Investigating practice integration of independent prescribing by community pharmacists using normalization process theory: a cross-sectional survey.

Independent prescribing (IP) has not been extensively investigated in community pharmacy (CP). Normalization Process Theory (NPT) constructs help explain how interventions are integrated into practice and include: 'coherence' (understanding), 'cognitive participation' (what promotes engagement), 'collective action' (integration with existing systems), 'reflexive monitoring (evaluation). The aim of this study was to use NPT to investigate the integration of pharmacist IP in CP. NHS Scotland Pharmacy First Plus (PFP) is a community pharmacy IP service. Questionnaire items were developed using the NPT derived Normalisation MeAsure Development (NoMAD) tool for an online survey of all PFP IP pharmacists. Demographic data were analysed descriptively and scale scores (calculated from item scores for the 4 NPT constructs) were used for inferential analysis. There was a 73% (88/120) response rate. Greater than 90% 'strongly agreed' / 'agreed' to NoMAD items relating to most NPT constructs. However, responses to 'collective action' items were diverse with more participants answering 'neither agree nor disagree' or 'disagree'. A statistically significant difference in NPT construct scale scores with significant p-values (ranging from p<0.001 to p=0.033) was shown on all the NPT constructs for the variable 'On average, how often do you consult with patients under the PFP service?'. This theory-based work offers perspectives on IP integration within CP. Despite its geographic focus this work offers insights relevant to wider contexts on IP integration. It shows 'collective action' focused 'organisation' and 'group process' challenges with a need for further work on staff training, resource availability and utilisation, working relationships, communication and management

Access to medicines in remote and rural areas: a survey of residents in the Scottish Highlands and Western Isles.

Objectives: Sparsely populated areas are potentially predisposed to health inequalities due to limited access to services. This study aimed to explore and describe issues of access to medicines and related advice experienced by residents of the Scottish Highlands and Western Isles. Study design: Cross-sectional cohort study. Methods: Anonymized questionnaires were mailed to a random sample of 6000 residents aged ≥18 years identified from the electoral register. The questionnaire contained items on: access to medicines; interactions with health care services; and perceptions of the services. Results were analysed using descriptive, inferential and spatial statistics. Results: Adjusted response rate was 49.5% (2913/5889). Almost two thirds (63.4%, 1847) were prescribed medicines regularly, 88.5% (1634) of whom considered the source convenient. Pharmacy (73.8%, 1364) or dispensing GP (24.0%, 443) were the most accessed sources. Prescription medicine advice was mainly obtained from the GP (55.7%, 1029). Respondents ≥80 years old were significantly (P0.0001) more likely to live alone (45.3%, 92) compared with those 80 (15.8%, 424). Almost a fifth (16.5%, 31) of those 80 years living alone disagreed that they obtained prescribed medicines from a convenient source. The majority of respondents who felt they did not have a convenient medicines source, regardless of urban/rural classification, lived within five miles of a pharmacy or GP practice. Conclusions: Respondents accessed medicines and advice from a variety of sources. While most considered their access to medicines convenient, there were issues for those over 80 years and living alone. Perceived convenience would not appear to be solely based on geographical proximity to supply source. This requires further exploration given that these individuals are likely to have long-term conditions and be prescribed medicines on a chronic basis

Computational redesign of acyl-ACP thioesterase with improved selectivity towards medium chain fatty acids at high production levels

Enzyme and metabolic engineering offer the potential to develop biocatalysts for converting natural resources into a wide range of chemicals. To broaden the scope of potential products beyond natural metabolites, methods of engineering enzymes to accept alternative substrates and/or perform novel chemistries must be developed. DNA synthesis can create large libraries of enzyme-coding sequences, but most biochemistries lack a simple assay to screen for promising enzyme variants. Our solution to this challenge is structure-guided mutagenesis in which optimization algorithms select the best sequences from libraries based on specified criteria (i.e. binding selectivity). Our computational procedure was demonstrated by tuning substrate binding of the highly-active ‘TesA thioesterase in Escherichia coli in favor of medium-chain (C6-C12) lengths. Specifically, the Iterative Protein Redesign & Optimization procedure (IPRO) was used to design ‘TesA variants with enhanced C12- or C8specificity while maintaining high activity. After four rounds of structure-guided mutagenesis, we identified three thioesterases with enhanced production of dodecanoic acid (C12) and twenty-seven thioesterases with enhanced production of octanoic acid (C8), the fatty acid products of thioesterase-mediated catalysis. The top variants reached up to 49% C12 and 50% C8 while exceeding native levels of total free fatty acids. A similar sized library created through random mutagenesis failed to identify medium-chain specific, highly-active variants. The chain length-preference of ‘TesA and the best mutant were confirmed in vitro using acyl-CoA substrates. Molecular dynamics simulations, confirmed by resolved crystal structures, of ‘TesA variants suggest that hydrophobic forces govern ‘TesA substrate specificity. In this work, we not only successfully modified ‘TesA substrate preference but in doing so, we identified the third most C12-specific and tenth most C8-specific thioesterase characterized to date. These results are significant because medium-chain fatty acids are limited in natural abundance relative to long-chain fatty acids. This limited supply leads to high costs of C6-C10 oleochemicals such as fatty alcohols, amines, and esters. We expect that the new thioesterase variants will be useful to metabolic engineering projects aimed at sustainable production of medium-chain oleochemicals. Furthermore, we anticipate that the lessons learned from both successful and failed computational designs can guide algorithmic advancements aiding with future enzyme engineering endeavors

Анализ возможности увеличения отпуска теплоты от Райчихинской ГРЭС

В процессе исследования проводились: оценка влияния теплофикации на производство электрической энергии; анализ текущего состояния и перспектив рынков электрической и тепловой энергий Амурской области, состояния оборудования Райчихинской ГРЭС и режимов работы станции; выбор температурного графика теплосети; определение варианта реконструкции турбоагрегата и теплофикационной установки; расчет экономической части проекта В результате исследования представлен и экономически обоснован вариант реконструкции Райчихинской ГРЭСThe study carried out: assessment of the impact of district heating for the production of electrical energy; analysis of the current state and prospects of the markets of electricity and thermal energy of the Amur region, state Raychihinsk TPP equipment and modes of operation of the station; choice of heating system temperature schedule; Certain embodiments of the reconstruction of the turbine unit and the heating unit; calculation of the economic part of the project The study is presented and economically feasible option for Reconstruction Raychihinsk GRE

Commercial vegetable weed, insect, and disease control guide: beets, carrots, lettuce, onions, parsnips, radishes, rutabagas, turnips, spinach (Revised 1990)

1 online resource (PDF, 12 pages)This archival publication may not reflect current scientific knowledge or recommendations. Current information available from the University of Minnesota Extension: https://www.extension.umn.edu

Application of BRET to monitor ligand binding to GPCRs

Bioluminescence resonance energy transfer (BRET) is a well-established method for investigating protein-protein interactions. Here we present a BRET approach to monitor ligand binding to G protein–coupled receptors (GPCRs) on the surface of living cells made possible by the use of fluorescent ligands in combination with a bioluminescent protein (NanoLuc) that can be readily expressed on the N terminus of GPCRs

Synthetic RNA modules for fine-tuning gene expression levels in yeast by modulating RNase III activity

The design of synthetic gene networks requires an extensive genetic toolbox to control the activities and levels of protein components to achieve desired cellular functions. Recently, a novel class of RNA-based control modules, which act through post-transcriptional processing of transcripts by directed RNase III (Rnt1p) cleavage, were shown to provide predictable control over gene expression and unique properties for manipulating biological networks. Here, we increase the regulatory range of the Rnt1p control elements, by modifying a critical region for enzyme binding to its hairpin substrates, the binding stability box (BSB). We used a high throughput, cell-based selection strategy to screen a BSB library for sequences that exhibit low fluorescence and thus high Rnt1p processing efficiencies. Sixteen unique BSBs were identified that cover a range of protein expression levels, due to the ability of the sequences to affect the hairpin cleavage rate and to form active cleavable complexes with Rnt1p. We further demonstrated that the activity of synthetic Rnt1p hairpins can be rationally programmed by combining the synthetic BSBs with a set of sequences located within a different region of the hairpin that directly modulate cleavage rates, providing a modular assembly strategy for this class of RNA-based control elements