Barriers and facilitators to becoming an alcohol and other drug nurse practitioner in Australia: A mixed methods study.

Alcohol and other drug (AOD) nurse practitioners have an advanced scope of practice that allows them to diagnose, prescribe pharmacological treatments for alcohol and other substance use disorders, and monitor physical and mental health. The Behaviour Change Wheel (BCW) is used to understand barriers and facilitators to implementation by applying three conditions of behaviour change (capability, opportunity, and motivation-the COM-B framework). The aim of this paper is to describe the current AOD nurse practitioner workforce, and to explore barriers and facilitators to AOD nurse practitioner uptake in Australia. A mixed method approach was used in this study: a survey to determine the current state of the AOD nurse practitioner workforce (n = 41) and qualitative interviews with 14 participants to determine barriers to endorsement and ongoing work as a nurse practitioner. Interview transcripts were analysed using thematic analysis and mapped to the COM-B framework. The AOD nurse practitioner is a highly specialized provider of holistic care to people who use alcohol and other drugs, with AOD nurse practitioners performing advanced roles such as prescribing and medication management. However, there are several barriers to the further uptake of AOD nurse practitioners in Australia, including varied organizational support, a lack of support for the higher study required to become a nurse practitioner and a lack of available positions. Arguably, nurse practitioners are key to addressing prescriber shortages inherent in AOD treatment settings. In addition, they are equipped to provide true holistic care. We recommend that barriers are addressed to expand the AOD nurse practitioner workforce in Australia.

Gram-negative Cranial Bone Flap Infection Treated with Continuous Gentamicin Irrigation: A Case Report.

A 57-year-old male presented with severely altered mental status in the setting of diabetic ketoacidosis. Neuroimaging revealed two intracranial masses. Days following surgical resection of an olfactory groove meningioma, the patient developed Serratia marcescens bacteremia along with an enlarging epidural and subgaleal fluid collection. Subgaleal fluid aspiration was also positive. The patient later returned to the operating room for wound washout where purulent collections were discovered in the subgaleal, epidural, and left subdural spaces. The wound was evacuated and the bone flap was thoroughly cleansed with betadine and soaked in peroxide prior to replacement. Four drains were placed (two subgaleal and two epidural) with two serving as inlets and two as outlets. Continuous irrigation of the subgaleal and epidural spaces with gentamicin solution was performed for five days. The bone flap was successfully salvaged and the patient was discharged from inpatient rehab three weeks following washout.

Mechanism of Rh2(II)-Catalyzed Indole Formation: The Catalyst Does Not Control Product Selectivity.

Possible mechanisms for Rh-promoted indole formation from vinyl/azidoarenes were examined computationally, and a mechanism is proposed in which the Rh catalyst promotes generation of a nitrene but is not directly involved in cyclization.

An unusual case of schwannomatosis with bilateral maxillary sinus schwannomas and a novel SMARCB1 gene mutation.

Schwannomas are benign tumors that arise from Schwann cells in the peripheral nervous system. Patients with multiple schwannomas without signs and symptoms of neurofibromatosis Type 1 or 2 have the rare disease schwannomatosis. Tumors in these patients occur along peripheral nerves throughout the body. Mutations of the SMARCB1 gene have been described as one of the predisposing genetic factors in the development of this disease. This report describes a patient who was observed for 6 years after having undergone removal of 7 schwannomas, including bilateral maxillary sinus schwannomas, a tumor that has not been previously reported. Genetic analysis revealed a novel mutation of c.93G>A in exon 1 of the SMARCB1 gene.

Multiple unilateral traumatic carotid-cavernous sphenoid sinus fistulas with associated massive epistaxis: a consequence of parkour.

BACKGROUND: Traumatic carotid-cavernous fistulas (CCFs) present the clinician with diagnostic and surgical challenges. Extension of a CCF into the sphenoid sinus presents additional management difficulties. Endovascular interventions using various thrombogenic materials such as balloons, coils, or liquids are effective treatment strategies. Ideally, these techniques are used to obliterate the fistula while maintaining the patency of the parent artery. CASE REPORT: We present a rare case of traumatic carotid-cavernous sphenoid sinus fistulas complicated by multiple tears in the internal carotid artery with direct communication to the cavernous and sphenoid sinus. As a result, the patient developed massive epistaxis requiring emergent endovascular intervention. A total of 87 detachable coils were placed into the cavernous and sphenoid sinuses via transarterial and transvenous routes in a staged procedure, resulting in complete obliteration of the patient's multiple fistulas. CONCLUSION: To our knowledge, this is the first reported case of multiple fistulous tears in the internal carotid artery with extension to the cavernous and sphenoid sinus. This report emphasizes the importance of early diagnosis and neurosurgical intervention.

Visually impaired researchers get their hands on quantum chemistry: application to a computational study on the isomerization of a sterol.

In molecular sciences, articles tend to revolve around 2D representations of 3D molecules, and sighted scientists often resort to 3D virtual reality software to study these molecules in detail. Blind and visually impaired (BVI) molecular scientists have access to a series of audio devices that can help them read the text in articles and work with computers. Reading articles published in this journal, though, is nearly impossible for them because they need to generate mental 3D images of molecules, but the article-reading software cannot do that for them. We have previously designed AsteriX, a web server that fully automatically decomposes articles, detects 2D plots of low molecular weight molecules, removes meta data and annotations from these plots, and converts them into 3D atomic coordinates. AsteriX-BVI goes one step further and converts the 3D representation into a 3D printable, haptic-enhanced format that includes Braille annotations. These Braille-annotated physical 3D models allow BVI scientists to generate a complete mental model of the molecule. AsteriX-BVI uses Molden to convert the meta data of quantum chemistry experiments into BVI friendly formats so that the entire line of scientific information that sighted people take for granted-from published articles, via printed results of computational chemistry experiments, to 3D models-is now available to BVI scientists too. The possibilities offered by AsteriX-BVI are illustrated by a project on the isomerization of a sterol, executed by the blind co-author of this article (HBW).

Short interfering RNA guide strand modifiers from computational screening.

Short interfering RNAs (siRNAs) are promising drug candidates for a wide range of targets including those previously considered "undruggable". However, properties associated with the native RNA structure limit drug development, and chemical modifications are necessary. Here we describe the structure-guided discovery of functional modifications for the guide strand 5'-end using computational screening with the high-resolution structure of human Ago2, the key nuclease on the RNA interference pathway. Our results indicate the guide strand 5'-end nucleotide need not engage in Watson-Crick (W/C) H-bonding but must fit the general shape of the 5'-end binding site in MID/PIWI domains of hAgo2 for efficient knockdown. 1,2,3-Triazol-4-yl bases formed from the CuAAC reaction of azides and 1-ethynylribose, which is readily incorporated into RNA via the phosphoramidite, perform well at the guide strand 5'-end. In contrast, purine derivatives with modified Hoogsteen faces or N2 substituents are poor choices for 5'-end modifications. Finally, we identified a 1,2,3-triazol-4-yl base incapable of W/C H-bonding that performs well at guide strand position 12, where base pairing to target was expected to be important. This work expands the repertoire of functional nucleotide analogues for siRNAs.

Computational approaches to predicting the impact of novel bases on RNA structure and stability.

The use of computational modeling techniques to gain insight into nucleobase interactions has been a challenging endeavor to date. Accurate treatment requires the tackling of many challenges but also holds the promise of great rewards. The development of effective computational approaches to predict the binding affinities of nucleobases and analogues can, for example, streamline the process of developing novel nucleobase modifications, which should facilitate the development of new RNAi-based therapeutics. This brief review focuses on available computational approaches to predicting base pairing affinity in RNA-based contexts such as nucleobase-nucleobase interactions in duplexes and nucleobase-protein interactions. The challenges associated with such modeling along with potential future directions for the field are highlighted.

Is Al2Cl6 aromatic? Cautions in superficial NICS interpretation.

In this article, we employed the induced magnetic field method to show that the Al2X6 (X = F, Cl, Br, I) clusters cannot be classified as aromatic systems. Interestingly, even nucleus independent chemical shift (NICS) reveals the same conclusion when analyzed in greater detail, showing that a superficial analysis of this index can easily lead to incorrect interpretations. In view of the fact that the NICS index is extensively used by computational and theoretically oriented experimental chemists, this is an important warning against superficial analyses, as it can lead to erroneous chemical interpretation.

A high-throughput and quantitative method to assess the mutagenic potential of translesion DNA synthesis.

Cellular genomes are constantly damaged by endogenous and exogenous agents that covalently and structurally modify DNA to produce DNA lesions. Although most lesions are mended by various DNA repair pathways in vivo, a significant number of damage sites persist during genomic replication. Our understanding of the mutagenic outcomes derived from these unrepaired DNA lesions has been hindered by the low throughput of existing sequencing methods. Therefore, we have developed a cost-effective high-throughput short oligonucleotide sequencing assay that uses next-generation DNA sequencing technology for the assessment of the mutagenic profiles of translesion DNA synthesis catalyzed by any error-prone DNA polymerase. The vast amount of sequencing data produced were aligned and quantified by using our novel software. As an example, the high-throughput short oligonucleotide sequencing assay was used to analyze the types and frequencies of mutations upstream, downstream and at a site-specifically placed cis-syn thymidine-thymidine dimer generated individually by three lesion-bypass human Y-family DNA polymerases.

Isomerization energy decomposition analysis for highly ionic systems: case study of starlike E5Li7(+) clusters.

The most stable forms of E(5)Li(7)(+) (E = Ge, Sn, and Pb) have been explored by means of a stochastic search of their potential-energy surfaces by using the gradient embedded genetic algorithm (GEGA). The preferred isomer of the Ge(5)Li(7)(+) ion is a slightly distorted analogue of the D(5h) three-dimensional seven-pointed starlike structure adopted by the lighter C(5)Li(7)(+) and Si(5)Li(7)(+) clusters. In contrast, the preferred structures for Sn(5)Li(7)(+) and Pb(5)Li(7)(+) are quite different. By starting from the starlike arrangement, corresponding lowest-energy structures are generated by migration of one of the E atoms out of the plane with the a corresponding rearrangement of the Li atoms. To understand these structural preferences, we propose a new energy decomposition analysis based on isomerizations (isomerization energy decomposition analysis (IEDA)), which enable us to extract energetic information from isomerization between structures, mainly from highly charged fragments.

Role of gold in a complex cascade reaction involving two electrocyclization steps.

Quantum chemical computations (B3LYP/LACVP**) were applied to assess the impact of Au(I) complexation on activation barriers for sequential electrocyclization reactions (one a 1,2-dihydroazete ring-opening and another a pentadienyl cation ring-closure) proposed to occur during a complex reaction cascade that converts alkynes and imines to cyclopentenimines.

Carbonium vs. carbenium ion-like transition state geometries for carbocation cyclization - how strain associated with bridging affects 5-exo vs. 6-endo selectivity.

Quantum chemical calculations are used to explore the origins of regioselectivity for proton-, Pt(II)- and Pd(II)-promoted cyclizations of 1,5-hexadienes, 5-aminoalkenes, and allylic acetimidates. The strain associated with achieving carbonium ion-like transition state geometries is shown to be a key factor in controlling 5-exo vs. 6-endo selectivity.

Acid and base catalyzed Davis-Beirut reaction: experimental and theoretical mechanistic studies and synthesis of novel 3-amino-2H-indazoles.

The Davis-Beirut reaction, which provides an efficient synthesis of 2H-indazoles and, subsequently, indazolones, is shown to proceed rapidly from o-nitrosobenzaldehyde and primary amines under both acid or base catalysis. Experimental and theoretical evidence in support of a reaction mechanism is provided in which o-nitrosobenzylidine imine is a pivotal intermediate in this N,N-bond forming heterocyclization reaction. The Davis-Beirut reaction is also shown to effectively synthesize a number of novel 3-amino-2H-indazole derivatives.

Re-examining the mechanisms of competing pericyclic reactions of 1,3,7-octatriene.

DFT (both B3LYP and M06-2X), CASSCF, and CASPT2 calculations were used to investigate competing [3, 3] and [3, 5] sigmatropic shifts and intramolecular [4+2] cycloaddition of 1,3,7-octatriene. In accord with previous results on 1,5-hexadiene, CASSCF calculations found both stepwise and concerted pathways for the [3, 3] rearrangement. For the competing [3, 5] sigmatropic rearrangement, CASSCF and CASPT2 calculations revealed three stepwise pathways with similar barriers. UB3LYP and UM06-2X calculations predicted a different potential energy landscape: no stepwise [3, 3] pathway, only two competing [3, 5] sigmatropic shifts, and an intramolecular Diels-Alder cycloaddition/homolytic ring-opening pathway. Significant lowering of barriers for all rearrangements was predicted for some 1,3,7-octatrienes with substituents at the 4- and 7-positions.

Fusing cubanes to 1,5-hexadiene.

Density functional theory calculations are used to predict structures and reactivity (barriers for sigmatropic shifts and retrocycloadditions) of 1,5-hexadienes fused to cubanes.

Fragmentation of oxime and silyl oxime ether odd-electron positive ions by the McLafferty rearrangement: new insights on structural factors that promote α,ß fragmentation.

The McLafferty rearrangement is an extensively studied fragmentation reaction for the odd-electron positive ions from a diverse range of functional groups and molecules. Here, we present experimental and theoretical results of 12 model compounds that were synthesized and investigated by GC-TOF MS and density functional theory calculations. These compounds consisted of three main groups: carbonyls, oximes and silyl oxime ethers. In all electron ionization mass spectra, the fragment ions that could be attributed to the occurrence of a McLafferty rearrangement were observed. For t-butyldimethylsilyl oxime ethers with oxygen in a ß-position, the McLafferty rearrangement was accompanied by loss of the t-butyl radical. The various mass spectra showed that the McLafferty rearrangement is relatively enhanced compared with other primary fragmentation reactions by the following factors: oxime versus carbonyl, oxygen versus methylene at the ß-position and ketone versus aldehyde. Calculations predict that the stepwise mechanism is favored over the concerted mechanism for all but one compound. For carbonyl compounds, C-C bond breaking was the rate-determining step. However, for both the oximes and t-butyldimethylsilyl oxime ethers with oxygen at the ß-position, the hydrogen transfer step was rate limiting, whereas with a CH(2) group at the ß-position, the C-C bond breaking was again rate determining. n-Propoxy-acetaldehyde, bearing an oxygen atom at the ß-position, is the only case that was predicted to proceed through a concerted mechanism. The synthesized oximes exist as both the (E)- and (Z)-isomers, and these were separable by GC. In the mass spectra of the two isomers, fragment ions that were generated by the McLafferty rearrangement were observed. Finally, fragment ions corresponding to the McLafferty reverse charge rearrangement were observed for all compounds at varying relative ion intensities compared with the conventional McLafferty rearrangement.

Small molecule signaling agents: the integrated chemistry and biochemistry of nitrogen oxides, oxides of carbon, dioxygen, hydrogen sulfide, and their derived species.

Several small molecule species formally known primarily as toxic gases have, over the past 20 years, been shown to be endogenously generated signaling molecules. The biological signaling associated with the small molecules NO, CO, H2S (and the nonendogenously generated O2), and their derived species have become a topic of extreme interest. It has become increasingly clear that these small molecule signaling agents form an integrated signaling web that affects/regulates numerous physiological processes. The chemical interactions between these species and each other or biological targets is an important factor in their roles as signaling agents. Thus, a fundamental understanding of the chemistry of these molecules is essential to understanding their biological/physiological utility. This review focuses on this chemistry and attempts to establish the chemical basis for their signaling functions.

Gliomatosis cerebri: report of 3 cases.

Gliomatosis cerebri is an uncommon glial neoplasm that is exceedingly rare in children and difficult to diagnose. The authors describe the presentation and diagnosis of GC in 3 children ages 12, 14, and 16 years. These children exhibited signs and symptoms of increased intracranial pressure as well as other vague or site specific neurological signs. Because clinical presentation, CSF analysis, and neuroimaging were nonspecific, a stereotactic biopsy to obtain tissue for pathological review was ultimately necessary to confirm the diagnosis. These pediatric cases underscore the limitations of relying solely on clinical presentation and neuroimaging and call to attention the essential role of neurosurgical intervention. The authors emphasize the need to maintain gliomatosis cerebri in the differential diagnosis of children presenting with diffuse neurological signs and MR imaging evidence of widespread, infiltrative lesions.