INTRODUCTION Colorectal cancer treatment requires a complex, multidisciplinary approach. Because of the potential variability, monitoring through clinical audits is advisable. This study assesses the effects of a quality improvement action plan in patients with locally advanced rectal cancer and treated with radiotherapy. METHODS Comparative, multicentre study in two cohorts of 120 patients each, selected randomly from patients diagnosed with rectal cancer who had initiated radiotherapy with a curative intent. Based on the results from a baseline clinical audit in 2013, a quality improvement action plan was designed and implemented; a second audit in 2017 evaluated its impact. RESULTS Standardised information was present on 77.5% of the magnetic resonance imaging (MRI) staging reports. Treatment strategies were similar in all three study centres. Of the patients whose treatment was interrupted, just 9.7% received a compensation dose. There was an increase in MRI re-staging from 32.5 to 61.5%, and a significant decrease in unreported circumferential resection margins following neoadjuvant therapy (ypCRM), from 34.5 to 5.6% (p  less then   0.001). CONCLUSIONS The comparison between two clinical audits showed improvements in neoadjuvant radiotherapy in rectal cancer patients. Some indicators reveal areas in need of additional efforts, for example to reduce the overall treatment time.One of the primary genetic risk factors for Alzheimer's disease (AD) is the presence of the Ɛ4 allele of apolipoprotein E (APOE). APOE is a polymorphic lipoprotein that is a major cholesterol carrier in the brain. It is also involved in various cellular functions such as neuronal signaling, neuroinflammation and glucose metabolism. Humans predominantly possess three different allelic variants of APOE, termed E2, E3, and E4, with the E3 allele being the most common. The presence of the E4 allele is associated with increased risk of AD whereas E2 reduces the risk. To understand the molecular mechanisms that underlie APOE-related genetic risk, considerable effort has been devoted towards developing cellular and animal models. Data from these models indicate that APOE4 exacerbates amyloid β plaque burden in a dose-dependent manner. and may also enhance tau pathogenesis in an isoform-dependent manner. Other studies have suggested APOE4 increases the risk of AD by mechanisms that are distinct from modulation of Aβ or tau pathology. Further, whether plasma APOE, by influencing systemic metabolic pathways, can also possibly alter CNS function indirectly is not complete;y understood. Collectively, the available studies suggest that APOE may impact multiple signaling pathways and thus investigators have sought therapeutics that would disrupt pathological functions of APOE while preserving or enhancing beneficial functions. This review will highlight some of the therapeutic strategies that are currently being pursued to target APOE4 towards preventing or treating AD and we will discuss additional strategies that holds promise for the future.BACKGROUND n-3 polyunsaturated fatty acids (n-3 PUFAs), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are thought to exert protective effects in cardiovascular diseases. In addition, n-3 PUFAs have demonstrated anti-cancer effects in vitro and in vivo. OBJECTIVE We investigated the anti-cancer effects and mechanism of action of EPA on PC3 prostate cancer cells in vitro. METHODS PC3 cells were treated with various concentrations of EPA, and cell survival and the abilities of migration and invasion were evaluated. The time course of the growth inhibitory effect of EPA on PC3 cells was also assessed. The mechanism underlying the anti-cancer effects of EPA was investigated by human phosphokinase and human apoptosis antibody arrays, and confirmed by western blot analysis. We also examined the contribution of reactive oxygen species (ROS) to the effects of EPA using the ROS inhibitor N-acetyl cysteine. RESULTS EPA decreased the survival of PC3 cells in a dose-dependent manner within 3 h of application, with an effective concentration of 500 μmol/L. EPA inhibited proline-rich tyrosine kinase (Pyk)2 and extracellular signal-regulated kinase 1/2 phosphorylation as determined by western blotting and the antibody arrays. The growth of PC3 cells was inhibited by EPA, which was dependent on ROS induction, while EPA inhibited Pyk2 phosphorylation independent of ROS production. CONCLUSIONS Inhibition of Pyk2 phosphorylation and ROS production contribute to the anticancer effects of EPA on PC3 cells.BACKGROUND Equitable access to services that promote health and wellbeing is an important component of social justice. A community-engaged participatory qualitative study was conducted in Flint, Michigan, USA, to understand the needs of special populations (young women, perinatal women and new mothers, older women, women with disabilities, and LGBTQIA women) and elicit their ideas about solutions. https://www.selleckchem.com/GSK-3.html METHODS In-depth interviews (n = 100) were conducted. Participants were either women living in the Flint area, human service providers in the area, or both. A team of community and academic coders analyzed the data using an a priori framework. RESULTS Participants identified needs of different groups of women and suggested ways to address them. Access to healthy food, reducing healthcare costs, and improving transportation, job opportunities and affordable quality housing were crosscutting themes across all groups of women. Mentoring support was said to protect vulnerable young women from the risk of human traffickieriences may reduce inequalities in health and wellbeing.BACKGROUND People experiencing homelessness have higher rates of problematic substance use but difficulty engaging with treatment services. There is limited evidence regarding how problematic substance use treatment should be delivered for these individuals. Previous qualitative research has explored perceptions of effective treatment by people who are homeless, but these individual studies need to be synthesised to generate further practice-relevant insights from the perspective of this group. METHODS Meta-ethnography was conducted to synthesise research reporting views on substance use treatment by people experiencing homelessness. Studies were identified through systematic searching of electronic databases (CINAHL; Criminal Justice Abstracts; Health Source; MEDLINE; PsycINFO; SocINDEX; Scopus; and Web of Science) and websites and were quality appraised. Original participant quotes and author interpretations were extracted and coded thematically. Concepts identified were compared to determine similarities and differences between studies.
INTRODUCTION Colorectal cancer treatment requires a complex, multidisciplinary approach. Because of the potential variability, monitoring through clinical audits is advisable. This study assesses the effects of a quality improvement action plan in patients with locally advanced rectal cancer and treated with radiotherapy. METHODS Comparative, multicentre study in two cohorts of 120 patients each, selected randomly from patients diagnosed with rectal cancer who had initiated radiotherapy with a curative intent. Based on the results from a baseline clinical audit in 2013, a quality improvement action plan was designed and implemented; a second audit in 2017 evaluated its impact. RESULTS Standardised information was present on 77.5% of the magnetic resonance imaging (MRI) staging reports. Treatment strategies were similar in all three study centres. Of the patients whose treatment was interrupted, just 9.7% received a compensation dose. There was an increase in MRI re-staging from 32.5 to 61.5%, and a significant decrease in unreported circumferential resection margins following neoadjuvant therapy (ypCRM), from 34.5 to 5.6% (p  less then   0.001). CONCLUSIONS The comparison between two clinical audits showed improvements in neoadjuvant radiotherapy in rectal cancer patients. Some indicators reveal areas in need of additional efforts, for example to reduce the overall treatment time.One of the primary genetic risk factors for Alzheimer's disease (AD) is the presence of the Ɛ4 allele of apolipoprotein E (APOE). APOE is a polymorphic lipoprotein that is a major cholesterol carrier in the brain. It is also involved in various cellular functions such as neuronal signaling, neuroinflammation and glucose metabolism. Humans predominantly possess three different allelic variants of APOE, termed E2, E3, and E4, with the E3 allele being the most common. The presence of the E4 allele is associated with increased risk of AD whereas E2 reduces the risk. To understand the molecular mechanisms that underlie APOE-related genetic risk, considerable effort has been devoted towards developing cellular and animal models. Data from these models indicate that APOE4 exacerbates amyloid β plaque burden in a dose-dependent manner. and may also enhance tau pathogenesis in an isoform-dependent manner. Other studies have suggested APOE4 increases the risk of AD by mechanisms that are distinct from modulation of Aβ or tau pathology. Further, whether plasma APOE, by influencing systemic metabolic pathways, can also possibly alter CNS function indirectly is not complete;y understood. Collectively, the available studies suggest that APOE may impact multiple signaling pathways and thus investigators have sought therapeutics that would disrupt pathological functions of APOE while preserving or enhancing beneficial functions. This review will highlight some of the therapeutic strategies that are currently being pursued to target APOE4 towards preventing or treating AD and we will discuss additional strategies that holds promise for the future.BACKGROUND n-3 polyunsaturated fatty acids (n-3 PUFAs), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are thought to exert protective effects in cardiovascular diseases. In addition, n-3 PUFAs have demonstrated anti-cancer effects in vitro and in vivo. OBJECTIVE We investigated the anti-cancer effects and mechanism of action of EPA on PC3 prostate cancer cells in vitro. METHODS PC3 cells were treated with various concentrations of EPA, and cell survival and the abilities of migration and invasion were evaluated. The time course of the growth inhibitory effect of EPA on PC3 cells was also assessed. The mechanism underlying the anti-cancer effects of EPA was investigated by human phosphokinase and human apoptosis antibody arrays, and confirmed by western blot analysis. We also examined the contribution of reactive oxygen species (ROS) to the effects of EPA using the ROS inhibitor N-acetyl cysteine. RESULTS EPA decreased the survival of PC3 cells in a dose-dependent manner within 3 h of application, with an effective concentration of 500 μmol/L. EPA inhibited proline-rich tyrosine kinase (Pyk)2 and extracellular signal-regulated kinase 1/2 phosphorylation as determined by western blotting and the antibody arrays. The growth of PC3 cells was inhibited by EPA, which was dependent on ROS induction, while EPA inhibited Pyk2 phosphorylation independent of ROS production. CONCLUSIONS Inhibition of Pyk2 phosphorylation and ROS production contribute to the anticancer effects of EPA on PC3 cells.BACKGROUND Equitable access to services that promote health and wellbeing is an important component of social justice. A community-engaged participatory qualitative study was conducted in Flint, Michigan, USA, to understand the needs of special populations (young women, perinatal women and new mothers, older women, women with disabilities, and LGBTQIA women) and elicit their ideas about solutions. https://www.selleckchem.com/GSK-3.html METHODS In-depth interviews (n = 100) were conducted. Participants were either women living in the Flint area, human service providers in the area, or both. A team of community and academic coders analyzed the data using an a priori framework. RESULTS Participants identified needs of different groups of women and suggested ways to address them. Access to healthy food, reducing healthcare costs, and improving transportation, job opportunities and affordable quality housing were crosscutting themes across all groups of women. Mentoring support was said to protect vulnerable young women from the risk of human traffickieriences may reduce inequalities in health and wellbeing.BACKGROUND People experiencing homelessness have higher rates of problematic substance use but difficulty engaging with treatment services. There is limited evidence regarding how problematic substance use treatment should be delivered for these individuals. Previous qualitative research has explored perceptions of effective treatment by people who are homeless, but these individual studies need to be synthesised to generate further practice-relevant insights from the perspective of this group. METHODS Meta-ethnography was conducted to synthesise research reporting views on substance use treatment by people experiencing homelessness. Studies were identified through systematic searching of electronic databases (CINAHL; Criminal Justice Abstracts; Health Source; MEDLINE; PsycINFO; SocINDEX; Scopus; and Web of Science) and websites and were quality appraised. Original participant quotes and author interpretations were extracted and coded thematically. Concepts identified were compared to determine similarities and differences between studies.
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