The Antioxidant Potential of the Mediterranean Diet in Patients at High Cardiovascular Risk: An In-Depth Review of the PREDIMED

Cardiovascular disease (CVD) is the leading global cause of death. Diet is known to be important in the prevention of CVD. The PREDIMED trial tested a relatively low-fat diet versus a high-fat Mediterranean diet (MedDiet) for the primary prevention of CVD. The resulting reduction of the CV composite outcome resulted in a paradigm shift in CV nutrition. Though many dietary factors likely contributed to this effect, this review focuses on the influence of the MedDiet on endogenous antioxidant systems and the effect of dietary polyphenols. Subgroup analysis of the PREDIMED trial revealed increased endogenous antioxidant and decreased pro-oxidant activity in the MedDiet groups. Moreover, higher polyphenol intake was associated with lower incidence of the primary outcome, overall mortality, blood pressure, inflammatory biomarkers, onset of new-onset type 2 diabetes mellitus (T2DM), and obesity. This suggests that polyphenols likely contributed to the lower incidence of the primary event in the MedDiet groups. In this article, we summarize the potential benefits of polyphenols found in the MedDiet, specifically the PREDIMED cohort. We also discuss the need for further research to confirm and expand the findings of the PREDIMED in a non-Mediterranean population and to determine the exact mechanisms of action of polyphenols

Interactions of Cathinone NPS with Human Transporters and Receptors in Transfected Cells

Pharmacological assays carried out in transfected cells have been very useful for describing the mechanism of action of cathinone new psychoactive substances (NPS). These in vitro characterizations provide fast and reliable information on psychoactive substances soon after they emerge for recreational use. Well-investigated comparator compounds, such as methamphetamine, 3,4-methylenedioxymethamphetamine, cocaine, and lysergic acid diethylamide, should always be included in the characterization to enhance the translation of the in vitro data into clinically useful information. We classified cathinone NPS according to their pharmacology at monoamine transporters and receptors. Cathinone NPS are monoamine uptake inhibitors and most induce transporter-mediated monoamine efflux with weak to no activity at pre- or postsynaptic receptors. Cathinones with a nitrogen-containing pyrrolidine ring emerged as NPS that are extremely potent transporter inhibitors but not monoamine releasers. Cathinones exhibit clinically relevant differences in relative potencies at serotonin vs. dopamine transporters. Additionally, cathinone NPS have more dopaminergic vs. serotonergic properties compared with their non-β-keto amphetamine analogs, suggesting more stimulant and reinforcing properties. In conclusion, in vitro pharmacological assays in heterologous expression systems help to predict the psychoactive and toxicological effects of NPS

High Efficiency Colloidal Quantum Dot Infrared Light Emitting Diodes via Engineering at the Supra-Nanocrystalline Level

Colloidal quantum dot (CQD) light-emitting diodes (LEDs) deliver a compelling performance in the visible, yet infrared CQD LEDs underperform their visible-emitting counterparts, largely due to their low photoluminescence quantum efficiency. Here we employ a ternary blend of CQD thin film that comprises a binary host matrix that serves to electronically passivate as well as to cater for an efficient and balanced carrier supply to the emitting quantum dot species. In doing so, we report infrared PbS CQD LEDs with an external quantum efficiency of ~7.9% and a power conversion efficiency of ~9.3%, thanks to their very low density of trap states, on the order of 1014 cm−3, and very high photoluminescence quantum efficiency in electrically conductive quantum dot solids of more than 60%. When these blend devices operate as solar cells they deliver an open circuit voltage that approaches their radiative limit thanks to the synergistic effect of the reduced trap-state density and the density of state modification in the nanocomposite.Peer ReviewedPostprint (author's final draft

How did a Quality Premium financial incentive influence antibiotic prescribing in primary care? Views of Clinical Commissioning Group and general practice professionals

Background: The Quality Premium (QP) was introduced for Clinical Commissioning Groups (CCGs) in England to optimize antibiotic prescribing, but it remains unclear how it was implemented. Objectives: To understand responses to the QP and how it was perceived to influence antibiotic prescribing. Methods: Semi-structured telephone interviews were conducted with 22 CCG and 19 general practice professionals. Interviews were analysed thematically. Results: The findings were organized into four categories. (i) Communication: this was perceived as unstructured and infrequent, and CCG professionals were unsure whether they received QP funding. (ii) Implementation: this was influenced by available local resources and competing priorities, with multifaceted and tailored strategies seen as most helpful for engaging general practices. Many antimicrobial stewardship (AMS) strategies were implemented independently from the QP, motivated by quality improvement. (iii) Mechanisms: the QP raised the priority of AMS nationally and locally, and provided prescribing targets to aim for and benchmark against, but money was not seen as reinvested into AMS. (iv) Impact and sustainability: the QP was perceived as successful, but targets were considered challenging for a minority of CCGs and practices due to contextual factors (e.g. deprivation, understaffing). CCG professionals were concerned with potential discontinuation of the QP and prescribing rates levelling off. Conclusions: CCG and practice professionals expressed positive views of the QP and associated prescribing targets and feedback. The QP helped influence change mainly by raising the priority of AMS and defining change targets rather than providing additional funding. To maximize impact, behavioural mechanisms of financial incentives should be considered pre-implementation

Information Organization and Access in Digital Humanities: TaDiRAH Revised, Formalized and FAIR

Classifying and categorizing the activities that comprise the digital humanities (DH) has been a longstanding area of interest for many practitioners in this field, fueled by ongoing attempts to define the field both within the academic and public sphere. Several European initiatives are currently shaping advanced research infrastructures that would benefit from an implementation of a suiting taxonomy. Therefore, new humanities and information science collaborations have been formed to provide a service that meets their needs. This working paper presents the transformation of the Taxonomy of Digital Research Activities in the Humanities (TaDiRAH) in order to make it machine-readable and become a formalized taxonomy. This includes the methodology and realization containing a complete revision of the original version, decisions in modelling, the implementation as well as organization of ongoing and future tasks. TaDiRAH addresses a wide range of humanities disciplines and integrates application areas from philologies as well as epigraphy, and musicology to name just a few. For this reason, the decision in favor of SKOS was made purely pragmatically in terms of technology, concept and domains. New language versions can now be easily integrated and low-threshold term extensions can be carried out via Wikidata. The new TaDiRAH not only represents a knowledge organization system ( KOS ) which has recently been released as version 2.0. According to the FAIR principles this new version improves the Findability, Accessibility, Interoperability, and Reuse of research data and digital assets in the digital humanities

How can national antimicrobial stewardship interventions in primary care be improved? A stakeholder consultation

Many antimicrobial stewardship (AMS) interventions have been implemented in England, facilitating decreases in antibiotic prescribing. Nevertheless, there is substantial variation in antibiotic prescribing across England and some healthcare organizations remain high prescribers of antibiotics. This study aimed to identify ways to improve AMS interventions to further optimize antibiotic prescribing in primary care in England. Stakeholders representing different primary care settings were invited to, and 15 participated in, a focus group or telephone interview to identify ways to improve existing AMS interventions. Forty-five intervention suggestions were generated and 31 were prioritized for inclusion in an online survey. Fifteen stakeholders completed the survey appraising each proposed intervention using the pre-defined APEASE (i.e., Affordability, Practicability, Effectiveness, Acceptability, Safety, and Equity) criteria. The highest-rated nine interventions were prioritized as most promising and feasible, including: quality improvement, multidisciplinary peer learning, appointing AMS leads, auditing individual-level prescribing, developing tools for prescribing audits, improving inductions for new prescribers, ensuring consistent local approaches to antibiotic prescribing, providing online AMS training to all patient-facing staff, and increasing staff time available for AMS work with standardizing AMS-related roles. These prioritized interventions could be incorporated into existing national interventions or developed as stand-alone interventions to help further optimize antibiotic prescribing in primary care in England

Enzymatic Activities of Isolated Cytochrome bc1-like Complexes Containing Fused Cytochrome b Subunits with Asymmetrically Inactivated Segments of Electron Transfer Chains

Homodimeric structure of cytochrome bc_1, a common component of biological energy conversion systems, builds in four catalytic quinone oxidation/reduction sites and four chains of cofactors (branches) that, connected by a centrally located bridge, form a symmetric H-shaped electron transfer system. The mechanism of operation of this complex system is under constant debate. Here, we report on isolation and enzymatic examination of cytochrome bc1-like complexes containing fused cytochrome b subunits in which asymmetrically introduced mutations inactivated individual branches in various combinations. The structural asymmetry of those forms was confirmed spectroscopically. All the asymmetric forms corresponding to cytochrome bc_1 with partial or full inactivation of one monomer retain high enzymatic activity but at the same time show a decrease in the maximum turnover rate by a factor close to 2. This strongly supports the model assuming independent operation of monomers. The cross-inactivated form corresponding to cytochrome bc_1 with disabled complementary parts of each monomer retains the enzymatic activity at the level that, for the first time on isolated from membranes and purified to homogeneity preparations, demonstrates that intermonomer electron transfer through the bridge effectively sustains the enzymatic turnover. The results fully support the concept that electrons freely distribute between the four catalytic sites of a dimer and that any path connecting the catalytic sites on the opposite sides of the membrane is enzymatically competent. The possibility to examine enzymatic properties of isolated forms of asymmetric complexes constructed using the cytochrome b fusion system extends the array of tools available for investigating the engineering of dimeric cytochrome bc1 from the mechanistic and physiological perspectives

Optimising antimicrobial stewardship interventions in English primary care: a behavioural analysis of qualitative and intervention studies

Objective: While various interventions have helped reduce antibiotic prescribing, further gains can be made. This study aimed to identify ways to optimise antimicrobial stewardship (AMS) interventions by assessing the extent to which important influences on antibiotic prescribing are addressed (or not) by behavioural content of AMS interventions. Settings: English primary care. Interventions: AMS interventions targeting healthcare professionals’ antibiotic prescribing for respiratory tract infections. Methods: We conducted two rapid reviews. The first included qualitative studies with healthcare professionals on self-reported influences on antibiotic prescribing. The influences were inductively coded and categorised using the Theoretical Domains Framework (TDF). Prespecified criteria were used to identify key TDF domains. The second review included studies of AMS interventions. Data on effectiveness were extracted. Components of effective interventions were extracted and coded using the TDF, Behaviour Change Wheel and Behaviour Change Techniques (BCTs) taxonomy. Using prespecified matrices, we assessed the extent to which BCTs and intervention functions addressed the key TDF domains of influences on prescribing. Results: We identified 13 qualitative studies, 41 types of influences on antibiotic prescribing and 6 key TDF domains of influences: ‘beliefs about consequences’, ‘social influences’, ‘skills’, ‘environmental context and resources’, ‘intentions’ and ‘emotions’. We identified 17 research-tested AMS interventions; nine of them effective and four nationally implemented. Interventions addressed all six key TDF domains of influences. Four of these six key TDF domains were addressed by 50%–67% BCTs that were theoretically congruent with these domains, whereas TDF domain 'skills' was addressed by 24% of congruent BCTs and 'emotions' by none. Conclusions: Further improvement of antibiotic prescribing could be facilitated by: (1) national implementation of effective research-tested AMS interventions (eg, electronic decision support tools, training in interactive use of leaflets, point-of-care testing); (2) targeting important, less-addressed TDF domains (eg, 'skills', 'emotions'); (3) using relevant, under-used BCTs to target key TDF domains (eg, ‘forming/reversing habits’, ‘reducing negative emotions’, ‘social support’). These could be incorporated into existing, or developed as new, AMS interventions