Penehyclidine for Prevention of Postoperative Nausea and Vomiting in Patients Undergoing Gynecological Laparoscopic Surgery Under Combined Intravenous and Inhalation Anesthesia: A Randomized, Double-Blind, Placebo-Controlled Trial.

Purpose: We designed this study to investigate the effect of intravenous use of penehyclidine on postoperative nausea and vomiting (PONV) after gynecological laparoscopic surgery. Patients and Methods: Ninety-two Women Patients (Aged ≥ 18) Scheduled for Elective Gynecologic Laparoscopy Were Enrolled in the Current Study. Patients Were Equally Randomized Assigned Into Penehyclidine group (PHC group: received a bolus of penehyclidine 10 µg/kg during the induction of anesthesia, then followed by a continuous infusion of 10 µg/kg penehyclidine at a fixed rate of 2.0 mL/h in postoperative intravenous analgesia pump over 48h, 0.5 mg upper limit respectively) or Control group (received 0.9% saline in replace of penehyclidine at the same time points). The primary outcome measure was the incidence of postoperative nausea and vomiting in the postanesthesia care unit and ward area. Quality of Recovery-15 (QoR-15) scores and general comfort questionnaire (GCQ) scores were assessed on postoperative day (POD) 1, 2. Results: Patients between two groups had comparable baseline characteristics. Compared with the Control group, the incidence and severity of PONV, postoperative nausea (PON), and postoperative vomiting (POV) were significantly lower in the PHC group at 2h (PONV: P = 0.002, P = 0.004, respectively; PON: P = 0.018, P = 0.038, respectively; POV: P = 0.011, P = 0.072, respectively), 24h (PONV: P = 0.003, P = 0.001, respectively; PON: P = 0.010, P = 0.032, respectively; POV: P = 0.006, P = 0.044, respectively), and 48h (PONV: P = 0.003, P = 0.002, respectively; PON: P = 0.007, P = 0.019, respectively; POV: P = 0.002, P = 0.013, respectively) after surgery. The QoR-15 and GCQ scores of the PHC group were significantly higher than those of the Control group at POD 1, 2 (P < 0.001; P < 0.001, respectively). Conclusion: Our findings suggest that perioperative intravenous application of penehyclidine can effectively prevent postoperative nausea and vomiting in gynecological laparoscopic surgery patients and improve postoperative recovery.

Harnessing PD-1 cell membrane-coated paclitaxel dimer nanoparticles for potentiated chemoimmunotherapy.

Chemoimmunotherapy has emerged as a promising strategy for improving the efficacy of cancer treatment. Herein, we present PD-1 receptor-presenting membrane-coated paclitaxel dimers nanoparticles (PD-1@PTX2 NPs) for enhanced treatment efficacy. PD-1 cell membrane-cloaked PTX dimer exhibited effective cellular uptake and increased cytotoxicity against cancer cells. PD-1@PTX2 NPs could selectively bind with PD-L1 ligands expressed on breast cancer cells. Our nanoparticles exhibit a remarkable tumor growth inhibition rate of 71.3% in mice bearing 4T1 xenografts and significantly prolong survival in mouse models of breast cancer. Additionally, our nanoparticles promoted a significant 3.2-fold increase in CD8+ T cell infiltration and 73.7% regulatory T cell (Treg) depletion within tumors, boosting a robust antitumor immune response. These findings underscore the potential of utilizing immune checkpoint receptor-presented PTX nanoparticles to enhance the efficacy of chemoimmunotherapy, providing an alternative approach for improving cancer treatment.

Interactome between ASFV and host immune pathway proteins.

IMPORTANCE: African swine fever (ASF), caused by African swine fever virus (ASFV), has become a major crisis for the pork industry in recent years. The mechanism for ASFV pathology and the clinical symptoms difference of ASF between domestic pigs and reservoir hosts remain to be elucidated. We deciphered the comprehensive protein-protein interaction (PPI) network between ASFV and host immune pathways. The intensive PPI network contained both ASFV-host immune pathway PPI and ASFV-ASFV PPI information, providing a comprehensive ASFV-host interaction landscape. Furthermore, the ASFV-host PPI difference between domestic pigs and warthogs was explored, which will be instructive for exploring essential candidates involved in ASFV pathology. Moreover, we screened the inhibitory effect of ASFV proteins in the PPI with cGAS-STING pathway on IFN-I and NF-κB, further providing possible functions of ASFV-host PPI network in innate immune regulation.

[Preparation and Tumor Targeting Analysis of Cell Membrane Nanovesicles Derived from Breast Cancer Cells].

Objective: To prepare cell membrane nanovesicles (NVs) derived from breast cancer cells, to explore their basic characteristics, tumor cell endocytosis, and in vivo distribution in a tumor-bearing mouse model, and to investigate their tumor targeting properties. Methods: 4T1 breast cancer cells were cultured in vitro. The cell membrane of 4T1 cells was isolated through ultracentrifugation and NVs were formulated with a liposome extruder. The size distribution of NVs was determined by way of dynamic light scattering, and the morphology properties of the NVs were examined with transmission electron microscope. The stability of NVs was analyzed by measuring the diameter changes of NVs submerged in phosphate-buffered saline (PBS). The biocompatibility of NVs was investigated by measuring the viability of dendritic cells treated with NVs at different concentrations (5, 10, 20, 50, and 100 mg·L -1) by CCK-8 assay. Fluorescence microscopy was used to analyze the cellular uptake of NVs by breast cancer cells. A mice model of breast cancer model was established with mice bearing subcutaneous xenograft of 4T1 cells. The mice were treated with Cy5.5-labeled NVs injected via the tail vein and the in vivo distribution of NVs was analyzed with an imaging system for small live animals. Results: The results showed that NVs derived from 4T1 breast cancer cells were successfully prepared. The NVs had a mean diameter of 123.2 nm and exhibited a hollow spherical structure under transmission electron microscope. No obvious change in the size of the NVs was observed after 7 days of incubation in PBS solution. CCK-8 assay results showed that the viability of dendritic cells treated with NVs at different concentrations was always higher than 90%. Fluorescence microscopic imaging showed that NVs could be efficiently internalized into breast cancer cells. in vivo biodistribution analysis revealed that breast cancer cell-derived NVs showed higher distribution in tumor tissue than the NVs prepared with normal cells did. Conclusion: We successfully prepared cell membrane NVs derived from 4T1 breast cancer cells. These NVs had efficient cellular uptake by breast cancer cells and sound tumor targeting properties.

Structure-dependent mechanical properties of self-folded two-dimensional nanomaterials.

The design of self-folded two-dimensional nanomaterials (SF-2DNMs) has been proposed to greatly enhance the ductility of two-dimensional material assemblies. However, the dependences of the mechanical properties of SF-2DNMs on the folded geometries have not been fully clarified. In this paper, we develop a theoretical model to describe the mechanical properties of SF-2DNMs based on the shear-lag analysis. With this model, the load transfer behaviors in SF-2DNMs are demonstrated. The Young's modulus and tensile strength of SF-2DNMs are found to increase and then converge with the fold length, which agree well with the results of molecular dynamics simulations. Moreover, the phase diagrams of failure modes are obtained for SF-2DNMs and their stacked assemblies, providing design criteria for the geometries of SF-2DNMs. The structure-property relationship revealed in our study will provide useful guidelines for the structure design and property optimization of SF-2DNMs.

2D-Topology-Seeded Graphitization for Highly Thermally Conductive Carbon Fibers.

Highly thermally conductive carbon fibers (CFs) have become an important material to meet the increasing demand for efficient heat dissipation. To date, high thermal conductivity has been only achieved in specific pitch-based CFs with high crystallinity. However, obtaining high graphitic crystallinity and high thermal conductivity beyond pitch-CFs remains a grand challenge. Here, a 2D-topology-seeded graphitization method is presented to mediate the topological incompatibility in graphitization by seeding 2D graphene oxide (GO) sheets into the polyacrylonitrile (PAN) precursor. Strong mechanical strength and high thermal conductivity up to 850 W m- 1 K-1 are simultaneously realized, which are one order of magnitude higher in conductivity than commercial PAN-based CFs. The self-oxidation and seeded graphitization effect generate large crystallite size and high orientation to far exceed those of conventional CFs. Topologically seeded graphitization, verified in experiments and simulations, allows conversion of the non-graphitizable into graphitizable materials by incorporating 2D seeds. This method extends the preparation of highly thermally conductive CFs, which has great potential for lightweight thermal-management materials.

The preclinical inhibitor GS441524 in combination with GC376 efficaciously inhibited the proliferation of SARS-CoV-2 in the mouse respiratory tract.

The unprecedented coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a serious threat to global public health. Development of effective therapies against SARS-CoV-2 is urgently needed. Here, we evaluated the antiviral activity of a remdesivir parent nucleotide analog, GS441524, which targets the coronavirus RNA-dependent RNA polymerase enzyme, and a feline coronavirus prodrug, GC376, which targets its main protease, using a mouse-adapted SARS-CoV-2 infected mouse model. Our results showed that GS441524 effectively blocked the proliferation of SARS-CoV-2 in the mouse upper and lower respiratory tracts via combined intranasal (i.n.) and intramuscular (i.m.) treatment. However, the ability of high-dose GC376 (i.m. or i.n. and i.m.) was weaker than GS441524. Notably, low-dose combined application of GS441524 with GC376 could effectively protect mice against SARS-CoV-2 infection via i.n. or i.n. and i.m. treatment. Moreover, we found that the pharmacokinetic properties of GS441524 is better than GC376, and combined application of GC376 and GS441524 had a synergistic effect. Our findings support the further evaluation of the combined application of GC376 and GS441524 in future clinical studies.

Sufentanil Protects the Liver from Ischemia/Reperfusion-Induced Inflammation and Apoptosis by Inhibiting ATF4-Induced TP53BP2 Expression.

Liver ischemia-reperfusion (I/R) injury is a pathological process that often occurs during liver and trauma surgery. This study aimed to investigate the protective effect and potential mechanisms of sufentanil on hepatic I/R injury. I/R rat model and hypoxic/reoxygenation (H/R)-induced buffalo rat liver (BRL)-3A cell model were established. Following pretreatment with sufentanil, the enzymatic activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in rat serum and the changes of hepatic histopathology were evaluated to track the extent of liver injury. The levels of inflammatory factors were determined with ELISA kits and RT-qPCR. The infiltration of macrophages was assessed after detecting monocyte chemoattractant protein 1 (MCP-1) and F4/80 expression. Additionally, apoptosis was measured by means of TUNEL staining, and gene expression related to apoptosis was examined using RT-qPCR and western blotting. Then, TP53BP2 was overexpressed in BRL-3A cells exposed to H/R condition to evaluate whether sufentanil defended the liver against injury by regulating TP53BP2 expression. Moreover, the potential binding site of ATF4 on the TP53BP2 promoter was analyzed using JASPAR databases and verified by chromosomal immunoprecipitation (ChIP) assay. Furthermore, TP53BP2 expression and endoplasmic reticulum stress (ERS)-related protein levels were determined after ATF4 was overexpressed in sufentanil-treated BRL-3A cells. Results revealed that sufentanil significantly improved hepatic I/R injury, decreased the levels of inflammatory factors, and alleviated hepatocyte apoptosis. Notably, upregulated TP53BP2 expression was observed in hepatic tissues, and TP53BP2 overexpression markedly reversed the protective effects of sufentanil on the inflammation and apoptosis in H/R-stimulated BRL-3A cells. Additionally, ATF4 was confirmed to combine with the TP53BP2 promoter. ATF4 upregulation attenuated the inhibitory effects of sufentanil on the expression of TP53BP2 and ERS-associated proteins. These findings demonstrated that sufentanil protects the liver from inflammation and apoptosis injury induced by I/R by inhibiting ATF4 expression and further suppressing TP53BP2 expression, suggesting a promising therapeutic candidate for the treatment of liver I/R injury.

The structural basis of African swine fever virus core shell protein p15 binding to DNA.

African swine fever (ASF) is an acute, hemorrhagic, and highly contagious disease caused by African swine fever virus (ASFV). The mortality rate of acute infection up to 100% have posed an unprecedented challenge of the swine industry. Currently no commercial antiviral drug is available for the control and treatment of ASFV. The structural resolution of ASFV virions reveals the details of ASFV morphogenesis, providing a new perspective for the research and promotion of the development of ASFV vaccines. Although the architecture of ASFV have been solved via cryo-EM, the structural details of four of the five viral layers remain unclear (except the outer capsid). In this study, we resolved the crystal structure of the ASFV core shell protein p15. The secondary structural elements of a protomer include four α-helix structures and six antiparallel ß-strands. Further analysis revealed that ASFV p15 forms disulfide-linked trimers between the Cys9 from one protomer and Cys30 from other protomer. Additionally, the nucleic acid-binding property was characterized by electrophoretic mobility shift assay. Two critical amino acid Lys10 and Lys39 have been identified which is essential to the nucleic acid-binding affinity of ASFV p15. Together, these findings may provide new insight into antiviral drug development.

Insight into vaccine development for Alpha-coronaviruses based on structural and immunological analyses of spike proteins.

Coronaviruses that infect humans belong to the Alpha-coronavirus (including HCoV-229E) and Beta-coronavirus (including SARS-CoV and SARS-CoV-2) genera. In particular, SARS-CoV-2 is currently a major threat to public health worldwide. The spike (S) homotrimers bind to their receptors via the receptor-binding domain (RBD), which is a major target to block viral entry. In this study, we selected Alpha-coronavirus (HCoV-229E) and Beta-coronavirus (SARS-CoV and SARS-CoV-2) as models. Their RBDs exist two different conformational states (lying or standing) in the prefusion S-trimer structure. Then, the differences in the immune responses to RBDs from these coronaviruses were analyzed structurally and immunologically. Our results showed that more RBD-specific antibodies (antibody titers: 1.28×105; 2.75×105) were induced by the S-trimer with the RBD in the "standing" state (SARS-CoV and SARS-CoV-2) than the S-trimer with the RBD in the "lying" state (HCoV-229E, antibody titers: <500), and more S-trimer-specific antibodies were induced by the RBD in the SARS-CoV and SARS-CoV-2 (antibody titers: 6.72×105; 5×105) than HCoV-229E (antibody titers:1.125×103). Besides, we found that the ability of the HCoV-229E RBD to induce neutralizing antibodies was lower than S-trimer, and the intact and stable S1 subunit was essential for producing efficient neutralizing antibodies against HCoV-229E. Importantly, our results reveal different vaccine strategies for coronaviruses, and S-trimer is better than RBD as a target for vaccine development in Alpha-coronavirus Our findings will provide important implications for future development of coronavirus vaccines.Importance Outbreak of coronaviruses, especially SARS-CoV-2, poses a serious threat to global public health. Development of vaccines to prevent the coronaviruses that can infect humans has always been a top priority. Coronavirus spike (S) protein is considered as a major target for vaccine development. Currently, structural studies have shown that Alpha-coronavirus (HCoV-229E) and Beta-coronavirus (SARS-CoV and SARS-CoV-2) RBDs are in "lying" and "standing" states in the prefusion S-trimer structure. Here, we evaluated the ability of S-trimer and RBD to induce neutralizing antibodies among these coronaviruses. Our results showed that the S-trimer and RBD are both candidates for subunit vaccines in Beta-coronavirus (SARS-CoV and SARS-CoV-2) with a RBD "standing" state. However, for Alpha-coronavirus (HCoV-229E) with a RBD "lying" state, the S-trimer may be more suitable for subunit vaccines than the RBD. Our results will provide novel ideas for the development of vaccines targeting S protein in the future.

Unveiling the mechanism of structure-dependent thermal transport behavior in self-folded graphene film: a multiscale study.

Understanding the relationship between the microstructures and overall properties is one of the basic concerns for material design and applications. As a ubiquitous structural configuration in nature, the folded morphology is also widely observed in graphene-based nanomaterials, namely grafold. Recently, a self-folded graphene film (SF-GF) material has been successfully fabricated by the assembly of grafolds and exhibits promising applications in thermal management. However, the dependence of thermal properties of SF-GF on the structural features of grafold has remained unclear. We here develop a theoretical model to describe the thermal transport behavior in SF-GF. Our model demonstrates the relationship between the fold length of grafolds and thermal properties of SF-GF. It serves as an efficient and portable tool to predict the temperature profile and thermal conductivity of SF-GF with good validations by large-scale molecular dynamics simulations. Using this model, we further study the evolution of thermal conductivity of SF-GF with the unfolding deformation during the stretch. Moreover, the effect of geometrical irregularity of grafolds is uncovered. The model developed in this work not only provides practical guidelines for the manipulation and design of thermal properties of SF-GF, but also benefits the understanding of thermal transport behaviors in other two-dimensional nanomaterials with folded structures.

Japanese encephalitis virus induces apoptosis by inhibiting Foxo signaling pathway.

Japanese encephalitis virus (JEV) infection induces brain tissue disease characterized by neuron death. however, little is known about the underlying mechanism. Using RNA sequencing, we profiled global mRNA expression changes in response to in vitro and in vivo JEV infection. Integration analysis of in vitro and in vivo mRNA transcriptome revealed that JEV infection regulated apoptosis-related Foxo signaling pathway. Foxo expression was reduced by JEV infection in vitro and in vivo. Knockdown of Foxo promoted apoptosis, while its overexpression reduced apoptosis in JEV-infected Neuro-2a cells. JEV infection in Neuro-2a cells decreased the expression of Foxo downstream genes including pro-apoptotic protein Bim, anti-apoptotic protein Bcl-6 and p21. Overexpression of anti-apoptotic proteins Bcl-6 and p21 repressed JEV-induced apoptosis. These findings suggest that Foxo primarily exerts an anti-apoptotic function via Bcl-6 and p21 in JEV-infected Neuro-2a cells. A STAT3 binding site was identified in the promoter region of Foxo by TFBIND software and confirmed by ChIP and reporter assays. JEV infection reduced STAT3 expression as well as its binding at the Foxo promoter compared to mock infection in Neuro-2a cells. Moreover, STAT3 knockdown reduced Foxo promoter activity and Foxo expression. Therefore, JEV reduced Foxo expression, at least in part, by downregulating STAT3. Taken together, we found that JEV induced cell apoptosis by inhibiting STAT3-Foxo-Bcl-6/p21 pathway, which provides a novel insight into JEV-caused encephalitis.

Hepatitis C virus and its protein NS4B activate the cancer-related STAT3 pathway via the endoplasmic reticulum overload response.

Oxidative stress induces the activation of signal transducer and activator of transcription 3 (STAT3), which plays an important role in hepatocellular carcinoma (HCC). We have previously reported that hepatitis C virus (HCV) and its protein NS4B induce the production of reactive oxygen species (ROS) via the endoplasmic reticulum overload response (EOR) in human hepatocytes. Here, we found that NS4B and HCV induce STAT3 activation and stimulate the expression of cancer-related STAT3 target genes, including VEGF, c-myc, MMP-9 and Mcl-1, by EOR in human hepatocytes. Moreover, the cancer-related STAT3 pathway activated by NS4B and HCV via EOR were found to promote human hepatocyte viability. Taken together, these findings revealed that HCV NS4B might contribute to HCC by activating the EOR-mediated cancer-related STAT3 pathway, and this could provide novel insights into HCV-induced HCC.

Japanese encephalitis virus induces apoptosis by the IRE1/JNK pathway of ER stress response in BHK-21 cells.

The role of endoplasmic reticulum (ER) stress in Japanese encephalitis is largely unknown. In this study, we found that Japanese encephalitis virus (JEV) strain SA14-14-2 regulates the expression of glucose-regulated protein 78 (GRP78), transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP), and splicing of X-box-binding protein 1 (XBP1) mRNA in BHK-21 cells. SA14-14-2-induced cytopathic effect and decrease in viability were also observed. Moreover, the inositol-requiring enzyme 1 (IRE1) inhibitor 3,5-dibromosalicylaldehyde and JNK inhibitor SP600125 increased cell viability and reduced cell apoptosis but did not alter virus replication in SA14-14-2-infected BHK-21 cells. These results, for the first time, demonstrate that JEV induces apoptosis by the IRE1/JNK pathway of ER stress response.

STAT3 cooperates with Twist to mediate epithelial-mesenchymal transition in human hepatocellular carcinoma cells.

Epithelial-to-mesenchymal transition (EMT) is critical for the invasion and metastasis of hepatocellular carcinoma (HCC). However, to date, the association of signal transducer and activator of transcription 3 (STAT3) with EMT, and its mediated tumor invasion and metastasis in HCC, remain elusive. We investigated the relationship between STAT3 activation and EMT, and the underlying mechanisms involved in HCC progression. By stable transfection, we successfully overexpressed STAT3 in low metastatic SMMC7721 cells and silenced STAT3 expression in high metastatic MHCC97H cells. The EMT-associated molecular HCC cell changes were analyzed by real-time PCR, western blotting and immunocytochemical methods. The EMT-mediated HCC cell invasion and migration were evaluated by a Transwell cell invasion and cell migration assay, respectively. The interaction between STAT3 and Twist (a key EMT inducer) was evaluated by dual-luciferase reporter assay. In the present study, we found that STAT3 overexpression significantly reduced E-cadherin and ß-cadherin, and it enhanced N-cadherin and vimentin expression in the SMMC7721 cells. STAT3 knockdown significantly increased E-cadherin and ß-cadherin, and it decreased N-cadherin and vimentin expression in the MHCC97H cells. Meanwhile, a dual-luciferase reporter assay revealed that STAT3 may bind the Twist promoter, mediate its transcriptional activity, and then promote the EMT process in HCC cells. STAT3 activation-mediated EMT also evidently enhanced HCC cell invasion and migration. In summary, the present study demonstrated for the first time that STAT3 may cooperate with Twist to mediate EMT and induce HCC invasion and metastasis. Activated STAT3, Twist, and EMT markers may serve as potential molecular targets in the prevention and/or treatment of HCC invasion and metastasis.

Anatomical right hemicolectomy: a novel surgical method and its clinical application.

BACKGROUND/AIMS: Presently, the notion of traditional right hemicolectomy has not met the rapidly developed requirements for precise gastrointestinal surgical procedures. In this study, we introduced a novel surgical method, namely "anatomical right hemicolectomy," and evaluated the safety and short-term effects of this method for the treatment of right hemicolon carcinoma. METHODOLOGY: The clinical data of 10 cases with progressive right hemicolon carcinoma underwent anatomical right hemicolectomy from January 2013 to February 2014 were collected and analyzed retrospectively. RESULTS: All the operations were successfully completed. The number of cleared lymph nodes was 18.0±6.7, the mean operative time was 162.7±25.3 mins, the mean blood loss was 95.2±32.5 ml, time to first flatus was 4.2±1.9 days, and the mean size of tumor was 4.96±3.2 cm. In these 10 patients, there was no case of respiratory infections, intestinal obstruction, anastomotic bleeding, anastomotic stricture, anastomotic leakage and other complications. All patients recovered, and subsequently discharged. CONCLUSIONS: In summary, anatomical right hemicolectomy was a safe and feasible method for the treatment of progressive right hemicolon carcinoma; it was worth popularizing widely.

STAT3 activation mediates epithelial-to-mesenchymal transition in human hepatocellular carcinoma cells.

BACKGROUND/AIMS: Epithelial-to-mesenchymal transition (EMT) is critical for the development of the invasion and metastasis in human cancers. Recently, signal transducer and activator of transcription 3 (STAT3) activation has been linked to EMT program in breast cancer. However, the actual association of STAT3 activation with EMT, and its mediated tumor invasion and metastasis remains elusive in hepatocellular carcinoma (HCC). The aim of this study was to investigate the correlation between STAT3 activation and EMT, as well as the underlying mechanism involved in HCC progression. METHODOLOGY: We treated SMMC-7721 cells with a known STAT3 activator, epithelial growth factor (EGF); in the absence or presence of JSI-124, a selective STAT3 inhibitor. The EMT-associated morphologic and molecular changes of cells were analyzed. The EMT-mediated HCC cell invasion, migration and adhesion were evaluated. RESULTS: In this study, we found that STAT3 activation induced by EGF was associated significantly with morphologic changes, cytoskeleton rearrangement and molecular changes consistent with EMT in SMMC-7721 cells; STAT3 activation-mediated EMT may be transcriptionally induced by Twist. STAT3 activation-mediated EMT also promoted HCC cell invasion, migration and adhesion significantly. CONCLUSIONS: In summary, our study show for the first time that STAT3 activation may induce invasion and metastasis through the mediation of EMT in HCC cells. Activated STAT3 and EMT markers can serve as molecular targets for HCC treatment.

Barriers and enablers to managing obesity in general practice: a practical approach for use in implementation activities.

BACKGROUND: In 2006, the National Institute of Health and Clinical Excellence (NICE) published guidelines for the prevention and management of overweight and obesity. To tailor the implementation of guidelines, information is needed about the prevailing barriers and enablers, and practical methods for identifying barriers and enablers. AIM: To uncover and describe barriers and enablers to implementing NICE's recommendations on the management of obesity in adults in general practice, using practical qualitative methods. METHODS: A qualitative study involving semistructured interviews with seven general practitioners, seven practice nurses and nine overweight or obese patients, exploring their views and experiences on the implementation of NICE guidelines on obesity. The interviews were undertaken and analysed by a health professional with support of a health service researcher; they were recorded and transcribed verbatim and analysed using a thematic framework approach. The analysis described the reported barriers and enablers. RESULTS: Barriers included: stigma, cost of private sector services, previous patient experience, practitioners not wanting to take responsibility for obesity management, lack of consistency in care, limited practitioner skills, perceived lack of NHS services and constraints imposed by commissioners. Trust between practitioners and patients, practitioners with the skills and confidence to raise the issue of obesity, practice-based procedures and weight management services being available were perceived as enablers to implementation. CONCLUSION: This pragmatic study found that there are many barriers to the implementation of NICE guidance on obesity, involving patients, practitioners and support services for primary care.

A concept analysis of voluntary active euthanasia.

TOPIC: Euthanasia has a wide range of classifications. Confusion exists in the application of specific concepts to various studies. PURPOSE: To analyze the concept of voluntary active euthanasia using Walker and Avant's concept analysis method. SOURCES OF INFORMATION: A comprehensive literature review from various published literature and bibliographies. CONCLUSIONS: Clinical, ethical, and policy differences and similarities of euthanasia need to be debated openly, both within the medical profession and publicly. Awareness of the classifications about euthanasia may help nurses dealing with "end of life issues" properly.