Co-expression of CD147 (EMMPRIN), CD44v3-10, MDR1 and monocarboxylate transporters is associated with prostate cancer drug resistance and progression

Background: The aim of this study is to seek an association between markers of metastatic potential, drug resistance-related protein and monocarboxylate transporters in prostate cancer (CaP). Methods: We evaluated the expression of invasive markers (CD147, CD44v3-10), drug-resistance protein (MDR1) and monocarboxylate transporters (MCT1 and MCT4) in CaP metastatic cell lines and CaP tissue microarrays (n=140) by immunostaining. The co-expression of CD147 and CD44v3-10 with that of MDR1, MCT1 and MCT4 in CaP cell lines was evaluated using confocal microscopy. The relationship between the expression of CD147 and CD44v3-10 and the sensitivity (IC50) to docetaxel in CaP cell lines was assessed using MTT assay. The relationship between expression of CD44v3-10, MDR1 and MCT4 and various clinicopathological CaP progression parameters was examined. Results: CD147 and CD44v3-10 were co-expressed with MDR1, MCT1 and MCT4 in primary and metastatic CaP cells. Both CD147 and CD44v3-10 expression levels were inversely related to docetaxel sensitivity (IC50) in metastatic CaP cell lines. Overexpression of CD44v3-10, MDR1 and MCT4 was found in most primary CaP tissues, and was significantly associated with CaP progression. Conclusions: Our results suggest that the overexpression of CD147, CD44v3-10, MDR1 and MCT4 is associated with CaP progression. Expression of both CD147 and CD44v3-10 is correlated with drug resistance during CaP metastasis and could be a useful potential therapeutic target in advanced disease

T-cell responses to human papillomavirus type 16 among women with different grades of cervical neoplasia

Infection with high-risk genital human papillomavirus (HPV) types is a major risk factor for the development of cervical intraepithelial neoplasia (CIN) and invasive cervical carcinoma. The design of effective immunotherapies requires a greater understanding of how HPV-specific T-cell responses are involved in disease clearance and/or progression. Here, we have investigated T-cell responses to five HPV16 proteins (E6, E7, E4, L1 and L2) in women with CIN or cervical carcinoma directly ex vivo. T-cell responses were observed in the majority (78%) of samples. The frequency of CD4+ responders was far lower among those with progressive disease, indicating that the CD4+ T-cell response might be important in HPV clearance. CD8+ reactivity to E6 peptides was dominant across all disease grades, inferring that E6-specific CD8+ T cells are not vitally involved in disease clearance. T-cell responses were demonstrated in the majority (80%) of cervical cancer patients, but are obviously ineffective. Our study reveals significant differences in HPV16 immunity during progressive CIN. We conclude that the HPV-specific CD4+ T-cell response should be an important consideration in immunotherapy design, which should aim to target preinvasive disease

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Potential of epigenetic therapies in the management of solid tumors

Victor Valdespino,1 Patricia M Valdespino2 1Health Attention Department, Universidad Autónoma Metropolitana, Mexico; 2Bacterial Ecology and Epigenetics Laboratory, Universidad Nacional Autónoma de México, Mexico Abstract: Cancer is a complex disease with both genetic and epigenetic origins. The growing field of epigenetics has contributed to our understanding of oncogenesis and tumor progression, and has allowed the development of novel therapeutic drugs. First-generation epigenetic inhibitor drugs have obtained modest clinical results in two types of hematological malignancy. Second-generation epigenetic inhibitors are in development, and have intrinsically greater selectivity for their molecular targets. Solid tumors are more genetic and epigenetically complex than hematological malignancies, but the transcriptome and epigenome biomarkers have been identified for many of these malignancies. This solid tumor molecular aberration profile may be modified using specific or quasi-specific epidrugs together with conventional and innovative anticancer treatments. In this critical review, we briefly analyze the strategies to select the targeted epigenetic changes, enumerate the second-generation epigenetic inhibitors, and describe the main signs indicating the potential of epigenetic therapies in the management of solid tumors. We also highlight the work of consortia or academic organizations that support the undertaking of human epigenetic therapeutic projects as well as some examples of transcriptome/epigenome profile determination in clinical assessment of cancer patients treated with epidrugs. There is a good chance that epigenetic therapies will be able to be used in patients with solid tumors in the future. This may happen soon through collaboration of diverse scientific groups, making the selection of targeted epigenetic aberration(s) more rapid, the design and probe of drug candidates, accelerating in vitro and in vivo assays, and undertaking new cancer epigenetic-therapy clinical trails. Keywords: solid tumor, treatment, targeted therapy, epigenetic therapy&nbsp

A Pilot Study of the Effects of Mindfulness-Based Cognitive Therapy on Positive Affect and Social Anxiety Symptoms

Randomized controlled trials have demonstrated that mindfulness-based cognitive therapy (MBCT) is efficacious in reducing residual depressive symptoms and preventing future depressive episodes (Kuyken et al., 2016). One potential treatment effect of MBCT may be improvement of positive affect (PA), due to improved awareness of daily positive events (Geschwind et al., 2011). Considering social anxiety disorder (SAD) is characterized by diminished PA (Brown et al., 1998; Kashdan, 2007), we sought to determine whether MBCT would reduce social anxiety symptoms, and whether this reduction would be associated with improvement of PA deficits. Adults (N = 22) who met criteria for varied anxiety disorders participated in a small, open-label trial of an 8-week manualized MBCT intervention. Most participants presented with either a diagnosis (primary, secondary, or tertiary) of generalized anxiety disorder (GAD) (N = 15) and/or SAD (N = 14) prior to treatment, with eight individuals meeting diagnostic criteria for both GAD and SAD. We hypothesized participants would demonstrate improvements in social anxiety symptoms, which would be predicted by improvements in PA, not reductions in negative affect (NA). Results of several hierarchical linear regression analyses (completed in both full and disorder-specific samples) indicated that improvements in PA but not reductions in NA predicted social anxiety improvement. This effect was not observed for symptoms of worry, which were instead predicted by decreased NA for individuals diagnosed with GAD and both decreased NA and increased PA in the entire sample. Results suggest that MBCT may be efficacious in mitigating social anxiety symptoms, and this therapeutic effect may be linked to improvements in PA. However, further work is necessary considering the small, heterogeneous sample, uncontrolled study design, and exploratory nature of the study

Towards the construction of a carbon fluxes inventory of tropical waters: A unifying method pipeline

The relevance of inland waters in the global carbon cycle has been stressed recently, particularly because of a reassessment of their capacity for carbon exportation to the atmosphere and to the sediments. Global surveys have also highlighted the acute lack of information on tropical systems, which are exposed to crescent problems in the Global Change panorama, such as contamination and eutrophication, as well as important impacts related to water management strategies and water supply (e.g., water level fluctuations). Oxygen dynamics, a method left behind in the past, has been revised and is now being increasingly implemented to estimate primary production and ecosystemic respiration due to the urgency to understand carbon fluxes in aquatic systems. Therefore the details (advantages and disadvantages) of modern implementation of oxygen dynamics are revised and discussed here, particularly oriented to facilitate and promote their aplication in tropical aquatic systems (where it seems an adequate strategy). We suggest a unifying method pipeline in order to obtain comparable results among systems, towards the construction of a carbon flux inventory at larger (spatial and temporal) scales. This effort would contribute to understand the role and responses of tropical aquatic systems and regions (particularly as carbon sources or sinks) facing Global Change

Towards the construction of a carbon fluxes inventory of tropical waters: A unifying method pipeline

The relevance of inland waters in the global carbon cycle has been stressed recently, particularly because of a reassessment of their capacity for carbon exportation to the atmosphere and to the sediments. Global surveys have also highlighted the acute lack of information on tropical systems, which are exposed to crescent problems in the Global Change panorama, such as contamination and eutrophication, as well as important impacts related to water management strategies and water supply (e.g., water level fluctuations). Oxygen dynamics, a method left behind in the past, has been revised and is now being increasingly implemented to estimate primary production and ecosystemic respiration due to the urgency to understand carbon fluxes in aquatic systems. Therefore the details (advantages and disadvantages) of modern implementation of oxygen dynamics are revised and discussed here, particularly oriented to facilitate and promote their aplication in tropical aquatic systems (where it seems an adequate strategy). We suggest a unifying method pipeline in order to obtain comparable results among systems, towards the construction of a carbon flux inventory at larger (spatial and temporal) scales. This effort would contribute to understand the role and responses of tropical aquatic systems and regions (particularly as carbon sources or sinks) facing Global Change