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Implementing antimicrobial stewardship (AMS) programs is central to optimise antimicrobial use in primary care. This study aims to assess general practitioners' (GPs') awareness of AMS, uptake of AMS strategies, attitudes towards GP-pharmacist collaboration in AMS and future AMS improvement strategies. A paper-based survey of nationally representative GPs across Australia was conducted in 2019. Tofacitinib chemical structure Of 386 respondent GPs, 68.9% were familiar with AMS. Respondents most frequently used the Therapeutic Guidelines (TG) (83.2%, 321/385) and delayed antimicrobial prescribing (72.2%, 278/385) strategies, whereas few utilised point-of-care tests (18.4%, 71/382), patient information leaflets (20.2%, 78/384), peer prescribing reports (15.5%, 60/384) and audit and feedback (9.8%, 38/384). GPs were receptive to pharmacists' recommendations on the choice (50.5%, 192/381) and dose (63%, 241/382) of antimicrobials, and more than 60% (235/381) supported a policy fostering increased GP-pharmacist collaboration. Most GPs agreed to have AMS training (72%, 278/386), integration of electronic TG (eTG) with prescribing software (88.3%, 341/386) and policies limiting the prescribing of selected antimicrobials (74.4%, 287/386) in the future. Conclusively, GPs are aware of the importance of judicious antimicrobial prescribing but inadequately uptake evidence-based AMS strategies. The majority of GPs support GP-pharmacist collaborative AMS approaches to optimise antimicrobial use. Developing a feasible GP-pharmacist collaborative AMS implementation model and facilitating stewardship resources and training could foster AMS activities in primary care.Multiple sclerosis (MS) is an autoimmune and demyelinating disease of the central nervous system. Although the etiology of MS is still unknown, both genetic and environmental factors contribute to the pathogenesis of the disease. Acetylcholine participates in the modulation of central and peripheral inflammation. The cells of the immune system, as well as microglia, astrocytes and oligodendrocytes express cholinergic markers and receptors of muscarinic and nicotinic type. The role played by acetylcholine in MS has been recently investigated. In the present review, we summarize the evidence indicating the cholinergic dysfunction in serum and cerebrospinal fluid of relapsing-remitting (RR)-MS patients and in the brains of the MS animal model experimental autoimmune encephalomyelitis (EAE). The correlation between the increased activity of the cholinergic hydrolyzing enzymes acetylcholinesterase and butyrylcholinesterase, the reduced levels of acetylcholine and the increase of pro-inflammatory cytokines production were recently described in immune cells of MS patients. Moreover, the genetic polymorphisms for both hydrolyzing enzymes and the possible correlation with the altered levels of their enzymatic activity have been also reported. Finally, the changes in cholinergic markers expression in the central nervous system of EAE mice in peak and chronic phases suggest the involvement of the acetylcholine also in neuro-inflammatory processes.Oral health is considered an important factor of general health and it contributes to the quality of life. Despite the raising awareness of preventive measures, the prevalence of oral health conditions continues to increase. In this context, a growing interest in investigating natural resources like Vitis vinifera (V. vinifera) phenolic compounds (PhCs) as oral health promoters has emerged. This paper aims to review the evidence about the bioactivities of V. vinifera by-products in oral health. Up to date, a high number of studies have thoroughly reported the antimicrobial and antiplaque activity of V. vinifera extracts against S. mutans or in multi-species biofilms. Moreover, the bioactive compounds from V. vinifera by-products have been shown to modulate the periodontal inflammatory response and the underlying oxidative stress imbalance induced by the pathogenic bacteria. Considering these beneficial effects, the utility of V. vinifera by-products in the maintaining of oral health and the necessary steps towards the development of oral care products were emphasized. In conclusion, the high potential of V. vinifera by-products could be valorized in the development of oral hygiene products with multi-target actions in the prevention and progression of several oral conditions.Drought stress is a major environmental stress, which adversely affects the biological and molecular processes of plants, thereby impairing their growth and development. In the present study, we found that the expression level of OsTBP2.2 which encodes for a nucleus-localized protein member belonging to transcription factor IID (TFIID) family, was significantly induced by polyethylene glycol (PEG) treatment. Therefore, knockdown mutants of OsTBP2.2 gene were generated to investigate the role of OsTBP2.2 in rice response to drought stress. Under the condition of drought stress, the photosynthetic rate, transpiration rate, water use efficiency, and stomatal conductance were significantly reduced in ostbp2.2 lines compared with wild type, Dongjin (WT-DJ). Furthermore, the RNA-seq results showed that several main pathways involved in "MAPK (mitogen-activated protein kinase) signaling pathway", "phenylpropanoid biosynthesis", "defense response" and "ADP (adenosine diphosphate) binding" were altered significantly in ostbp2.2. We also found that OsPIP2;6, OsPAO and OsRCCR1 genes were down-regulated in ostbp2.2 compared with WT-DJ, which may be one of the reasons that inhibit photosynthesis. Our findings suggest that OsTBP2.2 may play a key role in rice growth and the regulation of photosynthesis under drought stress and it may possess high potential usefulness in molecular breeding of drought-tolerant rice.Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive solid malignancies due to the rapid rate of metastasis and high resistance to currently applied cancer therapies. The complex mechanism underlying the development and progression of PDAC includes interactions between genomic, epigenomic, and signaling pathway alterations. In this review, we summarize the current research findings on the deregulation of epigenetic mechanisms in PDAC and the influence of the epigenome on the dynamics of the gene expression changes underlying epithelial-mesenchymal transition (EMT), which is responsible for the invasive phenotype of cancer cells and, therefore, their metastatic potential. More importantly, we provide an overview of the studies that uncover potentially actionable pathways. These studies provide a scientific basis to test epigenetic drug efficacy in synergy with other anticancer therapies in future clinical trials, in order to reverse acquired therapy resistance. Thus, epigenomics has the potential to generate relevant new knowledge of both a biological and clinical impact.

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