In Vitro Evaluation of Vancomycin-Induced Toxicity in Human Primary Knee Chondrocytes.

Septic arthritis as a complication of orthopaedic joint surgery can have catastrophic outcomes for patients. To minimise infection risk associated with elective orthopaedics, topical vancomycin during surgery has become increasingly common. Evidence suggests that high concentrations of vancomycin, following direct application of the drug to the joint, are toxic towards various local cell types in the joint, including chondrocytes. However, the mechanism of this vancomycin tissue toxicity is yet to be determined. The aim of this study was to evaluate the toxicity of vancomycin on chondrocytes and the mechanisms of cell death involved. Human primary knee chondrocytes were exposed to vancomycin (1.25-10 mg/mL) for 24 h and their viability assessed using the resazurin reduction assay in vitro. Specific cell death mechanisms and their contributors, including reactive oxygen species (ROS) production and apoptosis, were measured. This study showed that high concentrations of vancomycin (5 and 10 mg/mL) were toxic towards human primary knee chondrocyte cells, while lower concentrations (1.25 and 2.5 mg/mL) were not. Cell death studies found that this occurred through an apoptotic pathway. This study provides additional support that vancomycin in high doses is toxic towards chondrocytes and preliminary evidence that this toxicity occurs via apoptotic cell death mechanisms.

Involvement of indoleamine 2, 3-dioxygenase (IDO) and brain-derived neurotrophic factor (BDNF) in the neuroprotective mechanisms of ferulic acid against depressive-like behaviour.

OBJECTIVE: Ferulic acid (FA) is a common food ingredient that is abundantly present in various routinely consumed food and beverages. Like many cinnamic acid derivatives, FA produces wide-ranging effects in a dose-dependent manner and various studies link FA consumption with reduced risk of depressive disorders. The aim of this study was to exploit the neuroprotective mechanisms of FA including indoleamine 2,3-dioxygenase (IDO), brain-derived neurotrophic factor (BDNF), and other pro-inflammatory cytokines by employing lipopolysaccharide (LPS)-induced depressive-like behaviour model. METHODS: C57BL/6J male mice were divided into 4 groups consisting of saline (SAL), LPS, FA and Imipramine (IMI). Animals were pretreated orally with FA (10 mg/kg) and IMI (10 mg/kg) for 21 days once daily and all groups except SAL were challenged with LPS (0.83 mg/kg) intraperitoneally on day 21. RESULTS: LPS administration produced a biphasic change in the behaviour of the animals where the animals lost a significant weight and express high immobility time at 24 h. Proinflammatory cytokines including, TNF-α, IL-6, IL-1ß, and IFN-γ were significantly increased along with increased lipid peroxidation and reduced BDNF. Furthermore, the increased kynurenine to tryptophan ratio was indicative of elevated IDO activity. CONCLUSION: The results of this study emphasise that low dose of FA is effective in attenuating depressive-like behaviour by modulating IDO, BDNF and reducing neuroinflammation.

The role of sialic acid-binding immunoglobulin-like-lectin-1 (siglec-1) in immunology and infectious disease.

Siglec-1, also known as Sialoadhesin (Sn) and CD169 is highly conserved among vertebrates and with 17 immunoglobulin-like domains is Siglec-1 the largest member of the Siglec family. Expression of Siglec-1 is found primarily on dendritic cells (DCs), macrophages and interferon induced monocyte. The structure of Siglec-1 is unique among siglecs and its function as a receptor is also different compared to other receptors in this class as it contains the most extracellular domains out of all the siglecs. However, the ability of Siglec-1 to internalize antigens and to pass them on to lymphocytes by allowing dendritic cells and macrophages to act as antigen presenting cells, is the main reason that has granted Siglec-1's key role in multiple human disease states including atherosclerosis, coronary artery disease, autoimmune diseases, cell-cell signaling, immunology, and more importantly bacterial and viral infections. Enveloped viruses for example have been shown to manipulate Siglec-1 to increase their virulence by binding to sialic acids present on the virus glycoproteins allowing them to spread or evade immune response. Siglec-1 mediates dissemination of HIV-1 in activated tissues enhancing viral spread via infection of DC/T-cell synapses. Overall, the ability of Siglec-1 to bind a variety of target cells within the immune system such as erythrocytes, B-cells, CD8+ granulocytes and NK cells, highlights that Siglec-1 is a unique player in these essential processes.

Drivers of Radioresistance in Prostate Cancer.

Prostate cancer (PCa) is the second most commonly diagnosed cancer worldwide. Radiotherapy remains one of the first-line treatments in localised disease and may be used as monotherapy or in combination with other treatments such as androgen deprivation therapy or radical prostatectomy. Despite advancements in delivery methods and techniques, radiotherapy has been unable to totally overcome radioresistance resulting in treatment failure or recurrence of previously treated PCa. Various factors have been linked to the development of tumour radioresistance including abnormal tumour vasculature, oxygen depletion, glucose and energy deprivation, changes in gene expression and proteome alterations. Understanding the biological mechanisms behind radioresistance is essential in the development of therapies that are able to produce both initial and sustained response to radiotherapy. This review will investigate the different biological mechanisms utilised by PCa tumours to drive radioresistance.

RNA-binding protein signaling in adult neurogenesis.

The process of neurogenesis in the brain, including cell proliferation, differentiation, survival, and maturation, results in the formation of new functional neurons. During embryonic development, neurogenesis is crucial to produce neurons to establish the nervous system, but the process persists in certain brain regions during adulthood. In adult neurogenesis, the production of new neurons in the hippocampus is accomplished via the division of neural stem cells. Neurogenesis is regulated by multiple factors, including gene expression at a temporal scale and post-transcriptional modifications. RNA-binding Proteins (RBPs) are known as proteins that bind to either double- or single-stranded RNA in cells and form ribonucleoprotein complexes. The involvement of RBPs in neurogenesis is crucial for modulating gene expression changes and posttranscriptional processes. Since neurogenesis affects learning and memory, RBPs are closely associated with cognitive functions and emotions. However, the pathways of each RBP in adult neurogenesis remain elusive and not clear. In this review, we specifically summarize the involvement of several RBPs in adult neurogenesis, including CPEB3, FXR2, FMRP, HuR, HuD, Lin28, Msi1, Sam68, Stau1, Smaug2, and SOX2. To understand the role of these RBPs in neurogenesis, including cell proliferation, differentiation, survival, and maturation as well as posttranscriptional gene expression, we discussed the protein family, structure, expression, functional domain, and region of action. Therefore, this narrative review aims to provide a comprehensive overview of the RBPs, their function, and their role in the process of adult neurogenesis as well as to identify possible research directions on RBPs and neurogenesis.

Putative involvement of sirtuin modulators in LPS-induced sickness behaviour in mice.

NAD+-dependent histone deacetylases (sirtuins 1-7) have been shown to be involved in various pathophysiological conditions including their involvement in cardiovascular, cancerous, neurodegenerative, immune dysregulation and inflammatory conditions. This study investigates the inflammomodulatory potential of resveratrol (RES), a sirtuin activator and sirtinol (SIR), a sirtuin inhibitor in lipopolysaccharide (LPS)-induced model of sickness behaviour in mice. Male Swiss albino mice were divided into five groups (n = 6) consisting of saline (SAL), LPS, RES, SIR, and fluoxetine (FLU) respectively, each group except LPS was prepared by intraperitoneally (i.p.) administration of SAL (10 mL/kg), RES (50 mg/kg), SIR (2 mg/kg) and FLU (10 mg/kg). Thirty minutes after the treatments, all the groups, except SAL were administered LPS (2 mg/kg, i.p.). The behavioural assays including, open field test, forced swim test, and tail suspension tests were conducted 1 h after LPS challenge. LPS administration significantly reduced the locomotor activity along with inducing a state of high immobility and that was prevented by pretreatment with RES and SIR. Further, various proinflammatory cytokines (TNF-α, IL-6, and IL-1ß), and oxidative stress markers (MDA and GSH) were found to be significantly elevated in the brain homogenates after LPS treatment. SIR pretreatment abrogated the LPS-induced neuroinflammatory and oxidative stress changes, whereas RES was only effective in reducing the oxidative stress and TNF-α levels. The results of this study speculate that the role of SIRT modulators in neuroinflammatory conditions could vary with their dose, regimen and chemical properties. Further studies with detailed molecular and pharmacokinetic profiling will be needed to explore their therapeutic potentials.

Learner attitudes towards a virtual microbiology simulation for pharmacy student education.

INTRODUCTION: Simulation for education has become popular, but much literature on this modality fails to critically examine the learner's experience, focusing instead on learning outcomes. Learner attitudes should be scrutinised and monitored to appraise a technology-enhanced learning experience as student perceived educational benefits of technology-enhanced learning is reported to be more important than the intrinsic characteristics of any particular medium or tool. This study sought to evaluate pharmacy students' attitudes toward a virtual microbiology simulation. METHODS: The virtual microbiology simulation (VUMIE) was compared with a traditional wet laboratory (lab) in a second-year integrated pharmacotherapeutics course for bachelor of pharmacy students. Data were collected using surveys deployed at baseline (pre-intervention), post-intervention (VUMIE or wet lab), and endpoint (post-interventions). Statistical and qualitative thematic analyses were performed. RESULTS: Learners found the simulation valuable, and outcomes suggest that it is possible for technology-enhanced learning activities to replace face-to-face instruction to some extent, which may be useful given the current challenges with in-person education resulting from COVID-19. More students reported a specific preference for the wet lab rather than VUMIE. CONCLUSIONS: Although technology-enhanced simulation can produce a similar learning experience to a traditional wet lab, this evidence is not sufficient to completely replace the traditional lab experience for clinical courses of study. Technology-enhanced simulation could be considered for just-in-time training before exposure to traditional lab activities, for specific skill acquisition using deliberate practice, and perhaps for standardised assessment for clinical microbiology education.

An education on pharmacologically active complementary and alternative medicine and its effects on cancer treatment: literature review.

PURPOSE: This literature review examines the provision of an education on pharmacologically active complementary and alternative medicines (CAMs), to people with cancer, their carers and oncology health professionals. METHODS: A search of the published literature between 2000 and 2020, in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, was conducted. The search retrieved 1121 studies, 1080 were excluded based on their title or abstract and 26 articles were excluded based on their text. One article was retrieved from the reference lists of the included articles and in total fifteen studies met the inclusion criteria. This review utilised Medical Education Research Quality Instrument (MERSQI) to evaluate the quality of the included studies. Four key outcomes were utilised for analysis and recommendations for future education and/or research were generated. The recommendations were graded according to the Strength of Recommendation Taxonomy (SORT). RESULTS: This review consistently found that people with cancer, their carers and oncology health professionals derived benefit from a pharmacologically active CAM education and recommends that this population receives one. Conversely, the review found many education formats utilised and no consensus on the most successful methods. CONCLUSION: Future research should examine who a CAM education should be delivered to, what type of delivery platform is most accessible and useful, and the features of the education that most increase CAM knowledge. The popularity of CAMs amongst people with cancer and the potential dangers associated with their use necessitates further research into how best to communicate CAMs to this population.

Remedial effects of caffeine against depressive-like behaviour in mice by modulation of neuroinflammation and BDNF.

Objective: Caffeine (CAF) is one of the most commonly consumed nutritional stimulant in beverages. Interestingly, CAF produces varied effects in a dose-dependent manner, and that makes it one of the most controversial nutritional ingredients. Various studies have linked CAF consumption and reduced risk of depressive disorders. The aim of this study was to investigate the effect of CAF on lipopolysaccharide (LPS)-induced neuroinflammation and depressive-like behaviour.Methods: C57BL/6J male mice were divided into four groups consisting of saline (SAL), LPS, CAF and Imipramine (IMI). Animals were pretreated orally with CAF (10 mg/kg) and IMI (10 mg/kg) for 14 days once daily and all groups except SAL were challenged with LPS (0.83 mg/kg) intraperitoneally on day 14.Results: LPS produced a biphasic behavioural response with a significantly high immobility time and weight loss after 24 h. The brain cytokines (TNF-α, IL-6, IL-1ß, and IFN-γ) levels were remarkably high, along with increased lipid peroxidation and reduced Brain Derived Neurotrophic Factor (BDNF). These biochemical and behavioural changes were significantly alleviated by CAF and IMI chronic treatment.Conclusion: The results of this study implicate that mild-moderate consumption of CAF could impart anti-inflammatory properties under neuroinflammatory conditions by modulating the cytokine and neurotrophic mechanisms.

Liraglutide modulates olfactory ensheathing cell migration with activation of ERK and alteration of the extracellular matrix.

Transplantation of olfactory ensheathing cells (OECs) is a promising approach for repairing the injured nervous system that has been extensively trialed for nervous system repair. However, the method still needs improvement and optimization. One avenue of improving outcomes is to stimulate OEC migration into the injury site. Liraglutide is a glucagon-like peptide-1 receptor agonist used for management of diabetes and obesity. It has been shown to be neuroprotective and to promote cell migration, but whether it can stimulate glial cells remains unknown. In the current study, we investigated the effects of liraglutide on OEC migration and explored the involved mechanisms. We showed that liraglutide at low concentration (100 nM) overall promoted OEC migration over time. Liraglutide modulated the migratory behavior of OECs by reducing time in arrest, and promoted random rather than straight migration. Liraglutide also induced a morphological change of primary OECs towards a bipolar shape consistent with improved migration. We found that liraglutide activated extracellular signal-regulated kinase (ERK), which has key roles in cell migration; the timing of ERK activation correlated with stimulation of migration. Furthermore, liraglutide also modulated the extracellular matrix by upregulating laminin-1 and down-regulating collagen IV. In summary, we found that liraglutide can stimulate OEC migration and re-model the extracellular matrix to better promote cell migration, and possibly also to become more conducive for axonal regeneration. Thus, liraglutide may improve OEC transplantation outcomes.

Comparison of potential pharmacokinetic drug interactions in patients with atrial fibrillation and changing from warfarin to non-vitamin K oral anticoagulant therapy.

There are now anticoagulant choices with proposed advantages of non-vitamin K oral anticoagulants (NOACs) over warfarin being less routine monitoring and less drug interactions. Interacting medication can impact the efficacy and safety of anticoagulant therapy with management remaining clinically challenging. There have been limited studies comparing the potential for pharmacokinetic (PK) drug interactions between different anticoagulants. Therefore, the aim of this study was to compare potential PK interactions in patients with atrial fibrillation (AF) changing from warfarin to NOAC therapy. A retrospective analysis was conducted of patients with AF enrolled in a dedicated warfarin program but exiting this program to commence a NOAC. Patient data was collected, and concurrent medications were utilised to identify potential PK drug interactions with both warfarin and the chosen NOAC therapy. Patients were grouped according to the number of medications with potential PK interactions and comparisons made between groups. Of the 712 eligible patients who ceased warfarin to commence a NOAC, most commenced either apixaban (45.9%) or rivaroxaban (41.9%). When comparing warfarin to NOACs, there were significant differences in the proportion of patients taking no medication with potential PK drug interactions (46.9% vs 62.8%, p < 0.0001), and taking one (35.2% vs 28.5%, p = 0.0067) and two (14.5% vs 7.3%, p < 0.0001) potentially PK interacting medications. This study found when patients with AF were switched from warfarin to a NOAC, the potential for PK drug interactions significantly reduced but remained around 40%. Identifying and managing potential PK drug interactions with NOACs remains a priority to optimise clinical benefit of these anticoagulants.

SIRT1 and SIRT2 modulators reduce LPS-induced inflammation in HAPI microglial cells and protect SH-SY5Y neuronal cells in vitro.

Neuroinflammation is associated with the development of depression. Deacetylases SIRT1 and SIRT2 are reported to exert neuroprotective effects in aging, neurogenesis, neurodegeneration and neuroinflammation. Therefore, this study aimed to investigate the effects of SIRT1 and SIRT2 modulators on LPS-induced neuroinflammation and neurodegeneration in vitro. To achieve this, HAPI rat microglial cells were pre-treated with the SIRT1 activator resveratrol (0.1-20 µM), the selective SIRT1 inhibitor EX527 (0.1; 1 µM), the dual SIRT1/SIRT2 inhibitor sirtinol (0.1-20 µM) and the SIRT2 inhibitor AGK2 (0.1; 1 µM), prior to exposure with LPS (5 ng/mL) for 20 h. The reference antidepressant drug fluoxetine and the nonsteroidal anti-inflammatory drug ibuprofen were also evaluated in the same paradigm, both at 1 µM. Resveratrol and sirtinol inhibited TNF-α production to a greater degree than either fluoxetine or ibuprofen. Resveratrol, sirtinol, EX527 and AGK2 significantly reduced PGE2 production by up to 100% in microglia. Then, the supernatant was transferred to treat SH-SY5Y cells for 24 h. In all cases, SIRT modulator pretreatment significantly protected undifferentiated SH-SY5Y human neuroblastoma cells from the insult of LPS-stimulated HAPI supernatant by up to 40%. Moreover, resveratrol and sirtinol also showed significantly better neuroprotection than fluoxetine or ibuprofen by up to 83 and 69%, respectively. In differentiated SH-SY5Y cells, only sirtinol (20, 10 µM) and AGK2 (0.1 µM) pretreatment protected the cells from LPS-stimulated HAPI supernatant. This study suggests that SIRT1 and SIRT2 modulators are effective in inhibiting LPS-stimulated production of TNF-α and PGE2 in HAPI microglial cells and protecting SH-SY5Y cells from inflammation. Thus, we provide proof of concept for further investigation of the therapeutic effect of SIRT1 and SIRT2 modulators and combination with current antidepressant medication as a treatment option.

Signalling transduction of O-GlcNAcylation and PI3K/AKT/mTOR-axis in prostate cancer.

Hexosamine biosynthetic (HBP) and PI3K/AKT/mTOR pathways are found to predominate the proliferation and survival of prostate cancer cells. Both these pathways have their own specific intermediates to propagate the secondary signals in down-stream cascades and besides having their own structured network, also have shared interconnecting branches. These interconnections are either competitive or co-operative in nature depending on the microenvironmental conditions. Specifically, in prostate cancer HBP and mTOR pathways increases the expression and protein level of androgen receptor in order to support cancer cell proliferation, advancement and metastasis. Pharmacological inhibition of a single pathway is therefore insufficient to stop disease progression as the cancer cells manage to alter the signalling channel. This is one of the primary reasons for the therapeutic failure in prostate cancer and emergence of chemoresistance. Inhibition of these multiple pathways at their common junctures might prove to be of benefit in men suffering from an advanced disease state. Hence, a thorough understanding of these cellular intersecting points and their significance with respect to signal transduction mechanisms might assist in the rational designing of combinations for effective management of prostate cancer.

SIRT1 and SIRT2 Modulators: Potential Anti-Inflammatory Treatment for Depression?

Depression is a psychiatric disorder that has a significant health burden on patients and their families. Unfortunately, the current antidepressant medications that mainly target monoamine neurotransmitters have limited efficacy. Recent evidence has indicated that neuroinflammation participates in the genesis and development of depression, and interacts with other factors involved in depression. Therefore, exploring effective anti-inflammatory medications could be beneficial for the development of new treatment options for depression. Sirtuins are a unique class of nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases, which have seven members that can affect multiple downstream targets by deacetylation activity. Among these seven members, SIRT1 and SIRT2 have been shown to participate in the pathophysiology of inflammation in numerous studies. Thus, in this short article, we review the association of SIRT1 and SIRT2 activity and depression, and evidence of the effects of SIRT1 and SIRT2 modulators on inflammation in vitro and depressive-like behaviours in vivo.

Time to Stable Therapeutic Range on Initiation of Warfarin as an Indicator of Control.

OBJECTIVES: Warfarin remains widely used with a time in therapeutic range (TiTR) above 65% recommended for best outcomes. Patients not achieving or maintaining this warfarin control may be better suited to alternate anticoagulants. Despite this, there is limited data defining a suitable trial time in patients initiating warfarin therapy, therefore the aim of this study was to determine the mean time to stable therapeutic range (TtSTR). MATERIALS AND METHODS: Retrospective data was collected for patients with atrial fibrillation enrolled in a dedicated warfarin program at a private pathology practice within 7 days of warfarin initiation. TiTR at specified timepoints was calculated and median TtSTR determined as defined by TiTR ≥ 65% over three months. Comparisons were made of populations with TtSTR above or below the median. RESULTS: The 566 patients included in the study had a mean TiTR of 64.9±16.5% at month three and median TtSTR of six months. Patients with TtSTR≤6 months achieved a mean TiTR of 68.9±12.8% at month two and maintained a TiTR over 75% from month 3 to 24. Patients with a TtSTR>6 months obtained a TiTR of 66.4±10.6% at month nine and continued to achieve lower TiTR throughout the 24 months study period. CONCLUSIONS: A majority of patients can achieve a stable TiTR above 65% within six months so review at six to nine months is likely to be a good indicator of warfarin control and to determine if patients should continue warfarin or switch to alternate anticoagulant therapy.

Liposomal doxorubicin as targeted delivery platform: Current trends in surface functionalization.

Liposomal delivery systems have significantly enhanced the efficacy and safety of chemotherapeutic agents compared to free (non-liposomal) formulations. Liposomes are vesicles made up of lipophilic bilayer and a hydrophilic core which provides perfect opportunity for their application as transport vehicle for various therapeutic and diagnostic agents. Doxorubicin is the most exploited chemotherapeutic agent for evaluation of different liposomal applications, as its physicochemical properties permit high drug entrapment and easy remote loading in pre-formulated liposomes. Pegylated liposomal doxorubicin clinically approved and, on the market, Doxil®, exemplifies the benefits offered upon the surface modification of liposome with polyethylene glycol. This unique formulation prolonged the drug residence time in the circulation and increased accumulation of doxorubicin in tumor tissue via passive targeting (enhanced permeability and retention effect). However, there is ample scope for further improvement in the efficiency of targeting tumors by coupling biological active ligands onto the liposome surface to generate intelligent drug delivery systems. Small biomolecules such as peptides, fraction of antibodies and carbohydrates have the potential to target receptors present on the surface of the malignant cells. Hence, active targeting of malignant cells using functionalised nanocarrier (liposomes encapsulated with doxorubicin) have been attempted which is reviewed in this article.

Bisubstrate Ether-Linked Uridine-Peptide Conjugates as O-GlcNAc Transferase Inhibitors.

The O-linked ß-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is a master regulator of installing O-GlcNAc onto serine or threonine residues on a multitude of target proteins. Numerous nuclear and cytosolic proteins of varying functional classes, including translational factors, transcription factors, signaling proteins, and kinases are OGT substrates. Aberrant O-GlcNAcylation of proteins is implicated in signaling in metabolic diseases such as diabetes and cancer. Selective and potent OGT inhibitors are valuable tools to study the role of OGT in modulating a wide range of effects on cellular functions. We report linear bisubstrate ether-linked uridine-peptide conjugates as OGT inhibitors with micromolar affinity. In vitro evaluation of the compounds revealed the importance of donor substrate, linker and acceptor substrate in the rational design of bisubstrate analogue inhibitors. Molecular dynamics simulations shed light on the binding of this novel class of inhibitors and rationalized the effect of amino acid truncation of acceptor peptide on OGT inhibition.

The Impact of an Evidence-Based Education on Complementary and Alternative Medicine Usage in People with Cancer: Pilot Study.

Complementary and alternative medicine (CAM) usage amongst cancer patients is high globally and in Australia. CAM use in cancer care has the ability to increase chemotherapy toxicity or cause sub-therapy due to altered metabolism as well as increase a patient's bleeding risk. Furthering these risks, people with cancer are largely obtaining their CAM use information from non-evidence-based sources. This study aimed to determine whether the implementation of a CAM education influenced decision-making with regard to CAM usage amongst cancer patients. Twenty people with cancer were recruited for participation in this study. The aims of this study were achieved by surveying patients via questionnaire, both prior to and following receiving an evidence-based CAM education, in either or both written or audiovisual format. This exploratory study found, consistent with the literature, that the majority of participants were obtaining their CAM use information from non-evidenced-based sources. Additionally, it found that the participants wanted more CAM use information and that they demonstrated some altered decision-making after receiving evidenced-based information. On the post-educational questionnaire, the number of participants that stated that they would use CAMs decreased by almost 14%, and some participants made CAM use decisions in accordance with the information provided in the resources. Furthermore, a small increase in CAM knowledge was demonstrated, and it was reported that the resource had prompted them to look further into CAM information. Lastly, the participants in this study found the resource to be mostly useful and helpful and preferred the animated video to the written information.

Quinazoline alpha-adrenoreceptor blockers as an adjunct cancer treatment: From bench to bedside.

Drug repurposing has been increasingly used by both researchers and clinicians to identify new cancer treatments. The alpha-1 adrenoreceptor blockers are a class of drugs that have been used for many years in the treatment of hypertension and benign prostatic hyperplasia. Some of the drugs in this class, notably the quinazoline derivatives, have been found to display cytotoxic properties, identifying them as potential options in the treatment of cancer. This review will examine the currently available evidence that investigates the cytotoxic and anti-cancer properties of these agents, the mechanisms behind these properties and how the alpha-1 blockers fit within current cancer therapies. It aims to answer the question of whether these agents can go from the laboratory bench top into cancer clinics.

Barriers and Strategies for Improving Medication Adherence Among People Living With COPD: A Systematic Review.

BACKGROUND: While medication is an integral component of the effective management of COPD, contemporary studies report that more than half of all people who are prescribed medication for the management of their COPD do not adhere to therapy. Enhancing medication adherence and improving health outcomes for those living with COPD are among the key challenges for the global health community. This systematic review aims to identify the rate of nonadherence among people who are prescribed controller medication for the management of their COPD, and identifies the barriers and facilitators that influence their medication use behavior. METHODS: A systematic search of medical databases (ie, MEDLINE, CINHAL, and EMBASE) was conducted using key words to identify literature in the English language, published between January 2003 and December 2019. Included studies were assessed for quality using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist. RESULTS: A total of 1,474 studies were identified from the initial database search, of which 38 met the inclusion criteria. Of these 38 studies, 37 reported on rates of nonadherence (ranging from 22% to 93%), 30 reported on barriers to adherence, 24 reported on enablers to adherence, and 16 reported on both. The majority (33) of the studies were conducted in high-income nations. The quality of articles ranged from 47% to 90%. Medication-taking behavior was reported to be influenced by several factors such as subjects' beliefs about medication, their experiences of and satisfaction with medication effectiveness, their concerns regarding medication side effects, their personal circumstances, habits and health status, and their relationships with health care providers. CONCLUSIONS: Adherence to COPD medication was generally low, with the majority of studies identifying the presence of depression and subjects' concern about the harmful effects of the medicine as barriers to adherence. Variability exists on the reported rates of nonadherence, possibly due to different measures utilized to assess adherence. Future research in low-income nations is needed.