Macdonaldankersen0905

Owing to the rapid rise in antibiotic resistance, infectious diseases have become serious threat to public health. There is an urgent need to develop new antimicrobial agents with diverse chemical structures and novel mechanisms of action to overcome the resistance. In recent years, Quinazoline-benzimidazole hybrids have emerged as a new class of antimicrobial agents active against S. aureus and M. tuberculosis. In the current study, we designed and synthesized fifteen new Quinazoline-benzimidazole hybrids and evaluated them for their antimicrobial activity against S. aureus ATCC 29213 and M. tuberculosis H37Rv. These studies led to the identification of nine potent antibacterial agents 8a, 8b, 8c, 8d, 8f, 8g, 8h, 8i and 10c with MICs in the range of 4-64 μg/mL. Further, these selected compounds were found to possess potent antibacterial potential against a panel of drug-resistant clinical isolates which include methicillin and vancomycin-resistant S. aureus. The selected compounds were found to be less toxic to Vero cells (CC50 = 40-≥200 μg/mL) and demonstrated a favourable selectivity index. Based on the encouraging results obtained these new benzimidazol-2-yl quinazoline derivatives have emerged as promising antimicrobial agents for the treatment of MDR- S. aureus and Mycobacterial infections.Piperazine, is privileged six membered nitrogen containing heterocyclic ring also known as 1,4-Diazacyclohexane. Consequently, piperazine is a versatile medicinally important scaffold and is an essential core in numerous marketed drugs with diverse pharmacological activities. In recent years several potent molecules containing piperazine as an essential subunit of the structural frame have been reported, especially against Mycobacterium tuberculosis (MTB). read more Remarkably, a good number of these reported molecules also displayed potential activity against multidrug-resistant (MDR), and extremely drug-resistant (XDR) strains of MTB. In this review, we have made a concerted effort to retrace anti-mycobacterial compounds for the past five decades (1971-2019) specifically where piperazine has been used as a vital building block. This review will benefit medicinal chemists as it elaborates on the design, rationale and structure-activity relationship (SAR) of the reported potent piperazine based anti-TB molecules, which in turn will assist them in addressing the gaps, exploiting the reported strategies and developing safer, selective, and cost-effective anti-mycobacterial agents.The greatest challenge of 21st century biology is to fully understand mechanisms of disease to drive new approaches and medical innovation. Parallel to this is the huge biomedical endeavour of treating people through personalized medicine. Until now all CFTR modulator drugs that have entered clinical trials have been genotype-dependent. An emerging alternative is personalized/precision medicine in CF, i.e., to determine whether rare CFTR mutations respond to existing (or novel) CFTR modulator drugs by pre-assessing them directly on patient's tissues ex vivo, an approach also now termed theranostics. To administer the right drug to the right person it is essential to understand how drugs work, i.e., to know their mechanism of action (MoA), so as to predict their applicability, not just in certain mutations but also possibly in other diseases that share the same defect/defective pathway. Moreover, an understanding the MoA of a drug before it is tested in clinical trials is the logical path to drug discovery and can increase its chance for success and hence also approval. In conclusion, the most powerful approach to determine the MoA of a compound is to understand the underlying biology. Novel large datasets of intervenients in most biological processes, namely those emerging from the post-genomic era tools, are available and should be used to help in this task.Drug repurposing has increased in recent years as an attractive option for treating a number of diseases. Compared to those brought forward via traditional chemical development, drugs intended for repurposing can enter the market faster and with lower investment from pharmaceutical companies. However, a common trend is to focus on diseases that yield higher returns to the industry, such as cancer and common metabolic and inflammatory conditions, resulting in orphan illnesses and neglected tropical diseases having fewer repurposing options for affected patients. In addition, certain legal concerns, including limited patent coverage for the repurposed drugs and pharmacological challenges in performing clinical trials, reduce the likelihood of success. In this review, we discuss the most important concerns that affect the pathway of drug repurposing, with special emphasis on the economic revenues, government-industry associations, and legal considerations that together impact the pharmaceutical industry's decision-making on which compounds may be eligible for repurposing.

An ageing population and a transitioning workforce is creating demands on healthcare workforces. Clinical and procedural knowledge deficits cause anxieties in new and experienced nurses alike when integrating into new teams. Overcoming these boundaries can be achieved with Introductory programs. These develop knowledge, technical skills and non-technical skills. Investigating nurses drive to undertake such programs, and the benefits they perceive for themselves, will help to tailor future programs.

To explore post-registration nurses' motivations for undertaking an introductory program that utilised a blended learning methodology. Identifying changes in participants understanding and clinical behaviours.

An exploratory descriptive qualitative study design was used to evaluate the Introduction to Specialty Practice (ISP) program that is run by a large private healthcare provider in Melbourne, Australia. The health service includes eight campuses and four intensive care units across the group. Twelve parttheir professional identity, find their position in clinical teams, and meet the requirements of organisations.

Maintaining currency with knowledge, skills, and technological developments is crucial for nurses to consistently deliver high-level care. The demands that nurses' face within their clinical areas affects their intention to stay within the workforce and their ability to deliver care. Introductory programs that utilise blended learning strategies have a role to play in enabling nurses to create their professional identity, find their position in clinical teams, and meet the requirements of organisations.