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Background: Antibiotic resistance is a leading global public health concern and antibiotic use is a key driver. Effective interventions are needed to target key stakeholders, including general practitioners (GPs). In Malta, little is known about factors that influence GPs' antibiotic prescribing, making it challenging to implement targeted interventions. We therefore aimed to explore GPs' understanding of antibiotic use and resistance, and describe their perceived barriers and facilitators to prudent antibiotic prescribing for acute respiratory tract infections in Malta. Methods: Face-to-face individual semi-structured interviews were held with a quota sample of 20 GPs in 2014. Interviews were audio recorded and transcribed verbatim, and later analysed iteratively using manifest and latent content analysis. Findings were collated in a socioecological model to depict how GPs as individuals are embedded within larger social systems and contexts, and how each component within this system impacts their prescribing behaviour. Findings: We found that GPs' antibiotic prescribing decisions are complex and impacted by numerous barriers and facilitators at the individual, interpersonal, organisational, community, and public policy level. Predominant factors found to impact GPs' antibiotic prescribing included not only intrinsic GP factors such as knowledge, awareness, experience, and misconceptions, but also several external factors. At the interpersonal level, GPs' perceived patient demand and behaviour to be a persistent issue that impacts their prescribing decisions. Similarly, some GPs found pressure from drug reps to be concerning despite being considered an important source of information. Organisational and public policy-level issues such as lack of access to relevant antibiotic prescribing guidelines and current antibiotic resistance data from the community, were also considered major barriers to appropriate antibiotic prescribing. Utilisation of diagnostic testing was found to be low and GPs' perceptions on the introduction of rapid point-of-care tests to support antibiotic prescription decisions, were mixed. Conclusion: This study revealed the complexity of the antibiotic prescribing decision and the numerous barriers and facilitators that impact it, visualised through a socioecological model. Addressing GPs' antibiotic prescribing practices will require targeted and coordinated implementation activities at all levels to change behaviour and address misconceptions, whilst also improving the physical and social environment. Trial registration number: NCT03218930; https://clinicaltrials.gov/ct2/show/NCT03218930. [ABSTRACT FROM AUTHOR]

Chromatin regulation of eukaryotic genomes depends on the formation of nucleosome complexes between histone proteins and DNA. Histone variants, which are diversified by sequence or expression pattern, can profoundly alter chromatin properties. While variants in histone H2A and H3 families are well characterized, the extent of diversification of histone H2B proteins is less understood. Here, we report a systematic analysis of the histone H2B family in plants, which have undergone substantial divergence during the evolution of each major group in the plant kingdom. By characterising Arabidopsis H2Bs, we substantiate this diversification and reveal potential functional specialization that parallels the phylogenetic structure of emergent clades in eudicots. In addition, we identify a new class of highly divergent H2B variants, H2B.S, that specifically accumulate during chromatin compaction of dry seed embryos in multiple species of flowering plants. Our findings thus identify unsuspected diverse properties among histone H2B proteins in plants that has manifested into potentially novel groups of histone variants. Author summary: In addition to well-studied variants from core histones families H2A and H3, we report that land plants diversified their H2B family, leading to specialized H2B variants with specific patterns of expression, genomic distributions and properties. [ABSTRACT FROM AUTHOR]

Background: Antibiotic use is a major driver of antibiotic resistance. Although delayed antibiotic prescription is a recommended strategy to reduce antibiotic use, practices vary; it appears less commonly used in southern European countries where antibiotic consumption is highest. Despite these variations, few qualitative studies have explored general practitioners' perceptions of delayed antibiotic prescription. We therefore aimed to explore and describe the perceptions of delayed antibiotic prescription for respiratory tract infections among general practitioners in Malta. Methods: This qualitative phenomenographic study was conducted in Malta. A semi-structured interview guide was developed in English, pilot tested and revised accordingly. Interview topics included views on antibiotic resistance, antibiotic use and delayed antibiotic prescription for respiratory tract infections, and barriers and facilitators to antibiotic prescription. Individual, face-to-face interviews were held in 2014 with a quota sample of 20 general practitioners and transcribed verbatim. Data were subsequently analysed using a phenomenographic approach. Findings: General practitioners perceived delayed antibiotic prescription in five qualitatively different ways: (A) "The Service Provider"–maintaining a good general practitioner-patient relationship to retain patients and avoid doctor-shopping, (B) "The Uncertainty Avoider"–reaching a compromise and providing treatment just in case, (C) "The Comforter"–providing the patient comfort and reassurance, (D) "The Conscientious Practitioner"–empowering and educating patients, and limiting antibiotic use, and (E) "The Holder of Professional Power"–retaining general practitioner responsibility by employing a wait-and-see approach. Although general practitioners were largely positive towards delayed antibiotic prescription, not all supported the strategy; some preferred a wait-and-see approach with follow-up. Many delayed antibiotic prescription users selectively practiced delayed prescription with patients they trusted or who they believed had a certain level of knowledge and understanding. They also preferred a patient-led approach with a one to three day delay; post-dating delayed antibiotic prescriptions was uncommon. Conclusions: In this study we have shown that general practitioners hold varying perceptions about delayed antibiotic prescription and that there is variation in the way delayed antibiotic prescription is employed in Malta. Whilst delayed antibiotic prescription is utilised in Malta, not all general practitioners support the strategy, and motivations and practices differ. In high consumption settings, formal and standardised implementation of delayed antibiotic prescription could help curb antibiotic overuse. Diagnosis-specific delayed antibiotic prescription recommendations should also be incorporated into guidelines. Finally, further investigation into patients' and pharmacists' views on delayed antibiotic prescription is required. Trial registration number: NCT03218930 [ABSTRACT FROM AUTHOR]

In recent years, methicillin-resistant Staphylococcus aureus (MRSA) have become a truly global challenge. In addition to the long-known healthcare-associated clones, novel strains have also emerged outside of the hospital settings, in the community as well as in livestock. The emergence and spread of virulent clones expressing Panton-Valentine leukocidin (PVL) is an additional cause for concern. In order to provide an overview of pandemic, epidemic and sporadic strains, more than 3,000 clinical and veterinary isolates of MRSA mainly from Germany, the United Kingdom, Ireland, France, Malta, Abu Dhabi, Hong Kong, Australia, Trinidad & Tobago as well as some reference strains from the United States have been genotyped by DNA microarray analysis. This technique allowed the assignment of the MRSA isolates to 34 distinct lineages which can be clearly defined based on non-mobile genes. The results were in accordance with data from multilocus sequence typing. More than 100 different strains were distinguished based on affiliation to these lineages, SCCmec type and the presence or absence of PVL. These strains are described here mainly with regard to clinically relevant antimicrobial resistance- and virulence-associated markers, but also in relation to epidemiology and geographic distribution. The findings of the study show a high level of biodiversity among MRSA, especially among strains harbouring SCCmec IV and V elements. The data also indicate a high rate of genetic recombination in MRSA involving SCC elements, bacteriophages or other mobile genetic elements and large-scale chromosomal replacements. [ABSTRACT FROM AUTHOR]

The unique double fertilisation mechanism in flowering plants depends upon a pair of functional sperm cells. During male gametogenesis, each haploid microspore undergoes an asymmetric division to produce a large, non-germline vegetative cell and a single germ cell that divides once to produce the sperm cell pair. Despite the importance of sperm cells in plant reproduction, relatively little is known about the molecular mechanisms controlling germ cell proliferation and specification. Here, we investigate the role of the Arabidopsis male germline-specific Myb protein DUO POLLEN1, DUO1, as a positive regulator of male germline development. We show that DUO1 is required for correct male germ cell differentiation including the expression of key genes required for fertilisation. DUO1 is also necessary for male germ cell division, and we show that DUO1 is required for the germline expression of the G2/M regulator AtCycB1;1 and that AtCycB1:1 can partially rescue defective germ cell division in duo1. We further show that the male germline-restricted expression of DUO1 depends upon positive promoter elements and not upon a proposed repressor binding site. Thus, DUO1 is a key regulator in he production of functional sperm cells in flowering plants that has a novel integrative role linking gametic cell specification and cell cycle progression. [ABSTRACT FROM AUTHOR]