCo. Density functional theory (DFT) studies show that the only low-energy pathways for cleavage of CO2 proceed through bimetallic mechanisms, and DFT and highly correlated domain-based local pair natural orbital coupled cluster (DLPNO-CCSD(T)) calculations reveal the cooperative effects of the two metal centers during facile C-O bond rupture. A plausible intermediate in the reaction of CO2 with LtBuCo is the oxodicobalt(II) complex LtBuCoOCoLtBu, which has been independently synthesized through the reaction of LtBuCo with N2O. The rapid reaction of LtBuCoOCoLtBu with CO2 to form the carbonate product indicates that the oxo species is kinetically competent to be an intermediate during CO2 cleavage by LtBuCo. LtBuCoOCoLtBu is a novel example of a thoroughly characterized molecular cobalt-oxo complex where the cobalt ions are clearly in the +2 oxidation state. Its nucleophilic reactivity is a consequence of high charge localization on the μ-oxo ligand between two antiferromagnetically coupled high-spin cobalt(ii) centers, as characterized by DFT and multireference complete active space self-consistent field (CASSCF) calculations

Dual Action of lysophosphatidate- functionalised titanium: Interactions with human (MG63) osteoblasts and methicillin resistant staphylococcus aureus

© 2015 Skindersoe et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Titanium (Ti) is a widely used material for surgical implants; total joint replacements (TJRs), screws and plates for fixing bones and dental implants are forged from Ti. Whilst Ti integrates well into host tissue approximately 10% of TJRs will fail in the lifetime of the patient through a process known as aseptic loosening. These failures necessitate revision arthroplasties which are more complicated and costly than the initial procedure. Finding ways of enhancing early (osseo)integration of TJRs is therefore highly desirable and continues to represent a research priority in current biomaterial design. One way of realising improvements in implant quality is to coat the Ti surface with small biological agents known to support human osteoblast formation and maturation at Ti surfaces. Lysophosphatidic acid (LPA) and certain LPA analogues offer potential solutions as Ti coatings in reducing aseptic loosening. Herein we present evidence for the successful bio-functionalisation of Ti using LPA. This modified Ti surface heightened the maturation of human osteoblasts, as supported by increased expression of alkaline phosphatase. These functionalised surfaces also deterred the attachment and growth of Staphylococcus aureus, a bacterium often associated with implant failures through sepsis. Collectively we provide evidence for the fabrication of a dual-action Ti surface finish, a highly desirable feature towards the development of next-generation implantable devices

The silver bullet that wasn’t: Rapid agronomic weed adaptations to glyphosate in North America

The rapid adoption of glyphosate-resistant crops at the end of the 20th century caused a simplification of weed management that relied heavily on glyphosate for weed control. However, the effectiveness of glyphosate has diminished. A greater understanding of trends related to glyphosate use will shed new light on weed adaptation to a product that transformed global agriculture. Objectives were to (1) quantify the change in weed control efficacy from postemergence (POST) glyphosate use on troublesome weeds in corn and soybean and (2) determine the extent to which glyphosate preceded by a preemergence (PRE) improved the efficacy and consistency of weed control compared to glyphosate alone. Herbicide evaluation trials from 24 institutions across the United States of America and Canada from 1996 to 2021 were compiled into a single database. Two subsets were created; one with glyphosate applied POST, and the other with a PRE herbicide followed by glyphosate applied POST. Within each subset, mean and variance of control ratings for seven problem weed species were regressed over time for nine US states and one Canadian province. Mean control with POST glyphosate alone decreased over time while variability in control increased. Glyphosate preceded by a labeled PRE herbicide showed little change in mean control or variability in control over time. These results illustrate the rapid adaptation of agronomically important weed species to the paradigm-shifting product glyphosate. Including more diversity in weed management systems is essential to slowing weed adaptation and prolonging the usefulness of existing and future technologies

The Brain Atlas Concordance Problem: Quantitative Comparison of Anatomical Parcellations

Many neuroscientific reports reference discrete macro-anatomical regions of the brain which were delineated according to a brain atlas or parcellation protocol. Currently, however, no widely accepted standards exist for partitioning the cortex and subcortical structures, or for assigning labels to the resulting regions, and many procedures are being actively used. Previous attempts to reconcile neuroanatomical nomenclatures have been largely qualitative, focusing on the development of thesauri or simple semantic mappings between terms. Here we take a fundamentally different approach, discounting the names of regions and instead comparing their definitions as spatial entities in an effort to provide more precise quantitative mappings between anatomical entities as defined by different atlases. We develop an analytical framework for studying this brain atlas concordance problem, and apply these methods in a comparison of eight diverse labeling methods used by the neuroimaging community. These analyses result in conditional probabilities that enable mapping between regions across atlases, which also form the input to graph-based methods for extracting higher-order relationships between sets of regions and to procedures for assessing the global similarity between different parcellations of the same brain. At a global scale, the overall results demonstrate a considerable lack of concordance between available parcellation schemes, falling within chance levels for some atlas pairs. At a finer level, this study reveals spatial relationships between sets of defined regions that are not obviously apparent; these are of high potential interest to researchers faced with the challenge of comparing results that were based on these different anatomical models, particularly when coordinate-based data are not available. The complexity of the spatial overlap patterns revealed points to problems for attempts to reconcile anatomical parcellations and nomenclatures using strictly qualitative and/or categorical methods. Detailed results from this study are made available via an interactive web site at http://obart.info