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  • High mean scores were reported by the physicians for pharmacist's traditional roles such as patient counselling, assessing compliance, preventing medication errors and treating minor illnesses. Both physicians and pharmacists reported poor pharmacists practice as drug information resources despite their high perception of the importance of that role. Conclusion This study suggested that in hospitals in Egypt, there are significant differences between physicians' and pharmacists' perception and practice, and pharmacists' clinical skills are underutilized in health care.A systematic comparison framework for selecting the best retrofitting alternative for a water resource recovery facility (WRRF) is proposed in this work. The procedure is applied comparing different possible plant configurations to retrofit an existent anoxic/oxic (A/O) WRRF (Manresa, Spain) aiming to include enhanced biological phosphorus removal (EBPR). The framework for comparison was built on system analysis using a calibrated IWA ASM2d model. A multicriteria set of performance variables, as the operational and capital expenditures (OPEX and CAPEX, respectively) and robustness tests for measuring how fast the plant configuration refuses external disturbances (like ammonium and phosphate peak loads), were used for comparison. Starting from the existent WRRF, four plant configurations were tested single A2 /O (only one anoxic reactor converted to anaerobic), double A2 /O (two anoxic reactors converted to anaerobic), BARDENPHO, and UCT. The double A2 /O plant configuration was the most economical and reliable alternative for improving the existent Manresa WRRF capacity and implementing EBPR, since the effluent quality increased 3.8% compared to the current plant configuration. In addition, the double A2 /O CAPEX was close to €165,000 which was at the same order of the single A2 /O and lower than the BARDENPHO and UCT alternatives. PRACTITIONER POINTS Four configurations including EBPR were evaluated for retrofitting an A/O WRRF. A new multicriteria comparison framework was used to select the best configuration. Up to 13 criteria related to effluent quality, robustness and costs were included. A single function based on the combination of all the criteria was also evaluated.The new coronavirus SARS‐COV‐2 is currently impacting life around the globe 1. The rapid spread of this viral disease might be highly challenging for health care systems. This was seen in Northern Italy and in New York City for example2. Governments reacted with different measures such as shutdown of all schools, universities and up to a general curfew. All of those measures have a huge impact on the economy. https://www.selleckchem.com/products/lenumlostat.html The United Nations secretary general has stated recently “The COVID‐19 pandemic is one of the most dangerous challenges this world has faced in our lifetime.Aims and objectives To examine nurses' perceptions of physical and verbal violence perpetrated by patients and visitors and to investigate themes surrounding gender and the incidence of violence. Background The prevalence of violence towards nurses is a concern for nurses and hospital administrators. However, nurses who work in acute care and mental healthcare settings are particularly at high risk. This study examines the occurrence, type of violence and gender issues in a regional public hospital of Queensland Australia. Design An exploratory, qualitative design. Methods Focus group interviews with 23 nurses from Emergency Department (ED), Intensive Care Unit (ICU) and Psychiatry Department (PD) working in Queensland regional public hospital, Australia. Qualitative data were transcribed and thematically analysed manually and by NVivo. COREQ research reporting checklist followed. Results Participants reported frequent incidents of verbal and physical violence on a daily basis. Severe incidence included punching, kicking, biting and scratching, as well as threats of using weapons, such as knives. Patients were more likely to exhibit physical violence, especially towards male nurses, while hospital visitors including patient's family were more likely to exhibit verbal violence. Allocating male nurses in volatile areas and to care for violent patients raises concerns that the male nurses may be seen by their patients as "bodyguards" and not as a professional nurse. Conclusion Findings indicate that staff believe that violence is increasing, feel the burden to accept that violence as part of the job and that the bureaucratic processes of the organisation make it difficult to address violence or get support. Organisations need to be vigilant in ensuring assistance is accessible and simplified. Relevant to clinical practice This study contributes new knowledge to the discussion concerning of gender issues. Identifying gender issues could assist in developing the necessary interventions to reduce workplace violence.Objective Genetic testing for hereditary breast and ovarian cancer (HBOC) due to pathogenic variants in BRCA1 or BRCA2 is why most women present to familial cancer centers. Despite being assessed as low risk for HBOC, many women proceed with genetic testing. This study explored the genetic testing experiences of unaffected women at low risk of HBOC to clarify what motivates these women to have testing, and what are the implications of the results. Methods A qualitative approach was taken. Participants included women who had genetic testing for HBOC from 2016-2018 at the Parkville Familial Cancer Centre in Melbourne, Australia. In-depth, semi-structured interviews were conducted, and thematic analysis was undertaken on transcripts; transcripts were coded, codes were organized into a hierarchical system of categories/subcategories, and key themes were identified. Results Analysis of 19 transcripts identified five themes family underpinned all motivators for HBOC genetic testing; health professionals were influential throughout the process; participants were planning for a positive result; results influenced screening-anxiety and frequency; and negative results gave participants relief in many different ways. The three participants with positive results reported feeling shocked at the results and empowered giving this information to family members. Conclusions Women at low HBOC risk may be motivated to seek genetic testing, and access to this is increasingly offered through non-genetic health professionals. Professionals can support clients through genetic testing by recognizing familial experiences, providing accurate information, addressing risk perceptions, and understanding cancer anxiety felt by many women. This article is protected by copyright. All rights reserved.
    High mean scores were reported by the physicians for pharmacist's traditional roles such as patient counselling, assessing compliance, preventing medication errors and treating minor illnesses. Both physicians and pharmacists reported poor pharmacists practice as drug information resources despite their high perception of the importance of that role. Conclusion This study suggested that in hospitals in Egypt, there are significant differences between physicians' and pharmacists' perception and practice, and pharmacists' clinical skills are underutilized in health care.A systematic comparison framework for selecting the best retrofitting alternative for a water resource recovery facility (WRRF) is proposed in this work. The procedure is applied comparing different possible plant configurations to retrofit an existent anoxic/oxic (A/O) WRRF (Manresa, Spain) aiming to include enhanced biological phosphorus removal (EBPR). The framework for comparison was built on system analysis using a calibrated IWA ASM2d model. A multicriteria set of performance variables, as the operational and capital expenditures (OPEX and CAPEX, respectively) and robustness tests for measuring how fast the plant configuration refuses external disturbances (like ammonium and phosphate peak loads), were used for comparison. Starting from the existent WRRF, four plant configurations were tested single A2 /O (only one anoxic reactor converted to anaerobic), double A2 /O (two anoxic reactors converted to anaerobic), BARDENPHO, and UCT. The double A2 /O plant configuration was the most economical and reliable alternative for improving the existent Manresa WRRF capacity and implementing EBPR, since the effluent quality increased 3.8% compared to the current plant configuration. In addition, the double A2 /O CAPEX was close to €165,000 which was at the same order of the single A2 /O and lower than the BARDENPHO and UCT alternatives. PRACTITIONER POINTS Four configurations including EBPR were evaluated for retrofitting an A/O WRRF. A new multicriteria comparison framework was used to select the best configuration. Up to 13 criteria related to effluent quality, robustness and costs were included. A single function based on the combination of all the criteria was also evaluated.The new coronavirus SARS‐COV‐2 is currently impacting life around the globe 1. The rapid spread of this viral disease might be highly challenging for health care systems. This was seen in Northern Italy and in New York City for example2. Governments reacted with different measures such as shutdown of all schools, universities and up to a general curfew. All of those measures have a huge impact on the economy. https://www.selleckchem.com/products/lenumlostat.html The United Nations secretary general has stated recently “The COVID‐19 pandemic is one of the most dangerous challenges this world has faced in our lifetime.Aims and objectives To examine nurses' perceptions of physical and verbal violence perpetrated by patients and visitors and to investigate themes surrounding gender and the incidence of violence. Background The prevalence of violence towards nurses is a concern for nurses and hospital administrators. However, nurses who work in acute care and mental healthcare settings are particularly at high risk. This study examines the occurrence, type of violence and gender issues in a regional public hospital of Queensland Australia. Design An exploratory, qualitative design. Methods Focus group interviews with 23 nurses from Emergency Department (ED), Intensive Care Unit (ICU) and Psychiatry Department (PD) working in Queensland regional public hospital, Australia. Qualitative data were transcribed and thematically analysed manually and by NVivo. COREQ research reporting checklist followed. Results Participants reported frequent incidents of verbal and physical violence on a daily basis. Severe incidence included punching, kicking, biting and scratching, as well as threats of using weapons, such as knives. Patients were more likely to exhibit physical violence, especially towards male nurses, while hospital visitors including patient's family were more likely to exhibit verbal violence. Allocating male nurses in volatile areas and to care for violent patients raises concerns that the male nurses may be seen by their patients as "bodyguards" and not as a professional nurse. Conclusion Findings indicate that staff believe that violence is increasing, feel the burden to accept that violence as part of the job and that the bureaucratic processes of the organisation make it difficult to address violence or get support. Organisations need to be vigilant in ensuring assistance is accessible and simplified. Relevant to clinical practice This study contributes new knowledge to the discussion concerning of gender issues. Identifying gender issues could assist in developing the necessary interventions to reduce workplace violence.Objective Genetic testing for hereditary breast and ovarian cancer (HBOC) due to pathogenic variants in BRCA1 or BRCA2 is why most women present to familial cancer centers. Despite being assessed as low risk for HBOC, many women proceed with genetic testing. This study explored the genetic testing experiences of unaffected women at low risk of HBOC to clarify what motivates these women to have testing, and what are the implications of the results. Methods A qualitative approach was taken. Participants included women who had genetic testing for HBOC from 2016-2018 at the Parkville Familial Cancer Centre in Melbourne, Australia. In-depth, semi-structured interviews were conducted, and thematic analysis was undertaken on transcripts; transcripts were coded, codes were organized into a hierarchical system of categories/subcategories, and key themes were identified. Results Analysis of 19 transcripts identified five themes family underpinned all motivators for HBOC genetic testing; health professionals were influential throughout the process; participants were planning for a positive result; results influenced screening-anxiety and frequency; and negative results gave participants relief in many different ways. The three participants with positive results reported feeling shocked at the results and empowered giving this information to family members. Conclusions Women at low HBOC risk may be motivated to seek genetic testing, and access to this is increasingly offered through non-genetic health professionals. Professionals can support clients through genetic testing by recognizing familial experiences, providing accurate information, addressing risk perceptions, and understanding cancer anxiety felt by many women. This article is protected by copyright. All rights reserved.
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  • Additional roles are already being established in other services in the locality and the role merits wider discussion and testing nationally. HYPOTHESIS Capillary-dominated multiphase flow in porous materials is strongly affected by the pore walls' wettability. Recent micro-computed tomography (mCT) studies found unexpectedly wide contact angle distributions measured on static fluid distributions inside the pores. We hypothesize that analysis on time-resolved mCT data of fluid invasion events may be more directly relevant to the fluid dynamics. EXPERIMENT We approximated receding contact angles locally in time and space on time-resolved mCT datasets of drainage in a glass bead pack and a limestone. Whenever a meniscus suddenly entered one or more pores, geometric and thermodynamically consistent contact angles in the surrounding pores were measured in the time step just prior to the displacement event. We introduced a new force-based contact angle, defined to recover the measured capillary pressure in the invaded pore throat prior to interface movement. FINDINGS Unlike the classical method, the new geometric and force-based contact angles followed plausible, narrower distributions and were mutually consistent. We were unable to obtain credible results with the thermodynamically consistent method, likely because of sensitivity to common imaging artifacts and neglecting dissipation. Time-resolved mCT analysis can yield a more appropriate wettability characterization for pore scale models, despite the need to further reduce image analysis uncertainties. HYPOTHESIS The rheology of complex suspensions, such as nuclear waste slurries at the Hanford and Savannah River sites, imposes significant challenges on industrial-scale processing. Investigating the rheology and connecting it to the agglomerate morphology and underlying particle interactions in slurries will provide important fundamental knowledge, as well as prescriptive data for practical applications. Here, we use suspensions of nano-scale aluminum oxyhydroxide minerals in the form of boehmite as an analog of the radioactive waste slurry to investigate the correlation between particle interactions, agglomerate morphology, and slurry rheology. EXPERIMENTS A combination of Couette rheometry and small-angle scattering techniques (independently and simultaneously) were used to understand how agglomerate structure of slurry changes under flow and how these structural changes manifest themselves in the bulk rheology of the suspensions. FINDINGS Our experiments show that the boehmite slurries are thixotropic, with the rheology and structure of the suspensions changing with increasing exposure to flow. In the slurries, particle agglomerates begin as loose, system-spanning clusters, but exposure to moderate shear rates causes the agglomerates to irreversibly consolidate into denser clusters of finite size. The structural changes directly influence the rheological properties of the slurries such as viscosity and viscoelasticity. Our study shows that solution pH affects the amount of structural rearrangement and the kinetics of the rearrangement process, with an increase in pH leading to faster and more dramatic changes in bulk rheology, which can be understood via correlations between particle interactions and the strength of particle network. Nearly identical structural changes were also observed in Poiseuille flow geometries, implying that the observed changes are relevant in pipe flow as well. Riparian buffer systems (RBS) are considered a best management practice (BMP) in agricultural landscapes to intercept soil nitrogen (N) and phosphorus (P) leaching and surface runoff into aquatic ecosystems. However, these environmental benefits could be offset by increased greenhouse gas (GHG) emissions, including nitrous oxide (N2O). The main sources of N2O in soil are linked to processes which are mediated by soil microbial communities. These microorganisms play crucial roles in N-cycling and in the reduction of nitrate to N2, and N2O gases. This study was conducted to determine the abundance and diversity of microbial communities and functional genes associated with N-cycling and their influence on N2O emissions in different riparian land-use undisturbed natural forest (UNF), rehabilitated site (RH), grass buffer (GRB), and an adjacent agricultural land (AGR). Soil was sampled concurrently with N2O emissions on July 13, 2017. DNA was extracted and used to target key N-cycling genes for N-fixation (nifH), investigated. A synergistic effect of the activated limestone-based catalyst (LBC) and microwave irradiation on the transesterification of waste cooking oil (WCO) was screened using a two-level factorial design and response surface methodology. The catalyst was prepared using a wet-impregnation method and was characterised for its surface element, surface morphology, surface area and porosity. The reaction was performed in a purpose-built continuous microwave assisted reactor (CMAR), while the conversion and yield of biodiesel were measured using a gas chromatography. https://www.selleckchem.com/products/rgd-arg-gly-asp-peptides.html The results showed that the catalyst loading, methanol to oil molar ratio and the reaction time significantly affect the WCO conversion. The optimum conversion of oil to biodiesel up to 96.65% was achieved at catalyst loading of 5.47 wt%, methanol to oil molar ratio of 12.211 and the reaction time of 55.26 min. The application of CMAR in this work reduced the transesterification time by about 77% compared to the reaction time needed for a conventional reactor. The biodiesel produced in this work met the specification of American Society for Testing and Materials (ASTM D6751). Engine test results shows the biodiesel has a lower NOx and particulate matters emissions compared to petrodiesel. A sizeable literature has demonstrated strong negative associations between widowhood and health, but longitudinal evidence on moderating factors has been mixed. This study assesses the roles of pre-existing social capital and wealth in moderating changes in health in the event of spousal death. Samples of widowed individuals (n = 796) and matched married controls (n = 8233) are employed from 17 consecutive waves of the Household, Income and Labour Dynamics in Australia Survey (2001-2017). Individual-level fixed-effects models are used to estimate changes in physical and mental health before and after spousal death, in reference to one's own health more than two years before widowhood. Results show a temporary physical health improvement in the year of spousal death, and a decline in mental health beginning up to two years before spousal death, lasting up to two years after spousal death. Using social capital-from children, club membership or volunteering status, and social connections-observed earlier than two years before spousal death, this study finds that widowed individuals with higher social capital show poorer mental health than those with less capital.
    Additional roles are already being established in other services in the locality and the role merits wider discussion and testing nationally. HYPOTHESIS Capillary-dominated multiphase flow in porous materials is strongly affected by the pore walls' wettability. Recent micro-computed tomography (mCT) studies found unexpectedly wide contact angle distributions measured on static fluid distributions inside the pores. We hypothesize that analysis on time-resolved mCT data of fluid invasion events may be more directly relevant to the fluid dynamics. EXPERIMENT We approximated receding contact angles locally in time and space on time-resolved mCT datasets of drainage in a glass bead pack and a limestone. Whenever a meniscus suddenly entered one or more pores, geometric and thermodynamically consistent contact angles in the surrounding pores were measured in the time step just prior to the displacement event. We introduced a new force-based contact angle, defined to recover the measured capillary pressure in the invaded pore throat prior to interface movement. FINDINGS Unlike the classical method, the new geometric and force-based contact angles followed plausible, narrower distributions and were mutually consistent. We were unable to obtain credible results with the thermodynamically consistent method, likely because of sensitivity to common imaging artifacts and neglecting dissipation. Time-resolved mCT analysis can yield a more appropriate wettability characterization for pore scale models, despite the need to further reduce image analysis uncertainties. HYPOTHESIS The rheology of complex suspensions, such as nuclear waste slurries at the Hanford and Savannah River sites, imposes significant challenges on industrial-scale processing. Investigating the rheology and connecting it to the agglomerate morphology and underlying particle interactions in slurries will provide important fundamental knowledge, as well as prescriptive data for practical applications. Here, we use suspensions of nano-scale aluminum oxyhydroxide minerals in the form of boehmite as an analog of the radioactive waste slurry to investigate the correlation between particle interactions, agglomerate morphology, and slurry rheology. EXPERIMENTS A combination of Couette rheometry and small-angle scattering techniques (independently and simultaneously) were used to understand how agglomerate structure of slurry changes under flow and how these structural changes manifest themselves in the bulk rheology of the suspensions. FINDINGS Our experiments show that the boehmite slurries are thixotropic, with the rheology and structure of the suspensions changing with increasing exposure to flow. In the slurries, particle agglomerates begin as loose, system-spanning clusters, but exposure to moderate shear rates causes the agglomerates to irreversibly consolidate into denser clusters of finite size. The structural changes directly influence the rheological properties of the slurries such as viscosity and viscoelasticity. Our study shows that solution pH affects the amount of structural rearrangement and the kinetics of the rearrangement process, with an increase in pH leading to faster and more dramatic changes in bulk rheology, which can be understood via correlations between particle interactions and the strength of particle network. Nearly identical structural changes were also observed in Poiseuille flow geometries, implying that the observed changes are relevant in pipe flow as well. Riparian buffer systems (RBS) are considered a best management practice (BMP) in agricultural landscapes to intercept soil nitrogen (N) and phosphorus (P) leaching and surface runoff into aquatic ecosystems. However, these environmental benefits could be offset by increased greenhouse gas (GHG) emissions, including nitrous oxide (N2O). The main sources of N2O in soil are linked to processes which are mediated by soil microbial communities. These microorganisms play crucial roles in N-cycling and in the reduction of nitrate to N2, and N2O gases. This study was conducted to determine the abundance and diversity of microbial communities and functional genes associated with N-cycling and their influence on N2O emissions in different riparian land-use undisturbed natural forest (UNF), rehabilitated site (RH), grass buffer (GRB), and an adjacent agricultural land (AGR). Soil was sampled concurrently with N2O emissions on July 13, 2017. DNA was extracted and used to target key N-cycling genes for N-fixation (nifH), investigated. A synergistic effect of the activated limestone-based catalyst (LBC) and microwave irradiation on the transesterification of waste cooking oil (WCO) was screened using a two-level factorial design and response surface methodology. The catalyst was prepared using a wet-impregnation method and was characterised for its surface element, surface morphology, surface area and porosity. The reaction was performed in a purpose-built continuous microwave assisted reactor (CMAR), while the conversion and yield of biodiesel were measured using a gas chromatography. https://www.selleckchem.com/products/rgd-arg-gly-asp-peptides.html The results showed that the catalyst loading, methanol to oil molar ratio and the reaction time significantly affect the WCO conversion. The optimum conversion of oil to biodiesel up to 96.65% was achieved at catalyst loading of 5.47 wt%, methanol to oil molar ratio of 12.211 and the reaction time of 55.26 min. The application of CMAR in this work reduced the transesterification time by about 77% compared to the reaction time needed for a conventional reactor. The biodiesel produced in this work met the specification of American Society for Testing and Materials (ASTM D6751). Engine test results shows the biodiesel has a lower NOx and particulate matters emissions compared to petrodiesel. A sizeable literature has demonstrated strong negative associations between widowhood and health, but longitudinal evidence on moderating factors has been mixed. This study assesses the roles of pre-existing social capital and wealth in moderating changes in health in the event of spousal death. Samples of widowed individuals (n = 796) and matched married controls (n = 8233) are employed from 17 consecutive waves of the Household, Income and Labour Dynamics in Australia Survey (2001-2017). Individual-level fixed-effects models are used to estimate changes in physical and mental health before and after spousal death, in reference to one's own health more than two years before widowhood. Results show a temporary physical health improvement in the year of spousal death, and a decline in mental health beginning up to two years before spousal death, lasting up to two years after spousal death. Using social capital-from children, club membership or volunteering status, and social connections-observed earlier than two years before spousal death, this study finds that widowed individuals with higher social capital show poorer mental health than those with less capital.
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  • Furthermore, H2 positively modulated β-catenin in H2O2-treated melanocytes, and the β-catenin pathway was implicated in H2-induced Nrf2 activation. Collectively, our results indicate that H2 could be a promising therapeutic agent for vitiligo treatment via attenuating oxidative damage, and its beneficial effect in human melanocytes might involve Wnt/β-catenin-mediated activation of Nrf2 signaling. Itch, initiated by the activation of sensory neurons, is frequently associated with dermatological diseases. MrgprA3+ sensory neurons have been identified as one of the major itch-sensing neuronal populations. Mounting evidence has demonstrated that peripheral pathological conditions induce physiological regulations of sensory neurons, which is critical for the maintenance of chronic itch sensation. However, the underlying molecular mechanisms are not clear. Here we performed RNA sequencing of genetically labeled MrgprA3+ neurons under both naïve and allergic contact dermatitis conditions. Our results revealed the unique molecular signature of itch-sensing neurons and the distinct transcriptional profile changes that result in response to dermatitis. We found enrichment of nine Mrgpr family members and two histamine receptors in MrgprA3+ neurons, suggesting that MrgprA3+ neurons are a direct neuronal target for histamine and Mrgprs agonists. In addition, Ptpn6 and Pcdh12 were identified as highly selective markers of MrgprA3+ neurons. We also discovered that MrgprA3+ neurons respond to skin dermatitis in a way that is unique from other sensory neurons by regulating a combination of transcriptional factors, ion channels, and key molecules involved in synaptic transmission. These results significantly increase our knowledge of itch transmission and uncover potential targets for combating itch. Hepatocellular carcinoma (HCC) remains a major clinical challenge. Although mitophagy is implicated in hepatocarcinogenesis, novel therapeutic options targeting mitophagy for HCC treatment still await further studies. Here, we demonstrate that sanguinarine induces cell death in HCC cell line ****-97H through the mitochondrial apoptosis pathway. Sanguinarine triggers mitochondrial dysfunction and PTEN-induced putative kinase 1 (PINK1)/Parkin upregulation and recruitment to mitochondria. Elevated levels of p62 and LC3-II/I ratios suggest that sanguinarine is both an inducer of autophagy and a blocker of autolysosome formation, which is further confirmed by LC3-II conversion levels in presence of autophagy and mitophagy inhibitors, as well as an autophagy activator. In addition, blocking autophagy promotes sanguinarine-induced cell death, indicating mitophagy plays a cytoprotective role in sanguinarine-treated cells. Our findings suggest that blocking mitophagy may contribute to sanguinarine-induced mitochondrial apoptosis through the prevention of damaged mitochondrial clearance. BACKGROUND PTEN is a tumour suppressor gene that has been proven to be related to breast cancer incidence and tumour progression. The aim of this study was to investigate the frequency of PTEN mutations in breast carcinomas in China and the relationships of PTEN mutations with clinicopathological parameters and clinical outcomes. MATERIAL AND METHODS Trimmomatic, Burrows-Wheeler Aligner (BWA), ANNOVAR, SAMtools, and Sanger sequencing were used to analyse PTEN mutations and identify variants in Chinese breast cancer. The frequency of PTEN mutations and the relationships of PTEN mutations with clinicopathological parameters and clinical outcomes were evaluated in breast carcinomas in China. RESULTS The rate of PTEN germline mutation was 0.23% (n = 9) among 3955 unselected primary breast cancer patients. Of these 9 patients, 2 carried pathogenic mutations, and both were identified as having infiltrative carcinoma. One patient had a family history. The other 7 patients carried only PTEN germline variants that were not identified as pathogenic mutations. CONCLUSIONS We studied the frequency of PTEN germline mutations in a sequential cohort of Chinese breast carcinoma patients. https://www.selleckchem.com/products/Perifosine.html Based on these data, we hypothesize that the germline mutation of the PTEN gene is not closely related to the occurrence of breast cancer in the Chinese population. In the clinic, the PTEN germline mutation cannot be used as the basis for the detection of breast cancer. V.MiR-155 is an immune microRNA encoded within the ****gene. Dozens of researches have uncovered the importance of high expression of miR-155 in promoting the development of immune organs and strengthening immune response and inflammatory response. Some natural mutations located in the miR-155/****region were revealed to disturb the expression level of miR-155 in several mammalian species, and our previous study also identified several mutations occurring near the miR-155/****region in pigs. However, the consequences of ****locus-harbored mutations in pig genome remain unclear. In this study, we used Chinese Meishan and British Large White pigs to identify mutations within the miR-155/****region, and explore whether there are effects on expressions of miR-155 and its target genes. Target sequencing identified six potential FOXP3 protein binding sites (AAACA) in the ****gene, among which there were two A/C mutations (AAACC) at the -108 bp and -305 bp upstream of the miR-155 precursors in Meishan pigs, but not in Large White pigs. A series of experiments confirmed that the FOXP3 protein mainly binds to the -305 bp position, and the binding efficiency of the CC haplotype to FOXP3 protein was higher than that of the wild type, resulting in increased expression of miR-155, and consequentially decreased the expressions of its target genes. Our newly identified mutations are functional, which explain partial reasons for the difference in immunity between Meishan and Large White pigs, and provide potential molecular markers to genetically improve the disease resistance in the pig breeding practice. BACKGROUND The 2019 novel coronavirus (SARS-CoV-2) is a new human coronavirus which is spreading with epidemic features in China and other Asian countries with cases reported worldwide. This novel Coronavirus Disease (COVID-19) is associated with a respiratory illness that may cause severe pneumonia and acute respiratory distress syndrome (ARDS). Although related to the Severe Acute Respiratory Syndrome (SARS) and the Middle East Respiratory Syndrome (MERS), COVID-19 shows some peculiar pathogenetic, epidemiological and clinical features which have not been completely understood to date. OBJECTIVES We provide a review of the differences in terms of pathogenesis, epidemiology and clinical features between COVID-19, SARS and MERS. SOURCES The most recent literature in English language regarding COVID-19 has been reviewed and extracted data have been compared with the current scientific evidence about SARS and MERS epidemics. CONTENT COVID-19 seems not to be very different from SARS regarding its clinical features.
    Furthermore, H2 positively modulated β-catenin in H2O2-treated melanocytes, and the β-catenin pathway was implicated in H2-induced Nrf2 activation. Collectively, our results indicate that H2 could be a promising therapeutic agent for vitiligo treatment via attenuating oxidative damage, and its beneficial effect in human melanocytes might involve Wnt/β-catenin-mediated activation of Nrf2 signaling. Itch, initiated by the activation of sensory neurons, is frequently associated with dermatological diseases. MrgprA3+ sensory neurons have been identified as one of the major itch-sensing neuronal populations. Mounting evidence has demonstrated that peripheral pathological conditions induce physiological regulations of sensory neurons, which is critical for the maintenance of chronic itch sensation. However, the underlying molecular mechanisms are not clear. Here we performed RNA sequencing of genetically labeled MrgprA3+ neurons under both naïve and allergic contact dermatitis conditions. Our results revealed the unique molecular signature of itch-sensing neurons and the distinct transcriptional profile changes that result in response to dermatitis. We found enrichment of nine Mrgpr family members and two histamine receptors in MrgprA3+ neurons, suggesting that MrgprA3+ neurons are a direct neuronal target for histamine and Mrgprs agonists. In addition, Ptpn6 and Pcdh12 were identified as highly selective markers of MrgprA3+ neurons. We also discovered that MrgprA3+ neurons respond to skin dermatitis in a way that is unique from other sensory neurons by regulating a combination of transcriptional factors, ion channels, and key molecules involved in synaptic transmission. These results significantly increase our knowledge of itch transmission and uncover potential targets for combating itch. Hepatocellular carcinoma (HCC) remains a major clinical challenge. Although mitophagy is implicated in hepatocarcinogenesis, novel therapeutic options targeting mitophagy for HCC treatment still await further studies. Here, we demonstrate that sanguinarine induces cell death in HCC cell line MHCC-97H through the mitochondrial apoptosis pathway. Sanguinarine triggers mitochondrial dysfunction and PTEN-induced putative kinase 1 (PINK1)/Parkin upregulation and recruitment to mitochondria. Elevated levels of p62 and LC3-II/I ratios suggest that sanguinarine is both an inducer of autophagy and a blocker of autolysosome formation, which is further confirmed by LC3-II conversion levels in presence of autophagy and mitophagy inhibitors, as well as an autophagy activator. In addition, blocking autophagy promotes sanguinarine-induced cell death, indicating mitophagy plays a cytoprotective role in sanguinarine-treated cells. Our findings suggest that blocking mitophagy may contribute to sanguinarine-induced mitochondrial apoptosis through the prevention of damaged mitochondrial clearance. BACKGROUND PTEN is a tumour suppressor gene that has been proven to be related to breast cancer incidence and tumour progression. The aim of this study was to investigate the frequency of PTEN mutations in breast carcinomas in China and the relationships of PTEN mutations with clinicopathological parameters and clinical outcomes. MATERIAL AND METHODS Trimmomatic, Burrows-Wheeler Aligner (BWA), ANNOVAR, SAMtools, and Sanger sequencing were used to analyse PTEN mutations and identify variants in Chinese breast cancer. The frequency of PTEN mutations and the relationships of PTEN mutations with clinicopathological parameters and clinical outcomes were evaluated in breast carcinomas in China. RESULTS The rate of PTEN germline mutation was 0.23% (n = 9) among 3955 unselected primary breast cancer patients. Of these 9 patients, 2 carried pathogenic mutations, and both were identified as having infiltrative carcinoma. One patient had a family history. The other 7 patients carried only PTEN germline variants that were not identified as pathogenic mutations. CONCLUSIONS We studied the frequency of PTEN germline mutations in a sequential cohort of Chinese breast carcinoma patients. https://www.selleckchem.com/products/Perifosine.html Based on these data, we hypothesize that the germline mutation of the PTEN gene is not closely related to the occurrence of breast cancer in the Chinese population. In the clinic, the PTEN germline mutation cannot be used as the basis for the detection of breast cancer. V.MiR-155 is an immune microRNA encoded within the BIC gene. Dozens of researches have uncovered the importance of high expression of miR-155 in promoting the development of immune organs and strengthening immune response and inflammatory response. Some natural mutations located in the miR-155/BIC region were revealed to disturb the expression level of miR-155 in several mammalian species, and our previous study also identified several mutations occurring near the miR-155/BIC region in pigs. However, the consequences of BIC locus-harbored mutations in pig genome remain unclear. In this study, we used Chinese Meishan and British Large White pigs to identify mutations within the miR-155/BIC region, and explore whether there are effects on expressions of miR-155 and its target genes. Target sequencing identified six potential FOXP3 protein binding sites (AAACA) in the BIC gene, among which there were two A/C mutations (AAACC) at the -108 bp and -305 bp upstream of the miR-155 precursors in Meishan pigs, but not in Large White pigs. A series of experiments confirmed that the FOXP3 protein mainly binds to the -305 bp position, and the binding efficiency of the CC haplotype to FOXP3 protein was higher than that of the wild type, resulting in increased expression of miR-155, and consequentially decreased the expressions of its target genes. Our newly identified mutations are functional, which explain partial reasons for the difference in immunity between Meishan and Large White pigs, and provide potential molecular markers to genetically improve the disease resistance in the pig breeding practice. BACKGROUND The 2019 novel coronavirus (SARS-CoV-2) is a new human coronavirus which is spreading with epidemic features in China and other Asian countries with cases reported worldwide. This novel Coronavirus Disease (COVID-19) is associated with a respiratory illness that may cause severe pneumonia and acute respiratory distress syndrome (ARDS). Although related to the Severe Acute Respiratory Syndrome (SARS) and the Middle East Respiratory Syndrome (MERS), COVID-19 shows some peculiar pathogenetic, epidemiological and clinical features which have not been completely understood to date. OBJECTIVES We provide a review of the differences in terms of pathogenesis, epidemiology and clinical features between COVID-19, SARS and MERS. SOURCES The most recent literature in English language regarding COVID-19 has been reviewed and extracted data have been compared with the current scientific evidence about SARS and MERS epidemics. CONTENT COVID-19 seems not to be very different from SARS regarding its clinical features.
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  • We have studied nano-patterning of a two-dimensional material with ultrafine helium ion beam in the aspect of shape-, size- and damage-control. It reveals that the crystalline structure plays an important role in the shape-control. Instead of commonly circular-shaped nanopore, a spot irradiation onto a single layer of molybdenum disulfide (MoS2) gives rise to a rhombus-shaped nanopore, which is well explained by the sub-rhombus crystalline structure of MoS2. Helium ion beam also shows a promising capability of precisely controlling the size by a delivered dose. https://www.selleckchem.com/products/Puromycin-2HCl.html However, the size of the nanopores is not linear with the delivered dose, due to Gaussian distributed intensity profile of helium ion beam. The intensity profiles are further estimated by considering aperture size, those results could be taken as a significant reference for size-control. In addition, we clarify that most of the damage is a result of re-deposition, thus controlling re-deposition might be a useful way to alleviate the damage. © 2020 IOP Publishing Ltd.Light absorption generates strongly bound excitons in organic solar cells (OSCs). To obtain efficient charge generation, a large driving force is required, which causes a large energy loss (Eloss) and severely hinders the improvement in the power conversion efficiencies (PCEs) of OSCs. Recently, the development of non-fullerene OSCs has seen great success, and the resulting OSCs can yield highly efficient charge generation with a negligible driving force, which raises a fundamental question about how the excitons split into free charges. From a chemical structure perspective, the molecular electrostatic potential differences between donors and acceptors may play a critical role in facilitating charge separation. Although the Eloss caused by charge generation has been suppressed, charge recombination, particularly via non-radiative pathways, severely limits further improvements in the PCEs. In OSCs with negligible driving forces, the lowest excited state, a hybrid local exciton-charge transfer state, is believed to have a strong association with the non-radiative Eloss. This review discusses the efficient charge generation at low Eloss values in highly efficient OSCs and highlights the issues that should be tackled to further improve the PCEs to new levels (~ 20%). © 2020 IOP Publishing Ltd.OBJECTIVE Retinal prostheses aim to restore vision in patients with retinal degenerative diseases, such as age-related macular degeneration and retinitis pigmentosa. By implanting an array of microelectrodes, such a device creates percepts in patients through electrical stimulation of surviving retinal neurons. A challenge for retinal prostheses when trying to return high quality vision is the unintended activation of retinal ganglion cells through the stimulation of passing axon bundles, which leads to patients reporting large, elongated patches of light instead of focal spots. APPROACH In this work, we used calcium imaging to record the responses of retinal ganglion cells to electrical stimulation in explanted retina using rectangular electrodes placed with different orientations relative to the axon bundles. MAIN RESULTS We showed that narrow, rectangular electrodes oriented parallel to the axon bundles can achieve focal stimulation. To further improve the strategy, we studied the impact of different stimulation waveforms and electrode configurations. We found the selectivity for focal stimulation to be higher when using short (33 µs), anodic-first biphasic pulses, with long electrode lengths and at least 50µm electrode-to-retinal separation. Focal stimulation was, in fact, less selective when the electrodes made direct contact with the retinal surface due to unwanted preferential stimulation of the proximal axon bundles. SIGNIFICANCE When employed in retinal prostheses, the proposed stimulation strategy is expected to provide improved quality of vision to the blind. © 2020 IOP Publishing Ltd.Osteoporosis is a metabolic disease that affects bone tissue and is highly associated with bone fractures. Typical osteoporosis fracture treatments, such as bisphosphonates and hormone replacement, present important challenges because of their low bioavailability on the site of action. Options to overcome this issue are systems for the local release of therapeutic agents such as bioactive glasses containing therapeutic molecules and ions. These agents are released during the dissolution process, combining the drugs and ion therapeutic effects for osteoporosis treatment. Among the therapeutic agents that can be applied for bone repair are strontium ion and phytopharmaceutical icariin, which have shown potential to promote healthy bone marrow stem cells osteogenic differentiation, increase bone formation and prevent bone loss. Submicron Sr-containing bioactive glass mesoporous spheres with sustained ion release capacity were obtained. Icariin was successfully incorporated into the particles, and the glass composition influenced the icariin incorporation efficiency and release rates. In this work, for the first time, Sr and icariin were incorporated into bioactive glass submicron mesoporous spheres and the in vitro effects of the therapeutic agents release were evaluated on the reduced osteogenic potential of rat osteoporotic bone marrow mesenchymal stem cells, and results showed an improvement on the reduced differentiation potential. © 2020 IOP Publishing Ltd.N-doped carbon-based materials are crucial electrically conductive additives and non-metal electrocatalysts for oxygen reduction reaction. At present, many researches are focused on the effects of micropore, mesopore and hierarchical pore structure on the catalytic activity, however, there are few works concerning the role of large-dimension through-hole structure. Hence, in this work, we prepare two kinds of carbon materials with large through-hole structure, i.e. N-doped carbon hollow-spheres and hollow-tubes, as the oxygen reduction catalysts. The synthesis follows template-free morphology-controlled pyrolysis, which is more convenient than the preparation of conventional N-doped nanotubes and graphene. The resultant N-doped carbon hollow-spheres and hollow-tubes exhibit evidently enhanced ORR catalytic activity, remarkable long-term stability and methanol resistance. The large-dimension through-hole structure is found to account for the increase in mass transfer. © 2020 IOP Publishing Ltd.
    We have studied nano-patterning of a two-dimensional material with ultrafine helium ion beam in the aspect of shape-, size- and damage-control. It reveals that the crystalline structure plays an important role in the shape-control. Instead of commonly circular-shaped nanopore, a spot irradiation onto a single layer of molybdenum disulfide (MoS2) gives rise to a rhombus-shaped nanopore, which is well explained by the sub-rhombus crystalline structure of MoS2. Helium ion beam also shows a promising capability of precisely controlling the size by a delivered dose. https://www.selleckchem.com/products/Puromycin-2HCl.html However, the size of the nanopores is not linear with the delivered dose, due to Gaussian distributed intensity profile of helium ion beam. The intensity profiles are further estimated by considering aperture size, those results could be taken as a significant reference for size-control. In addition, we clarify that most of the damage is a result of re-deposition, thus controlling re-deposition might be a useful way to alleviate the damage. © 2020 IOP Publishing Ltd.Light absorption generates strongly bound excitons in organic solar cells (OSCs). To obtain efficient charge generation, a large driving force is required, which causes a large energy loss (Eloss) and severely hinders the improvement in the power conversion efficiencies (PCEs) of OSCs. Recently, the development of non-fullerene OSCs has seen great success, and the resulting OSCs can yield highly efficient charge generation with a negligible driving force, which raises a fundamental question about how the excitons split into free charges. From a chemical structure perspective, the molecular electrostatic potential differences between donors and acceptors may play a critical role in facilitating charge separation. Although the Eloss caused by charge generation has been suppressed, charge recombination, particularly via non-radiative pathways, severely limits further improvements in the PCEs. In OSCs with negligible driving forces, the lowest excited state, a hybrid local exciton-charge transfer state, is believed to have a strong association with the non-radiative Eloss. This review discusses the efficient charge generation at low Eloss values in highly efficient OSCs and highlights the issues that should be tackled to further improve the PCEs to new levels (~ 20%). © 2020 IOP Publishing Ltd.OBJECTIVE Retinal prostheses aim to restore vision in patients with retinal degenerative diseases, such as age-related macular degeneration and retinitis pigmentosa. By implanting an array of microelectrodes, such a device creates percepts in patients through electrical stimulation of surviving retinal neurons. A challenge for retinal prostheses when trying to return high quality vision is the unintended activation of retinal ganglion cells through the stimulation of passing axon bundles, which leads to patients reporting large, elongated patches of light instead of focal spots. APPROACH In this work, we used calcium imaging to record the responses of retinal ganglion cells to electrical stimulation in explanted retina using rectangular electrodes placed with different orientations relative to the axon bundles. MAIN RESULTS We showed that narrow, rectangular electrodes oriented parallel to the axon bundles can achieve focal stimulation. To further improve the strategy, we studied the impact of different stimulation waveforms and electrode configurations. We found the selectivity for focal stimulation to be higher when using short (33 µs), anodic-first biphasic pulses, with long electrode lengths and at least 50µm electrode-to-retinal separation. Focal stimulation was, in fact, less selective when the electrodes made direct contact with the retinal surface due to unwanted preferential stimulation of the proximal axon bundles. SIGNIFICANCE When employed in retinal prostheses, the proposed stimulation strategy is expected to provide improved quality of vision to the blind. © 2020 IOP Publishing Ltd.Osteoporosis is a metabolic disease that affects bone tissue and is highly associated with bone fractures. Typical osteoporosis fracture treatments, such as bisphosphonates and hormone replacement, present important challenges because of their low bioavailability on the site of action. Options to overcome this issue are systems for the local release of therapeutic agents such as bioactive glasses containing therapeutic molecules and ions. These agents are released during the dissolution process, combining the drugs and ion therapeutic effects for osteoporosis treatment. Among the therapeutic agents that can be applied for bone repair are strontium ion and phytopharmaceutical icariin, which have shown potential to promote healthy bone marrow stem cells osteogenic differentiation, increase bone formation and prevent bone loss. Submicron Sr-containing bioactive glass mesoporous spheres with sustained ion release capacity were obtained. Icariin was successfully incorporated into the particles, and the glass composition influenced the icariin incorporation efficiency and release rates. In this work, for the first time, Sr and icariin were incorporated into bioactive glass submicron mesoporous spheres and the in vitro effects of the therapeutic agents release were evaluated on the reduced osteogenic potential of rat osteoporotic bone marrow mesenchymal stem cells, and results showed an improvement on the reduced differentiation potential. © 2020 IOP Publishing Ltd.N-doped carbon-based materials are crucial electrically conductive additives and non-metal electrocatalysts for oxygen reduction reaction. At present, many researches are focused on the effects of micropore, mesopore and hierarchical pore structure on the catalytic activity, however, there are few works concerning the role of large-dimension through-hole structure. Hence, in this work, we prepare two kinds of carbon materials with large through-hole structure, i.e. N-doped carbon hollow-spheres and hollow-tubes, as the oxygen reduction catalysts. The synthesis follows template-free morphology-controlled pyrolysis, which is more convenient than the preparation of conventional N-doped nanotubes and graphene. The resultant N-doped carbon hollow-spheres and hollow-tubes exhibit evidently enhanced ORR catalytic activity, remarkable long-term stability and methanol resistance. The large-dimension through-hole structure is found to account for the increase in mass transfer. © 2020 IOP Publishing Ltd.
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  • These findings provide useful insights into the development of potent inhibitors for targeting Nef protein functions. This article is protected by copyright. All rights reserved.Aims and objectives This study aimed to comparatively evaluate the psychometric quality of two single-item pain-intensity measures the Numeric Rating Scale (NRS) and the Verbal Rating Scale (VRS). Background Measuring pain intensity is a vital step in initiating symptom management and evaluating the effectiveness of interventions with cancer patients. Single-item pain-intensity measures of the NRS and VRS format have been evaluated to be acceptable for use in clinical practice and research; however, evidence to choose one over the other, as a standardized pain-assessment format, is insufficient. Design Descriptive correlational study. The study was guided and reported following the STROBE guideline. Methods Data accrued at two time points during cancer treatment with a total of 249 patients treated in a Korean University Hospital. Two single-item measures were constructed to assess pain intensity over 1 week. The Brief Pain Inventory (BPI; pain intensity subscale and interference subscale) and the functional measure to assess global pain intensity over the past week.Recently, a novel group of spindle cell tumors defined by S100 and CD34 co-expression harboring recurrent fusions involving RET, RAF1, BRAF, and NTRK1/2 gene has been identified. Morphologically, they are characterized by monomorphic neoplasm cells, "patternless" growth pattern, stromal and perivascular hyalinization, lacked necrosis. We reported a 52-year-old Chinese female patient with a S100 and CD34 co-expression sarcoma presenting in the right proximal forearm. The forearm mass initially emerged 19 months ago when it was misdiagnosed as a solitary fibrous tumor and was surgically removed without further treatment. Microscopically, the primary and the recurred tumors share the same features, resembling the morphology of the recently characterized group. Nevertheless, some distinct features, such as predominantly epithelioid tumor cells and focally staghorn vessels, were also present in our case. Genomic profiling with clinical next-generation sequencing was performed and revealed CDC42SE2-BRAF gene fusion, MET amplification, and CDKN2A/B deletion. Both FISH and nested RT-PCR were performed to confirm the gene fusion. The patient was treated with crizotinib for two cycles but showed no obvious benefit. The presented case adds to the spectrum of the novel, characterized solid tumors, and provides suggestions for emerging therapeutic strategies for precision medicine involving targeted kinase inhibitors. This article is protected by copyright. All rights reserved.Intracardiac blood cysts are rare congenital malformations most commonly located in the endocardium of semilunar or atrioventricular valves. They are predominantly seen in infants, especially below 2 months of age, and disappear spontaneously in the first 6 months of life making the detection of blood cysts a rare finding in the adult population. Although most patients are asymptomatic, they may occasionally present with obstruction, valvular dysfunction, or embolism. Herein, we present a 2.5-year-old female patient, who was successfully treated with surgical excision of an intracardiac blood cyst causing mild-to-moderate mitral regurgitation and obstruction.Safety in health care settings is a multidimensional construct involving factors such as patient safety, occupational safety and quality improvement, all designed to protect hospital staff and the public. Traditionally, harms in hospital care were most commonly associated with errors in medication administration and poor staffing levels, however, recently aggression and violence in hospital settings has become a significant challenge to the maintenance of patient and staff safety (Hahn et al., 2015).Multiple myeloma is a clonal malignancy of plasma cells in the bone marrow. Risk stratification is partly based on cytogenetic findings that include abnormalities of the IGH locus as determined by fluorescence in situ hybridization (FISH), such as rearrangements that result in either standard-risk or high-risk gene fusions. IGH deletions have been evaluated as a group in multiple myeloma patients with respect to cumulative outcomes but have provided limited guidance. Whether these deletions have the potential to result in gene fusions and thus further stratify patients is unknown. We identified 229 IGH deletions in patients referred for plasma cell dyscrasia genetic testing over 5.5 years. Follow-up was conducted on 208 of the deletions with dual fusion FISH probes for standard-risk (IGH-CCND1) and high-risk IGH gene fusions (IGH-FGFR3, IGH-MAF, IGH-MAFB). https://www.selleckchem.com/products/afuresertib-gsk2110183.html Of all deletions identified with follow-up, 44 (21%) resulted in a gene fusion as detected by FISH, 15 (7%) of which were fusion partners associated with high-risk multiple myeloma. All fusion-positive 3'-IGH deletions (6 fusions) resulted in high-risk IGH-FGFR3 fusions. Of the 15 high-risk fusion-positive cases, eight were without other high-risk cytogenetic findings. This study is the first to evaluate the presence of IGH gene fusions upon identification of IGH deletions and to characterize the deletion locus. Importantly, these findings indicate that follow-up FISH studies with dual fusion probes should be standard of care when IGH deletions are identified in multiple myeloma. This article is protected by copyright. All rights reserved.Background Our main objective was to review the literature to answer the following questions regarding pediatric massive transfusion (PMT) protocols 1) How is PMT defined? 2) Which blood product ratios have been investigated and what is their effect on outcomes? 3) What evidence exists regarding PMT outcomes? Methods The PRISMA guidelines were used. We searched PubMed, Google Scholar, Cochrane Library, EMBASE, Wiley Online Library, and Ovid. Articles were screened for inclusion based on relevance to PMT. Articles were assessed for study design, presence of established/tested PMT, PMT definition, PMT activation criteria, and Transfusion Ratios, for final determination of article inclusion. Results Our search produced 3213 articles with 33 included for final review. Existing definitions of PMT are based on volume administered/kg but vary in timeframe criteria (over 4 hr vs 24 hr). Some studies have investigated "high" balanced transfusion ratios as seen in adults (11 FFPpRBC) with a few showing statistically significant improvement in pediatric mortality vs lower ratios.
    These findings provide useful insights into the development of potent inhibitors for targeting Nef protein functions. This article is protected by copyright. All rights reserved.Aims and objectives This study aimed to comparatively evaluate the psychometric quality of two single-item pain-intensity measures the Numeric Rating Scale (NRS) and the Verbal Rating Scale (VRS). Background Measuring pain intensity is a vital step in initiating symptom management and evaluating the effectiveness of interventions with cancer patients. Single-item pain-intensity measures of the NRS and VRS format have been evaluated to be acceptable for use in clinical practice and research; however, evidence to choose one over the other, as a standardized pain-assessment format, is insufficient. Design Descriptive correlational study. The study was guided and reported following the STROBE guideline. Methods Data accrued at two time points during cancer treatment with a total of 249 patients treated in a Korean University Hospital. Two single-item measures were constructed to assess pain intensity over 1 week. The Brief Pain Inventory (BPI; pain intensity subscale and interference subscale) and the functional measure to assess global pain intensity over the past week.Recently, a novel group of spindle cell tumors defined by S100 and CD34 co-expression harboring recurrent fusions involving RET, RAF1, BRAF, and NTRK1/2 gene has been identified. Morphologically, they are characterized by monomorphic neoplasm cells, "patternless" growth pattern, stromal and perivascular hyalinization, lacked necrosis. We reported a 52-year-old Chinese female patient with a S100 and CD34 co-expression sarcoma presenting in the right proximal forearm. The forearm mass initially emerged 19 months ago when it was misdiagnosed as a solitary fibrous tumor and was surgically removed without further treatment. Microscopically, the primary and the recurred tumors share the same features, resembling the morphology of the recently characterized group. Nevertheless, some distinct features, such as predominantly epithelioid tumor cells and focally staghorn vessels, were also present in our case. Genomic profiling with clinical next-generation sequencing was performed and revealed CDC42SE2-BRAF gene fusion, MET amplification, and CDKN2A/B deletion. Both FISH and nested RT-PCR were performed to confirm the gene fusion. The patient was treated with crizotinib for two cycles but showed no obvious benefit. The presented case adds to the spectrum of the novel, characterized solid tumors, and provides suggestions for emerging therapeutic strategies for precision medicine involving targeted kinase inhibitors. This article is protected by copyright. All rights reserved.Intracardiac blood cysts are rare congenital malformations most commonly located in the endocardium of semilunar or atrioventricular valves. They are predominantly seen in infants, especially below 2 months of age, and disappear spontaneously in the first 6 months of life making the detection of blood cysts a rare finding in the adult population. Although most patients are asymptomatic, they may occasionally present with obstruction, valvular dysfunction, or embolism. Herein, we present a 2.5-year-old female patient, who was successfully treated with surgical excision of an intracardiac blood cyst causing mild-to-moderate mitral regurgitation and obstruction.Safety in health care settings is a multidimensional construct involving factors such as patient safety, occupational safety and quality improvement, all designed to protect hospital staff and the public. Traditionally, harms in hospital care were most commonly associated with errors in medication administration and poor staffing levels, however, recently aggression and violence in hospital settings has become a significant challenge to the maintenance of patient and staff safety (Hahn et al., 2015).Multiple myeloma is a clonal malignancy of plasma cells in the bone marrow. Risk stratification is partly based on cytogenetic findings that include abnormalities of the IGH locus as determined by fluorescence in situ hybridization (FISH), such as rearrangements that result in either standard-risk or high-risk gene fusions. IGH deletions have been evaluated as a group in multiple myeloma patients with respect to cumulative outcomes but have provided limited guidance. Whether these deletions have the potential to result in gene fusions and thus further stratify patients is unknown. We identified 229 IGH deletions in patients referred for plasma cell dyscrasia genetic testing over 5.5 years. Follow-up was conducted on 208 of the deletions with dual fusion FISH probes for standard-risk (IGH-CCND1) and high-risk IGH gene fusions (IGH-FGFR3, IGH-MAF, IGH-MAFB). https://www.selleckchem.com/products/afuresertib-gsk2110183.html Of all deletions identified with follow-up, 44 (21%) resulted in a gene fusion as detected by FISH, 15 (7%) of which were fusion partners associated with high-risk multiple myeloma. All fusion-positive 3'-IGH deletions (6 fusions) resulted in high-risk IGH-FGFR3 fusions. Of the 15 high-risk fusion-positive cases, eight were without other high-risk cytogenetic findings. This study is the first to evaluate the presence of IGH gene fusions upon identification of IGH deletions and to characterize the deletion locus. Importantly, these findings indicate that follow-up FISH studies with dual fusion probes should be standard of care when IGH deletions are identified in multiple myeloma. This article is protected by copyright. All rights reserved.Background Our main objective was to review the literature to answer the following questions regarding pediatric massive transfusion (PMT) protocols 1) How is PMT defined? 2) Which blood product ratios have been investigated and what is their effect on outcomes? 3) What evidence exists regarding PMT outcomes? Methods The PRISMA guidelines were used. We searched PubMed, Google Scholar, Cochrane Library, EMBASE, Wiley Online Library, and Ovid. Articles were screened for inclusion based on relevance to PMT. Articles were assessed for study design, presence of established/tested PMT, PMT definition, PMT activation criteria, and Transfusion Ratios, for final determination of article inclusion. Results Our search produced 3213 articles with 33 included for final review. Existing definitions of PMT are based on volume administered/kg but vary in timeframe criteria (over 4 hr vs 24 hr). Some studies have investigated "high" balanced transfusion ratios as seen in adults (11 FFPpRBC) with a few showing statistically significant improvement in pediatric mortality vs lower ratios.
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  • Results Baseline characteristics and functional outcome at 90 days did not differ between the bridging and direct MTE groups. Shorter MTE procedure and hospitalization time (p = 0.025 and p = 0.036, respectively) were observed in the direct MTE group. An IVT treatment subgroup analysis showed higher rates of symptomatic ICH (p less then 0.001) and longer intervals between imaging to MTE (p = 0.005) in the full r-tPA dose group. Conclusions In patients with an MCA stroke, direct MTE seems to be a safe and equally effective as bridging therapy. The optimal r-tPA dose remains unclear. Randomized trials are needed to accurately evaluate the added value of r-tPA in patients treated with MTE.The bile acid receptor, TGR5, is a key regulator of glucose homeostasis, but the mechanisms by which TGR5 signaling improves glucose regulation are incompletely defined. https://www.selleckchem.com/products/talabostat.html In particular, TGR5 has an increasingly appreciated role in liver physiology and pathobiology; however, whether TGR5 signaling within the liver contributes to its glucoregulatory effects is unknown. Therefore, we investigated the role of hepatocyte TGR5 signaling on glucose regulation using a hepatocyte-specific TGR5 knockout mouse model. Hepatocyte-specific Tgr5Hep+/+ and Tgr5Hep-/- **** were fed a high fat diet (HFD) for 7 weeks and then orally gavaged with three doses of a highly potent, TGR5-specific agonist, Compound 18 (10 mg/kg), or vehicle, over 72 h and underwent an oral glucose tolerance test (OGTT) after the last dose. Herein, we report that TGR5 mRNA and protein is present in mouse hepatocytes. Cumulative food intake, body weight, and adiposity do not differ between Tgr5Hep+/+ and Tgr5Hep-/- **** with or without treatment with Compound 18. However, administration of Compound 18 improves glucose tolerance in Tgr5HEP+/+ ****, but not in Tgr5Hep-/- ****. Further, this effect occurred independent of body weight and GLP-1 secretion. Together, these data demonstrate that TGR5 is expressed in hepatocytes, where it functions as a key regulator of whole-body glucose homeostasis.The purpose of this research was synthesis and electron beam modification of novel ester elastomers consisting of sugar alcohol-succinic acid block and butylene glycol-succinic acid block. Four different alditols were used in the synthesis-sorbitol, erythritol, xylitol, and glycerol. The materials were irradiated with doses of 50, 100, and 150 kGy in order to determine which dose is the most beneficial. As expected, irradiation of the materials has led to the cross-link density becoming higher and improvement of the mechanical properties. Additionally, the materials were also sterilized in the process. The great advantage of elastomers described in the paper is the fact that they do not need chemical cross-linking agents or sensitizers in order to undergo radiation modification. The following tests were performed on cross-linked poly(polyol succinate-co-butylene succinate) elastomers quasi-static tensile test, determination of cross-link density, differential scanning calorimetry (DSC), dynamic thermomechanical analysis (DMTA), wettability (water contact angle), and Fourier transform infrared spectroscopy (FTIR). In order to confirm successful synthesis, prepolymers were analyzed by nuclear magnetic resonance spectroscopy (1H NMR and 13C NMR).Despite surgical resection and adjuvant therapies, stage III melanomas still have a substantial risk of relapse. Neoadjuvant therapy is an emerging strategy that might offer superior efficacy compared to adjuvant therapy. Moreover, neoadjuvant therapy has some virtual advantages it might allow for less demolitive surgery, permit the in vivo evaluation of drug efficacy, help tailor adjuvant treatments, and play a crucial role in innovative translational research. Herein, we review the available literature to explore the scientific background behind the neoadjuvant approach. We also discuss published clinical trials with a focus on predictive biomarkers and ongoing studies. Finally, we outline a possible framework for future neoadjuvant clinical trial development based on the International Neoadjuvant Melanoma Consortium guidelines.This article discusses the main uses of 1D and 2D nanomaterials in the development of conductometric gas sensors based on metal oxides. It is shown that, along with the advantages of these materials, which can improve the parameters of gas sensors, there are a number of disadvantages that significantly limit their use in the development of devices designed for the sensor market.Secretagogin (SCGN) is a calcium binding protein related to insulin release in the pancreas. Although SCGN is not co-released with insulin, plasma concentrations have been found to be increased in type 2 diabetes mellitus patients. Until now, no study on SCGN levels in pregnancy or patients with gestational diabetes mellitus (GDM) has been published. In 93 women of a high-risk population for GDM at the Medical University of Vienna, secretagogin levels of 45 GDM patients were compared to 48 women with a normal glucose tolerance (NGT). Glucose tolerance, insulin resistance and secretion were assessed with oral glucose tolerance tests (OGTT) between the 10th and 28th week of gestation (GW) and postpartum. In all women, however, predominantly in women with NGT, there was a significant positive correlation between SCGN levels and Stumvoll first (rp = 0.220, p = 0.032) and second phase index (rp = 0.224, p = 0.028). SCGN levels were not significantly different in women with NGT and GDM. However, SCGN was higher postpartum than during pregnancy (postpartum 88.07 ± 35.63 pg/mL; pregnancy 75.24 ± 37.90 pg/mL, p = 0.004). SCGN was directly correlated with week of gestation (rp = 0.308; p = 0.021) and triglycerides (rp = 0.276; p = 0.038) in women with GDM. Therefore, SCGN is related to insulin secretion and hyperinsulinemia during pregnancy; however, it does not display differences between women with NGT and GDM.Epstein-Barr virus (EBV) is closely linked to the development of a number of human cancers. EBV-associated malignancies are characterized by a restricted pattern of viral latent protein expression which is sufficient for the virus to both initiate and sustain cell growth and to protect virus-infected cells from immune attack. Expression of these EBV proteins in malignant cells provides an attractive target for therapeutic intervention. Among the viral proteins expressed in the EBV-associated epithelial malignancies, the protein encoded by the BamHI-A rightward frame 1 (BARF1) is of particular interest. BARF1 is a viral oncoprotein selectively expressed in latently infected epithelial cancers, nasopharyngeal carcinoma (NPC) and EBV-positive gastric cancer (EBV-GC). Here, we review the roles of BARF1 in oncogenesis and immunomodulation. We also discuss potential strategies for targeting the BARF1 protein as a novel therapy for EBV-driven epithelial cancers.
    Results Baseline characteristics and functional outcome at 90 days did not differ between the bridging and direct MTE groups. Shorter MTE procedure and hospitalization time (p = 0.025 and p = 0.036, respectively) were observed in the direct MTE group. An IVT treatment subgroup analysis showed higher rates of symptomatic ICH (p less then 0.001) and longer intervals between imaging to MTE (p = 0.005) in the full r-tPA dose group. Conclusions In patients with an MCA stroke, direct MTE seems to be a safe and equally effective as bridging therapy. The optimal r-tPA dose remains unclear. Randomized trials are needed to accurately evaluate the added value of r-tPA in patients treated with MTE.The bile acid receptor, TGR5, is a key regulator of glucose homeostasis, but the mechanisms by which TGR5 signaling improves glucose regulation are incompletely defined. https://www.selleckchem.com/products/talabostat.html In particular, TGR5 has an increasingly appreciated role in liver physiology and pathobiology; however, whether TGR5 signaling within the liver contributes to its glucoregulatory effects is unknown. Therefore, we investigated the role of hepatocyte TGR5 signaling on glucose regulation using a hepatocyte-specific TGR5 knockout mouse model. Hepatocyte-specific Tgr5Hep+/+ and Tgr5Hep-/- mice were fed a high fat diet (HFD) for 7 weeks and then orally gavaged with three doses of a highly potent, TGR5-specific agonist, Compound 18 (10 mg/kg), or vehicle, over 72 h and underwent an oral glucose tolerance test (OGTT) after the last dose. Herein, we report that TGR5 mRNA and protein is present in mouse hepatocytes. Cumulative food intake, body weight, and adiposity do not differ between Tgr5Hep+/+ and Tgr5Hep-/- mice with or without treatment with Compound 18. However, administration of Compound 18 improves glucose tolerance in Tgr5HEP+/+ mice, but not in Tgr5Hep-/- mice. Further, this effect occurred independent of body weight and GLP-1 secretion. Together, these data demonstrate that TGR5 is expressed in hepatocytes, where it functions as a key regulator of whole-body glucose homeostasis.The purpose of this research was synthesis and electron beam modification of novel ester elastomers consisting of sugar alcohol-succinic acid block and butylene glycol-succinic acid block. Four different alditols were used in the synthesis-sorbitol, erythritol, xylitol, and glycerol. The materials were irradiated with doses of 50, 100, and 150 kGy in order to determine which dose is the most beneficial. As expected, irradiation of the materials has led to the cross-link density becoming higher and improvement of the mechanical properties. Additionally, the materials were also sterilized in the process. The great advantage of elastomers described in the paper is the fact that they do not need chemical cross-linking agents or sensitizers in order to undergo radiation modification. The following tests were performed on cross-linked poly(polyol succinate-co-butylene succinate) elastomers quasi-static tensile test, determination of cross-link density, differential scanning calorimetry (DSC), dynamic thermomechanical analysis (DMTA), wettability (water contact angle), and Fourier transform infrared spectroscopy (FTIR). In order to confirm successful synthesis, prepolymers were analyzed by nuclear magnetic resonance spectroscopy (1H NMR and 13C NMR).Despite surgical resection and adjuvant therapies, stage III melanomas still have a substantial risk of relapse. Neoadjuvant therapy is an emerging strategy that might offer superior efficacy compared to adjuvant therapy. Moreover, neoadjuvant therapy has some virtual advantages it might allow for less demolitive surgery, permit the in vivo evaluation of drug efficacy, help tailor adjuvant treatments, and play a crucial role in innovative translational research. Herein, we review the available literature to explore the scientific background behind the neoadjuvant approach. We also discuss published clinical trials with a focus on predictive biomarkers and ongoing studies. Finally, we outline a possible framework for future neoadjuvant clinical trial development based on the International Neoadjuvant Melanoma Consortium guidelines.This article discusses the main uses of 1D and 2D nanomaterials in the development of conductometric gas sensors based on metal oxides. It is shown that, along with the advantages of these materials, which can improve the parameters of gas sensors, there are a number of disadvantages that significantly limit their use in the development of devices designed for the sensor market.Secretagogin (SCGN) is a calcium binding protein related to insulin release in the pancreas. Although SCGN is not co-released with insulin, plasma concentrations have been found to be increased in type 2 diabetes mellitus patients. Until now, no study on SCGN levels in pregnancy or patients with gestational diabetes mellitus (GDM) has been published. In 93 women of a high-risk population for GDM at the Medical University of Vienna, secretagogin levels of 45 GDM patients were compared to 48 women with a normal glucose tolerance (NGT). Glucose tolerance, insulin resistance and secretion were assessed with oral glucose tolerance tests (OGTT) between the 10th and 28th week of gestation (GW) and postpartum. In all women, however, predominantly in women with NGT, there was a significant positive correlation between SCGN levels and Stumvoll first (rp = 0.220, p = 0.032) and second phase index (rp = 0.224, p = 0.028). SCGN levels were not significantly different in women with NGT and GDM. However, SCGN was higher postpartum than during pregnancy (postpartum 88.07 ± 35.63 pg/mL; pregnancy 75.24 ± 37.90 pg/mL, p = 0.004). SCGN was directly correlated with week of gestation (rp = 0.308; p = 0.021) and triglycerides (rp = 0.276; p = 0.038) in women with GDM. Therefore, SCGN is related to insulin secretion and hyperinsulinemia during pregnancy; however, it does not display differences between women with NGT and GDM.Epstein-Barr virus (EBV) is closely linked to the development of a number of human cancers. EBV-associated malignancies are characterized by a restricted pattern of viral latent protein expression which is sufficient for the virus to both initiate and sustain cell growth and to protect virus-infected cells from immune attack. Expression of these EBV proteins in malignant cells provides an attractive target for therapeutic intervention. Among the viral proteins expressed in the EBV-associated epithelial malignancies, the protein encoded by the BamHI-A rightward frame 1 (BARF1) is of particular interest. BARF1 is a viral oncoprotein selectively expressed in latently infected epithelial cancers, nasopharyngeal carcinoma (NPC) and EBV-positive gastric cancer (EBV-GC). Here, we review the roles of BARF1 in oncogenesis and immunomodulation. We also discuss potential strategies for targeting the BARF1 protein as a novel therapy for EBV-driven epithelial cancers.
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  • The aim of this study was to investigate the influence of variant coat proteins (CPs) from different quasispecies of betanodavirus on diverse aspects of nodavirus-induced pathogenesis. It is known that variant CPs can acquire either nuclear or cytoplasmic localization, depending on the nodavirus CP genotype, and this variation may arise during viral replication and influence the regulation of host and viral gene transcription. To investigate the role of these variant CPs in pathogenesis, six variant CP expression plasmids were constructed, each containing different quasispecies CP variants from nodavirus genotype red spotted grouper nervous necrosis virus (RGNNV). The CP expression plasmids were transiently transfected into grouper GF-1 cells. At different times, the cell cycle and cell proliferation were assayed using flow cytometry and methyl thiazolyl tetrazolium (MTT) assays, respectively. The proportion of G2/M-phase GF-1 cells transfected with CP expression plasmids was higher than that of cells transfected with the blank plasmid, especially in regards to quasispecies 2 (QS2). The proliferation ratio of cells transfected with the CP expression plasmids was significantly higher than that of cells transfected with the blank plasmid, with the exception of QS6. We also found that the different quasispecies CPs downregulated the promoter activity of the tumor necrosis factor (TNF) gene to different degrees. In addition, this is the first report showing the betanodavirus CP derived from different quasispecies of RGNNV provide evidence of a chronically nodavirus-infected grouper. Overall, this study represents the first comprehensive analysis of variant CPs from grouper with persistent nodavirus infections and their effects on different aspects of pathogenesis.Apoptosis plays a key role in the immune defense against pathogen infection, and caspase is one of the most important protease enzyme families, which could initiate and execute apoptosis. Among crustaceans, several caspase genes have been reported. However, caspase in mud crab Scylla paramamosain, have not been identified yet. Here, in the present study, we characterized a new caspase, named as Sp-caspase, from S. paramamosain. The full-length cDNA sequence of Sp-caspase contained 966 bp open reading frame, encoding 322 amino acids, and its molecular weight was 36 kDa. This gene had three conserved domains of the caspase family, a prodomain, a large subunit P20 and a small subunit P10. Phylogenetic analysis showed that Sp-caspase was clustered into an effector caspase group. Sp-caspase mainly distributed in midgut, hepatopancreas, hemocytes and female ovaries, and the transcript was significantly regulated in different tissues after being challenged with Vibrio parahaemolyticus, Vibrio alginolyticus or LPS. After infection with V. alginolyticus, the apoptosis rate of hemocytes notably increased, while the mRNA level of Sp-caspase and hydrolysis activity of caspase 3/7 significantly decreased. Furthermore, in vitro assays showed that the recombinant protein tSp-caspase (deletion of Sp-caspase prodomain) could efficiently recognize and cleave human caspase 3/7 substrate Ac-DEVD-pNA, functioning as an effector caspase. Meanwhile, heterologous expression of Sp-caspase in several cell lines (HEK293T cells, HeLa cells and HighFive cells) could specifically induce cell apoptosis. Taken together, these data demonstrated that Sp-caspase could perform apoptosis as an effector caspase. In addition, it might be a negative regulator of hemocytes apoptosis under pathogen infection, which would contribute to homeostasis and immune defense of hemocytes in S. paramamosain.Polysaccharides have many functions in aquatic animals and are widely used as immunopotentiators. However, despite the emergence of serious diseases, few studies have explored the effects of Codonopsis pilosula polysaccharide (CPP) on crustaceans. We studied the effects of CPP on the growth performance, nonspecific immunity, antioxidant activity and disease resistance of red swamp crayfish (Procambarus clarkii). Healthy crayfish (5.80 ± 0.1 g) were fed diets supplemented with 0% (control), 0.05%, 0.1%, 0.15%, 0.20%, and 0.30% CPP for 8 weeks. At the end of the 8-week feeding trial, the optimal final body weight (FBW), weight gain (WG), specific growth rate (SGR), and feed conversion ratio (FCR) were observed in the crayfish fed the diets with 0.15% and 0.20% CPP, followed by those fed the diet with 0.30% CPP and then those fed the diet with 0.10% CPP, whereas the values of these parameters were obtained with the control crayfish (P less then 0.05). The crayfish fed the diets with 0.15% and 0.20% CPP exhibitcrayfish fed the diets supplemented with 0.15% and 0.20% CPP diet compared with the levels observed in the control crayfish. These results showed that dietary CPP supplementation greatly improved the growth, immunity and antioxidant capacities of crayfish, and according to the observed results, 0.15%-0.2% is the recommended optimal level of CPP dietary supplementation for crayfish.Background Autoimmune diseases comprise a spectrum of illnesses and are on the rise worldwide. Although anti-nuclear antibodies (ANA) are detected in many autoimmune diseases, up to 20% of healthy women are ANA+ and most will never develop clinical symptoms. Further, disease transition is higher among ANA+ African Americans compared to European Americans. Objective To determine the immune features that might define and prevent transition to clinical autoimmunity in ANA+ healthy individuals. https://www.selleckchem.com/ Methods We comprehensively phenotype immune profiles of African Americans and European Americans who are ANA- healthy, ANA+ healthy, or have systemic lupus erythematosus (SLE) using single cell mass cytometry, next-generation RNA sequencing, multiplex cytokine profiling, and phospho-signaling analyses. Results We found that SLE patients of both races displayed T cell expansion and elevated expression of Type I and II interferon pathways compared to both ANA- and ANA+ healthy individuals. We discovered a unique immune signature that suggests a suppressive immune phenotype and reduced CD11C+ autoimmunity-associated B cells in healthy ANA+ European Americans that is absent in their SLE or even healthy ANA- counterparts, or among African American cohorts. In contrast, ANA+ healthy African Americans exhibited elevated expression of T cell activation markers and higher plasma levels of IL-6 compared to healthy ANA+ European Americans. Conclusions We propose that this novel immune signature identified in ANA+ healthy European Americans protects them from T cell expansion, heightened activation of interferon pathways, and disease transition.
    The aim of this study was to investigate the influence of variant coat proteins (CPs) from different quasispecies of betanodavirus on diverse aspects of nodavirus-induced pathogenesis. It is known that variant CPs can acquire either nuclear or cytoplasmic localization, depending on the nodavirus CP genotype, and this variation may arise during viral replication and influence the regulation of host and viral gene transcription. To investigate the role of these variant CPs in pathogenesis, six variant CP expression plasmids were constructed, each containing different quasispecies CP variants from nodavirus genotype red spotted grouper nervous necrosis virus (RGNNV). The CP expression plasmids were transiently transfected into grouper GF-1 cells. At different times, the cell cycle and cell proliferation were assayed using flow cytometry and methyl thiazolyl tetrazolium (MTT) assays, respectively. The proportion of G2/M-phase GF-1 cells transfected with CP expression plasmids was higher than that of cells transfected with the blank plasmid, especially in regards to quasispecies 2 (QS2). The proliferation ratio of cells transfected with the CP expression plasmids was significantly higher than that of cells transfected with the blank plasmid, with the exception of QS6. We also found that the different quasispecies CPs downregulated the promoter activity of the tumor necrosis factor (TNF) gene to different degrees. In addition, this is the first report showing the betanodavirus CP derived from different quasispecies of RGNNV provide evidence of a chronically nodavirus-infected grouper. Overall, this study represents the first comprehensive analysis of variant CPs from grouper with persistent nodavirus infections and their effects on different aspects of pathogenesis.Apoptosis plays a key role in the immune defense against pathogen infection, and caspase is one of the most important protease enzyme families, which could initiate and execute apoptosis. Among crustaceans, several caspase genes have been reported. However, caspase in mud crab Scylla paramamosain, have not been identified yet. Here, in the present study, we characterized a new caspase, named as Sp-caspase, from S. paramamosain. The full-length cDNA sequence of Sp-caspase contained 966 bp open reading frame, encoding 322 amino acids, and its molecular weight was 36 kDa. This gene had three conserved domains of the caspase family, a prodomain, a large subunit P20 and a small subunit P10. Phylogenetic analysis showed that Sp-caspase was clustered into an effector caspase group. Sp-caspase mainly distributed in midgut, hepatopancreas, hemocytes and female ovaries, and the transcript was significantly regulated in different tissues after being challenged with Vibrio parahaemolyticus, Vibrio alginolyticus or LPS. After infection with V. alginolyticus, the apoptosis rate of hemocytes notably increased, while the mRNA level of Sp-caspase and hydrolysis activity of caspase 3/7 significantly decreased. Furthermore, in vitro assays showed that the recombinant protein tSp-caspase (deletion of Sp-caspase prodomain) could efficiently recognize and cleave human caspase 3/7 substrate Ac-DEVD-pNA, functioning as an effector caspase. Meanwhile, heterologous expression of Sp-caspase in several cell lines (HEK293T cells, HeLa cells and HighFive cells) could specifically induce cell apoptosis. Taken together, these data demonstrated that Sp-caspase could perform apoptosis as an effector caspase. In addition, it might be a negative regulator of hemocytes apoptosis under pathogen infection, which would contribute to homeostasis and immune defense of hemocytes in S. paramamosain.Polysaccharides have many functions in aquatic animals and are widely used as immunopotentiators. However, despite the emergence of serious diseases, few studies have explored the effects of Codonopsis pilosula polysaccharide (CPP) on crustaceans. We studied the effects of CPP on the growth performance, nonspecific immunity, antioxidant activity and disease resistance of red swamp crayfish (Procambarus clarkii). Healthy crayfish (5.80 ± 0.1 g) were fed diets supplemented with 0% (control), 0.05%, 0.1%, 0.15%, 0.20%, and 0.30% CPP for 8 weeks. At the end of the 8-week feeding trial, the optimal final body weight (FBW), weight gain (WG), specific growth rate (SGR), and feed conversion ratio (FCR) were observed in the crayfish fed the diets with 0.15% and 0.20% CPP, followed by those fed the diet with 0.30% CPP and then those fed the diet with 0.10% CPP, whereas the values of these parameters were obtained with the control crayfish (P less then 0.05). The crayfish fed the diets with 0.15% and 0.20% CPP exhibitcrayfish fed the diets supplemented with 0.15% and 0.20% CPP diet compared with the levels observed in the control crayfish. These results showed that dietary CPP supplementation greatly improved the growth, immunity and antioxidant capacities of crayfish, and according to the observed results, 0.15%-0.2% is the recommended optimal level of CPP dietary supplementation for crayfish.Background Autoimmune diseases comprise a spectrum of illnesses and are on the rise worldwide. Although anti-nuclear antibodies (ANA) are detected in many autoimmune diseases, up to 20% of healthy women are ANA+ and most will never develop clinical symptoms. Further, disease transition is higher among ANA+ African Americans compared to European Americans. Objective To determine the immune features that might define and prevent transition to clinical autoimmunity in ANA+ healthy individuals. https://www.selleckchem.com/ Methods We comprehensively phenotype immune profiles of African Americans and European Americans who are ANA- healthy, ANA+ healthy, or have systemic lupus erythematosus (SLE) using single cell mass cytometry, next-generation RNA sequencing, multiplex cytokine profiling, and phospho-signaling analyses. Results We found that SLE patients of both races displayed T cell expansion and elevated expression of Type I and II interferon pathways compared to both ANA- and ANA+ healthy individuals. We discovered a unique immune signature that suggests a suppressive immune phenotype and reduced CD11C+ autoimmunity-associated B cells in healthy ANA+ European Americans that is absent in their SLE or even healthy ANA- counterparts, or among African American cohorts. In contrast, ANA+ healthy African Americans exhibited elevated expression of T cell activation markers and higher plasma levels of IL-6 compared to healthy ANA+ European Americans. Conclusions We propose that this novel immune signature identified in ANA+ healthy European Americans protects them from T cell expansion, heightened activation of interferon pathways, and disease transition.
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  • Background Innate limitations of morphological diagnosis of T/NK-cell neoplasms mean that they can be misdiagnosed or missed, especially when mixed with a variety of benign and reactive conditions. The aim of this study was to investigate the application value of multiparameter flow cytometry immunophenotyping (****) in screening and diagnosing T/NK-cell neoplasms with cytology specimens. Material and methods The clinical and pathological characteristics of 1028 newly diagnosed cases from Fudan University Shanghai Cancer Center who provided a cytology specimen between June 2010 and January 2016 with correlated histology diagnosis and clinical confirmation were retrospectively reviewed. **** was used for screening, diagnosis and typing. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) in diagnosis of T/NK-cell neoplasms were calculated. Results There were 606 males and 422 females in 1028cases, with a mean age of 47.5 years (range 9-86 years). Specimens used foensitivity and specificity in the screening and diagnosis of T/NK-cell neoplasms and may be useful as an alternative diagnosis method in cytology specimens.Introduction The need to continually optimise CT protocols is essential to ensure the lowest possible radiation dose for the clinical task and individual patient. The aim of this study was to explore the effect of reducing effective mAs on nodule detection and radiation dose across six scanners. https://www.selleckchem.com/products/s-gsk1349572.html Methods An anthropomorphic chest phantom was scanned using a low-dose chest CT protocol, with the effective mAs lowered to the lowest permissible level. All other acquisition parameters remained consistent. Images were evaluated by five radiologists to determine their sensitivity in detecting six simulated nodules within the phantom. Image noise was calculated together with DLP. Results The lowest possible mAs achievable ranged from 7 to 19 mAs. The two highest mAs setting (17 mAs + 19 mAs) had kV modulation enabled (100 kV instead of 120 kV) which consequently resulted in a higher nodule detection rate. Overall nodule detection averaged at 91% (range 80-97%). Out of a possible 180 nodules, 16 were missed, with 12 of those 16 being the same nodule. Noise was double for the Somatom Sensation scanner when compared to the others; however, this scanner did not have iterative reconstruction and it was installed over 10 years ago. There was a strong correlation between image noise and scanner age. Conclusion This study highlighted that nodules can be detected at very low effective mAs ( less then 20 mAs) but only when other acquisition parameters are optimised i.e. iterative reconstruction and kV modulation. Nodule detection rates were affected by nodule location and image noise. Implications for practice This study consolidates previous findings on how to successfully optimise low-dose chest CT. It also highlights the difficulty with standardisation owing to factors such as scanner age and different vendor attributes.Objectives Intensive care unit patients undergo several nursing care procedures (NCP) every day. These procedures involve a risk for adverse events (AE). Yet, their prevalence, intensity, and predisposing risk factors remain poorly established. The main objective of the study was to measure the incidence and severity of NCP related AE. Design This prospective observational multicentre study was conducted in 9 ICUs. All NCP were recorded for four consecutive weeks. For each NCP, the following were collected patients' baseline characteristics, type of NCP, characteristics of the NCP, AE and therapeutic responses. Results 5849 NCP occurred in 340 patients. Among the 340 patients included, 292 (85.9%) were affected by at least one AE, and 141 (41.5%) by an SAE during a NCP. Thirty % of NCP were associated with at least one AE hemodynamic AE in 17.1%, respiratory AE in 13.6%, agitation and pain (3.7% and 3.3%). Eight invasive devices were accidentally removed. Severe Adverse Events (SAE) occurred in 5.5% of NCP. The main risk factor associated with SAE was pain/agitation at the beginning of the NCP. Conclusion AE are frequent during NCP in ICU. We identified several risk factors, some of them preventable, that could be considered for the development of recommendations for the nursing care of critically ill patients. Trial registration ClinicalTrials.gov NCT02881645.A methodology for evolving fuzzy Kalman filter identification, is proposed in this paper. The mathematical formulation contemplates the following aspects for initial estimation, an offline GK clustering algorithm and an offline fuzzy version of OKID algorithm are used to estimate antecedent and consequent parameters, respectively. From each new sample of input-output experimental data from dynamical system, the evolving eTS algorithm and an evolving fuzzy version of OKID algorithm are used to estimate the antecedent and consequent parameters of the evolving fuzzy Kalman filter, respectively. Computational and experimental results considering the estimation of states and outputs of a nonlinear dynamic system and a 2DoF helicopter, respectively, show the efficiency and applicability of the proposed methodology.This paper investigates the problem of stabilizing an n-dimensional nonlinear system whose feedback packets are transmitted via the digital network. In the presence of the bounded processing delay and network delay, the sampling time instant of a feedback packet is not the same as its receiving time instant. The larger difference between these time instants, the higher bit rate is required to stabilize the concerned system. Moreover, not only these delays, but also feedback dropouts and process noise will deteriorate the system performance. Thus we propose a model-based event-triggered control method to stabilize the system and save the occupied network bandwidth. Besides the transmission bits inside the feedback packets, their sampling time instants also convey the state information. The proposed event-triggered method can make full use of the feedback packets, especially their receiving time instant information. Compared with the periodic sampling method, our method performs better and requires lower stabilizing bit rates while the desired input-to-state stability can still be ensured.
    Background Innate limitations of morphological diagnosis of T/NK-cell neoplasms mean that they can be misdiagnosed or missed, especially when mixed with a variety of benign and reactive conditions. The aim of this study was to investigate the application value of multiparameter flow cytometry immunophenotyping (MFCI) in screening and diagnosing T/NK-cell neoplasms with cytology specimens. Material and methods The clinical and pathological characteristics of 1028 newly diagnosed cases from Fudan University Shanghai Cancer Center who provided a cytology specimen between June 2010 and January 2016 with correlated histology diagnosis and clinical confirmation were retrospectively reviewed. MFCI was used for screening, diagnosis and typing. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) in diagnosis of T/NK-cell neoplasms were calculated. Results There were 606 males and 422 females in 1028cases, with a mean age of 47.5 years (range 9-86 years). Specimens used foensitivity and specificity in the screening and diagnosis of T/NK-cell neoplasms and may be useful as an alternative diagnosis method in cytology specimens.Introduction The need to continually optimise CT protocols is essential to ensure the lowest possible radiation dose for the clinical task and individual patient. The aim of this study was to explore the effect of reducing effective mAs on nodule detection and radiation dose across six scanners. https://www.selleckchem.com/products/s-gsk1349572.html Methods An anthropomorphic chest phantom was scanned using a low-dose chest CT protocol, with the effective mAs lowered to the lowest permissible level. All other acquisition parameters remained consistent. Images were evaluated by five radiologists to determine their sensitivity in detecting six simulated nodules within the phantom. Image noise was calculated together with DLP. Results The lowest possible mAs achievable ranged from 7 to 19 mAs. The two highest mAs setting (17 mAs + 19 mAs) had kV modulation enabled (100 kV instead of 120 kV) which consequently resulted in a higher nodule detection rate. Overall nodule detection averaged at 91% (range 80-97%). Out of a possible 180 nodules, 16 were missed, with 12 of those 16 being the same nodule. Noise was double for the Somatom Sensation scanner when compared to the others; however, this scanner did not have iterative reconstruction and it was installed over 10 years ago. There was a strong correlation between image noise and scanner age. Conclusion This study highlighted that nodules can be detected at very low effective mAs ( less then 20 mAs) but only when other acquisition parameters are optimised i.e. iterative reconstruction and kV modulation. Nodule detection rates were affected by nodule location and image noise. Implications for practice This study consolidates previous findings on how to successfully optimise low-dose chest CT. It also highlights the difficulty with standardisation owing to factors such as scanner age and different vendor attributes.Objectives Intensive care unit patients undergo several nursing care procedures (NCP) every day. These procedures involve a risk for adverse events (AE). Yet, their prevalence, intensity, and predisposing risk factors remain poorly established. The main objective of the study was to measure the incidence and severity of NCP related AE. Design This prospective observational multicentre study was conducted in 9 ICUs. All NCP were recorded for four consecutive weeks. For each NCP, the following were collected patients' baseline characteristics, type of NCP, characteristics of the NCP, AE and therapeutic responses. Results 5849 NCP occurred in 340 patients. Among the 340 patients included, 292 (85.9%) were affected by at least one AE, and 141 (41.5%) by an SAE during a NCP. Thirty % of NCP were associated with at least one AE hemodynamic AE in 17.1%, respiratory AE in 13.6%, agitation and pain (3.7% and 3.3%). Eight invasive devices were accidentally removed. Severe Adverse Events (SAE) occurred in 5.5% of NCP. The main risk factor associated with SAE was pain/agitation at the beginning of the NCP. Conclusion AE are frequent during NCP in ICU. We identified several risk factors, some of them preventable, that could be considered for the development of recommendations for the nursing care of critically ill patients. Trial registration ClinicalTrials.gov NCT02881645.A methodology for evolving fuzzy Kalman filter identification, is proposed in this paper. The mathematical formulation contemplates the following aspects for initial estimation, an offline GK clustering algorithm and an offline fuzzy version of OKID algorithm are used to estimate antecedent and consequent parameters, respectively. From each new sample of input-output experimental data from dynamical system, the evolving eTS algorithm and an evolving fuzzy version of OKID algorithm are used to estimate the antecedent and consequent parameters of the evolving fuzzy Kalman filter, respectively. Computational and experimental results considering the estimation of states and outputs of a nonlinear dynamic system and a 2DoF helicopter, respectively, show the efficiency and applicability of the proposed methodology.This paper investigates the problem of stabilizing an n-dimensional nonlinear system whose feedback packets are transmitted via the digital network. In the presence of the bounded processing delay and network delay, the sampling time instant of a feedback packet is not the same as its receiving time instant. The larger difference between these time instants, the higher bit rate is required to stabilize the concerned system. Moreover, not only these delays, but also feedback dropouts and process noise will deteriorate the system performance. Thus we propose a model-based event-triggered control method to stabilize the system and save the occupied network bandwidth. Besides the transmission bits inside the feedback packets, their sampling time instants also convey the state information. The proposed event-triggered method can make full use of the feedback packets, especially their receiving time instant information. Compared with the periodic sampling method, our method performs better and requires lower stabilizing bit rates while the desired input-to-state stability can still be ensured.
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  • Generating a biofunctional film that can mimic the extracellular matrix (ECM) in an efficient and robust technique that may have great potential for medical devices, tissue engineering, and regenerative medicines. Herein, a facile approach to generate ECM biomimetic films based on the humidity-triggered relaxation of polyelectrolyte complex (PEC) nanoparticles is reported. The poly(l-lysine) and hyaluronan are precomplexed and sprayed onto a substrate, which, via a trigger of vaporous water, can be transformed into an even and stable film. The spontaneous polymer chain interfusion (diffusion coefficient ≈1.01 × 10-9 cm2 s-1 ) under saturated humidity, allowing for the rapid reorganization (within 30 min) of film morphology and structure is demonstrated. A controllable and scalable way for the loading of diversified bioactive agents, as well as on-demand modulation of stiffness is further presented. Moreover, the high-throughput arrays and programmed patterns can be easily completed, suggesting huge potentials that surpass those of state-of-the-art methods. Combined with high efficiency and flexible functionalization, it is believed that this approach should be beneficial for extending the practical applications of PEC films, such as medical implants, chip detectors, and so on.Parkinson's disease (PD) is the most common neurodegenerative disorder of movement worldwide. To date, only symptomatic treatments are available. Implantation of collagen-encapsulated human umbilical cord mesenchymal stem cells (hUC-****) is being developed as a novel therapeutic approach to potentially modify PD progression. However, implanted collagen scaffolds may induce a host tissue response. To gain insight into such response, hUC-**** were encapsulated into collagen hydrogels and implanted into the striatum of hemi-Parkinsonian male Sprague-Dawley rats. One or 14 days after implantation, the area of interest was dissected using a cryostat. Total protein extracts were subjected to tryptic digestion and subsequent LC-MS/MS analyses for protein expression profiling. Univariate and multivariate analyses were performed to identify differentially expressed protein profiles with subsequent gene ontology and pathway analysis for biological interpretation of the data; 2,219 proteins were identified by MaxQuant at 1% false discovery rate. A high correlation of label-free quantification (LFQ) protein values between biological replicates (r = .95) was observed. No significant differences were observed between brains treated with encapsulated hUC-**** compared to appropriate controls. Proteomic data were highly robust and reproducible, indicating the suitability of this approach to map differential protein expression caused by the implants. The lack of differences between conditions suggests that the effects of implantation may be minimal. Alternatively, effects may only have been focal and/or could have been masked by nonrelevant high-abundant proteins. For follow-up assessment of local changes, a more accurate dissection technique, such as laser micro dissection, and analysis method are recommended.Objective Deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) is a mainstay treatment for severe and drug-refractory essential tremor (ET). Although stimulation-induced dysarthria has been extensively described, possible impairment of swallowing has not been systematically investigated yet. Methods Twelve patients with ET and bilateral VIM-DBS with self-reported dysphagia after VIM-DBS were included. Swallowing function was assessed clinically and using by flexible endoscopic evaluation of swallowing in the stim-ON and in the stim-OFF condition. Presence, severity, and improvement of dysphagia were recorded. Results During stim-ON, the presence of dysphagia could be objectified in all patients, 42% showing mild, 42% moderate, and 16 % severe dysphagia. During stim-OFF, all patients experienced a statistically significant improvement of swallowing function. Interpretation VIM-DBS may have an impact on swallowing physiology in ET-patients. Further studies to elucidate the prevalence and underlying pathophysiological mechanisms are warranted.Liquid metal batteries are regarded as potential electrochemical systems for stationary energy storage. Currently, all reported liquid metal batteries need to be operated at temperatures above 240 °C to maintain the metallic electrodes in a molten state. Here, an unprecedented room-temperature liquid metal battery employing a sodium-potassium (Na-K) alloy anode and gallium (Ga)-based alloy cathodes is demonstrated. Compared with lead (Pb)- and mercury (Hg)-based liquid metal electrodes, the nontoxic Ga alloys maintain high environmental benignity. On the basis of improved wetting and stabilized interfacial chemistry, such liquid metal batteries deliver stable cycling performance and negligible self-discharge. Different from the conventional interphase between a typical solid electrode and a liquid electrolyte, the interphase between a liquid metal and a liquid electrolyte is directly visualized via advanced 3D chemical analysis. Insights into this new type of liquid electrode/electrolyte interphase reveal its important role in regulating charge carriers and stabilizing the redox chemistry. With facile cell fabrication, simplified battery structures, high safety, and low maintenance costs, room-temperature liquid metal batteries not only show great prospects for widespread applications, but also offer a pathway toward developing innovative energy-storage devices beyond conventional solid-state batteries or high-temperature batteries.Aquaporins are the predominant water-transporting proteins in vertebrates, but only a handful of studies have investigated aquaporin function in fish, particularly in mediating water permeability during salinity challenges. Even less is known about aquaporin function in hypoxia (low oxygen), which can profoundly affect gill function. Fish deprived of oxygen typically enlarge gill surface area and shrink the water-to-blood diffusion distance, to facilitate oxygen uptake into the bloodstream. However, these alterations to gill morphology can result in unfavorable water and ion fluxes. https://www.selleckchem.com/products/zebularine.html Thus, there exists an osmorespiratory compromise, whereby fish must try to balance high branchial gas exchange with low ion and water permeability. Furthermore, the gills of seawater and freshwater teleosts have substantially different functions with respect to osmotic and ion fluxes; consequently, hypoxia can have very different effects according to the salinity of the environment. The purpose of this study was to determine what role aquaporins play in water permeability in the hypoxia-tolerant euryhaline common killifish (Fundulus heteroclitus), in two important osmoregulatory organs-the gills and intestine.
    Generating a biofunctional film that can mimic the extracellular matrix (ECM) in an efficient and robust technique that may have great potential for medical devices, tissue engineering, and regenerative medicines. Herein, a facile approach to generate ECM biomimetic films based on the humidity-triggered relaxation of polyelectrolyte complex (PEC) nanoparticles is reported. The poly(l-lysine) and hyaluronan are precomplexed and sprayed onto a substrate, which, via a trigger of vaporous water, can be transformed into an even and stable film. The spontaneous polymer chain interfusion (diffusion coefficient ≈1.01 × 10-9 cm2 s-1 ) under saturated humidity, allowing for the rapid reorganization (within 30 min) of film morphology and structure is demonstrated. A controllable and scalable way for the loading of diversified bioactive agents, as well as on-demand modulation of stiffness is further presented. Moreover, the high-throughput arrays and programmed patterns can be easily completed, suggesting huge potentials that surpass those of state-of-the-art methods. Combined with high efficiency and flexible functionalization, it is believed that this approach should be beneficial for extending the practical applications of PEC films, such as medical implants, chip detectors, and so on.Parkinson's disease (PD) is the most common neurodegenerative disorder of movement worldwide. To date, only symptomatic treatments are available. Implantation of collagen-encapsulated human umbilical cord mesenchymal stem cells (hUC-MSCs) is being developed as a novel therapeutic approach to potentially modify PD progression. However, implanted collagen scaffolds may induce a host tissue response. To gain insight into such response, hUC-MSCs were encapsulated into collagen hydrogels and implanted into the striatum of hemi-Parkinsonian male Sprague-Dawley rats. One or 14 days after implantation, the area of interest was dissected using a cryostat. Total protein extracts were subjected to tryptic digestion and subsequent LC-MS/MS analyses for protein expression profiling. Univariate and multivariate analyses were performed to identify differentially expressed protein profiles with subsequent gene ontology and pathway analysis for biological interpretation of the data; 2,219 proteins were identified by MaxQuant at 1% false discovery rate. A high correlation of label-free quantification (LFQ) protein values between biological replicates (r = .95) was observed. No significant differences were observed between brains treated with encapsulated hUC-MSCs compared to appropriate controls. Proteomic data were highly robust and reproducible, indicating the suitability of this approach to map differential protein expression caused by the implants. The lack of differences between conditions suggests that the effects of implantation may be minimal. Alternatively, effects may only have been focal and/or could have been masked by nonrelevant high-abundant proteins. For follow-up assessment of local changes, a more accurate dissection technique, such as laser micro dissection, and analysis method are recommended.Objective Deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) is a mainstay treatment for severe and drug-refractory essential tremor (ET). Although stimulation-induced dysarthria has been extensively described, possible impairment of swallowing has not been systematically investigated yet. Methods Twelve patients with ET and bilateral VIM-DBS with self-reported dysphagia after VIM-DBS were included. Swallowing function was assessed clinically and using by flexible endoscopic evaluation of swallowing in the stim-ON and in the stim-OFF condition. Presence, severity, and improvement of dysphagia were recorded. Results During stim-ON, the presence of dysphagia could be objectified in all patients, 42% showing mild, 42% moderate, and 16 % severe dysphagia. During stim-OFF, all patients experienced a statistically significant improvement of swallowing function. Interpretation VIM-DBS may have an impact on swallowing physiology in ET-patients. Further studies to elucidate the prevalence and underlying pathophysiological mechanisms are warranted.Liquid metal batteries are regarded as potential electrochemical systems for stationary energy storage. Currently, all reported liquid metal batteries need to be operated at temperatures above 240 °C to maintain the metallic electrodes in a molten state. Here, an unprecedented room-temperature liquid metal battery employing a sodium-potassium (Na-K) alloy anode and gallium (Ga)-based alloy cathodes is demonstrated. Compared with lead (Pb)- and mercury (Hg)-based liquid metal electrodes, the nontoxic Ga alloys maintain high environmental benignity. On the basis of improved wetting and stabilized interfacial chemistry, such liquid metal batteries deliver stable cycling performance and negligible self-discharge. Different from the conventional interphase between a typical solid electrode and a liquid electrolyte, the interphase between a liquid metal and a liquid electrolyte is directly visualized via advanced 3D chemical analysis. Insights into this new type of liquid electrode/electrolyte interphase reveal its important role in regulating charge carriers and stabilizing the redox chemistry. With facile cell fabrication, simplified battery structures, high safety, and low maintenance costs, room-temperature liquid metal batteries not only show great prospects for widespread applications, but also offer a pathway toward developing innovative energy-storage devices beyond conventional solid-state batteries or high-temperature batteries.Aquaporins are the predominant water-transporting proteins in vertebrates, but only a handful of studies have investigated aquaporin function in fish, particularly in mediating water permeability during salinity challenges. Even less is known about aquaporin function in hypoxia (low oxygen), which can profoundly affect gill function. Fish deprived of oxygen typically enlarge gill surface area and shrink the water-to-blood diffusion distance, to facilitate oxygen uptake into the bloodstream. However, these alterations to gill morphology can result in unfavorable water and ion fluxes. https://www.selleckchem.com/products/zebularine.html Thus, there exists an osmorespiratory compromise, whereby fish must try to balance high branchial gas exchange with low ion and water permeability. Furthermore, the gills of seawater and freshwater teleosts have substantially different functions with respect to osmotic and ion fluxes; consequently, hypoxia can have very different effects according to the salinity of the environment. The purpose of this study was to determine what role aquaporins play in water permeability in the hypoxia-tolerant euryhaline common killifish (Fundulus heteroclitus), in two important osmoregulatory organs-the gills and intestine.
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  • Oleoresin supercritical extracts from sea buckthorn were microencapsulated in whey proteins isolate and casein, in two states native (N) and cross-linked mediated by transglutaminase (TG). The encapsulation efficiency showed values higher than 92% for total carotenoids and lycopene. Phytochemicals content was 352.90 ± 1.02 mg/g dry weight (DW) for total carotenoids in TG and 302.98 ± 2.30 mg/g DW in N, with antioxidant activity of 703.13 ± 23.60 mMol Trolox/g DW and 608.74 ± 7.12 mMol Trolox/g DW, respectively. Both powders had an inhibitory effect on α-glucosidase, of about 40% for N and 35% for TG. https://www.selleckchem.com/products/gw4869.html The presence of spherosomes was highlighted, with sizes ranging between 15.23-73.41 µm and an agglutination tendency in N, and lower sizes, up to 35 µm in TG. The in vitro digestibility revealed a prolonged release in an intestinal environment, up to 65% for TG. Moisture sorption isotherms were studied at 20 °C and the shape of curves corresponds to sigmoidal type II model. The presence of cross-linked mediated aggregates in TG powders improved stability and flowability. Our results can be used as evidence that cross-linked aggregates mediated by transglutaminase applied for microencapsulation of oleoresins have the potential to become new delivery systems, for carotenoids and lycopene, being valuable in terms of their attractive color and biological and bioaccessibility properties.Calmodulin is a ubiquitous signalling protein that controls many biological processes due to its capacity to interact and/or regulate a large number of cellular proteins and pathways, mostly in a Ca2+-dependent manner. This complex interactome of calmodulin can have pleiotropic molecular consequences, which over the years has made it often difficult to clearly define the contribution of calmodulin in the signal output of specific pathways and overall biological response. Most relevant for this review, the ability of calmodulin to influence the spatiotemporal signalling of several small GTPases, in particular KRas and Rac1, can modulate fundamental biological outcomes such as proliferation and migration. First, direct interaction of calmodulin with these GTPases can alter their subcellular localization and activation state, induce post-translational modifications as well as their ability to interact with effectors. Second, through interaction with a set of calmodulin binding proteins (CaMBPs), calmodulin can control the capacity of several guanine nucleotide exchange factors (GEFs) to promote the switch of inactive KRas and Rac1 to an active conformation. Moreover, Rac1 is also an effector of KRas and both proteins are interconnected as highlighted by the requirement for Rac1 activation in KRas-driven tumourigenesis. In this review, we attempt to summarize the multiple layers how calmodulin can regulate KRas and Rac1 GTPases in a variety of cellular events, with biological consequences and potential for therapeutic opportunities in disease settings, such as cancer.The data from the authors' earlier investigations show that molecules of zinc dithiophosphate (ZDDP) added to a lubricant can absorb energy emitted by a solid surface, which is where triboreactions occur. If the lubricant contains structures able to conduct energy, the ZDDP reactions can occur even at a relatively large distance from the solid surface, which should increase the effectiveness of ZDDP as an antiwear additive. The purpose of this paper was to verify the thesis that the tribocatalytic effect depends on the ability of the solid surface to emit electrons/energy and the ability of ordered molecular structures, such as carbon nanotubes (CNTs), to conduct energy and, most likely, to enhance the energy transfer. The tribological tests were performed using a TRB3 tribotester for 100Cr6 steel ***** and uncoated or a-CH coated HS6-5-2C steel discs. Polyalphaolefin 8 (PAO8) and PAO8 mixed with ZDDP and CNTs were used as lubricants. The results of the tribological tests suggested that (a) the effect of the interactions between ZDDP and CNTs was clearly visible; (b) the structure and properties of the solid surface layer had a significant influence on the antiwear action of the ZDDP additive.Introduction Numerous studies conducted in Europe and worldwide have indicated that employees of hospitality venues are the most exposed professional group to environmental tobacco smoke (ETS) in the workplace. The purpose of this study was to assess the exposure of employees of hospitality venues to ETS in the light of changes in anti-tobacco legislation in Poland. Materials and methods The study consisted of two stages. The first stage was conducted in 2010, while the second in 2015. The study was conducted among employees of 300 randomly selected hospitality venues in the city of Łódź (Poland). In total, 2607 questionnaires were analysed. The study used two survey questionnaires created and recommended by the Institute for Global Tobacco Control to study exposure to ETS. Statistical analysis was made with Statistica 13.1 PL (StatSoft, Poland). Results In the group of all nonsmoking employees, individuals exposed to ETS at work in 2010 accounted for 72.6%; while in 2015 it was 51.8%. Factors affecting exposure to ETS in the workplace included, among others age, marital status, education, position held, presence of a smoking room on the premises, and noncompliance with the provisions of the anti-tobacco laws. Conclusions The prevalence of tobacco smoking among employees of hospitality venues decreased in 2010-2015, however, it remained high. More than half of nonsmoking employees were exposed to ETS at work.Cerebral palsy results in the progressive loss of motor functions, with a negative impact on daily activities and participation. Despite the well described benefits of aquatic therapy in children, little is known about the effects of the same in school settings. This study aimed to describe the experience of children and youth with cerebral palsy participating in an aquatic therapy program within a special education school considering their educational and therapeutic perspectives. A qualitative descriptive case study with embedded units was developed, comprising 27 participants. This study employed purposeful sampling to include children and youth with cerebral palsy from the Asociación Ayuda a la Paralisis Cerebral (APACE) special education school, together with their parents, the special education teachers, and health care professionals. Data were collected via non-participant observation, semi-structured and informal interviews, focus groups, and researcher field notes. A thematic analysis was conducted, revealing the following themes (a) the connection with the environment; (b) postural improvements and mobility; (c) the opportunity to perform tasks; (d) learning and transfer.
    Oleoresin supercritical extracts from sea buckthorn were microencapsulated in whey proteins isolate and casein, in two states native (N) and cross-linked mediated by transglutaminase (TG). The encapsulation efficiency showed values higher than 92% for total carotenoids and lycopene. Phytochemicals content was 352.90 ± 1.02 mg/g dry weight (DW) for total carotenoids in TG and 302.98 ± 2.30 mg/g DW in N, with antioxidant activity of 703.13 ± 23.60 mMol Trolox/g DW and 608.74 ± 7.12 mMol Trolox/g DW, respectively. Both powders had an inhibitory effect on α-glucosidase, of about 40% for N and 35% for TG. https://www.selleckchem.com/products/gw4869.html The presence of spherosomes was highlighted, with sizes ranging between 15.23-73.41 µm and an agglutination tendency in N, and lower sizes, up to 35 µm in TG. The in vitro digestibility revealed a prolonged release in an intestinal environment, up to 65% for TG. Moisture sorption isotherms were studied at 20 °C and the shape of curves corresponds to sigmoidal type II model. The presence of cross-linked mediated aggregates in TG powders improved stability and flowability. Our results can be used as evidence that cross-linked aggregates mediated by transglutaminase applied for microencapsulation of oleoresins have the potential to become new delivery systems, for carotenoids and lycopene, being valuable in terms of their attractive color and biological and bioaccessibility properties.Calmodulin is a ubiquitous signalling protein that controls many biological processes due to its capacity to interact and/or regulate a large number of cellular proteins and pathways, mostly in a Ca2+-dependent manner. This complex interactome of calmodulin can have pleiotropic molecular consequences, which over the years has made it often difficult to clearly define the contribution of calmodulin in the signal output of specific pathways and overall biological response. Most relevant for this review, the ability of calmodulin to influence the spatiotemporal signalling of several small GTPases, in particular KRas and Rac1, can modulate fundamental biological outcomes such as proliferation and migration. First, direct interaction of calmodulin with these GTPases can alter their subcellular localization and activation state, induce post-translational modifications as well as their ability to interact with effectors. Second, through interaction with a set of calmodulin binding proteins (CaMBPs), calmodulin can control the capacity of several guanine nucleotide exchange factors (GEFs) to promote the switch of inactive KRas and Rac1 to an active conformation. Moreover, Rac1 is also an effector of KRas and both proteins are interconnected as highlighted by the requirement for Rac1 activation in KRas-driven tumourigenesis. In this review, we attempt to summarize the multiple layers how calmodulin can regulate KRas and Rac1 GTPases in a variety of cellular events, with biological consequences and potential for therapeutic opportunities in disease settings, such as cancer.The data from the authors' earlier investigations show that molecules of zinc dithiophosphate (ZDDP) added to a lubricant can absorb energy emitted by a solid surface, which is where triboreactions occur. If the lubricant contains structures able to conduct energy, the ZDDP reactions can occur even at a relatively large distance from the solid surface, which should increase the effectiveness of ZDDP as an antiwear additive. The purpose of this paper was to verify the thesis that the tribocatalytic effect depends on the ability of the solid surface to emit electrons/energy and the ability of ordered molecular structures, such as carbon nanotubes (CNTs), to conduct energy and, most likely, to enhance the energy transfer. The tribological tests were performed using a TRB3 tribotester for 100Cr6 steel balls and uncoated or a-CH coated HS6-5-2C steel discs. Polyalphaolefin 8 (PAO8) and PAO8 mixed with ZDDP and CNTs were used as lubricants. The results of the tribological tests suggested that (a) the effect of the interactions between ZDDP and CNTs was clearly visible; (b) the structure and properties of the solid surface layer had a significant influence on the antiwear action of the ZDDP additive.Introduction Numerous studies conducted in Europe and worldwide have indicated that employees of hospitality venues are the most exposed professional group to environmental tobacco smoke (ETS) in the workplace. The purpose of this study was to assess the exposure of employees of hospitality venues to ETS in the light of changes in anti-tobacco legislation in Poland. Materials and methods The study consisted of two stages. The first stage was conducted in 2010, while the second in 2015. The study was conducted among employees of 300 randomly selected hospitality venues in the city of Łódź (Poland). In total, 2607 questionnaires were analysed. The study used two survey questionnaires created and recommended by the Institute for Global Tobacco Control to study exposure to ETS. Statistical analysis was made with Statistica 13.1 PL (StatSoft, Poland). Results In the group of all nonsmoking employees, individuals exposed to ETS at work in 2010 accounted for 72.6%; while in 2015 it was 51.8%. Factors affecting exposure to ETS in the workplace included, among others age, marital status, education, position held, presence of a smoking room on the premises, and noncompliance with the provisions of the anti-tobacco laws. Conclusions The prevalence of tobacco smoking among employees of hospitality venues decreased in 2010-2015, however, it remained high. More than half of nonsmoking employees were exposed to ETS at work.Cerebral palsy results in the progressive loss of motor functions, with a negative impact on daily activities and participation. Despite the well described benefits of aquatic therapy in children, little is known about the effects of the same in school settings. This study aimed to describe the experience of children and youth with cerebral palsy participating in an aquatic therapy program within a special education school considering their educational and therapeutic perspectives. A qualitative descriptive case study with embedded units was developed, comprising 27 participants. This study employed purposeful sampling to include children and youth with cerebral palsy from the Asociación Ayuda a la Paralisis Cerebral (APACE) special education school, together with their parents, the special education teachers, and health care professionals. Data were collected via non-participant observation, semi-structured and informal interviews, focus groups, and researcher field notes. A thematic analysis was conducted, revealing the following themes (a) the connection with the environment; (b) postural improvements and mobility; (c) the opportunity to perform tasks; (d) learning and transfer.
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  • 6%), with renal complications and road traffic accidents accounting for 2.2% each. Patients' age ranged from 31 to 84 years, with a modal age of 57 years. There was a male predominance with a male-to-female ratio of 1.51. Systemic hypertension co-morbidity was statistically significantly more common in patients aged 60 and above (P = 0.035). The most common lesion observed in the kidneys was benign nephrosclerosis (43.2%). Conclusions This study suggests that majority of our patients with diabetes mellitus die from infections with attendant sepsis. Older patients appear to have co-morbid systemic hypertension. Patient education on infection prevention and prompt treatment might be life-saving.Hypertension or high blood pressure is the foremost risk factor of cardiovascular diseases which in turn are the leading cause of death globally. Despite the widespread use of antihypertensive medication, the condition remains a global health concern. In a bid to ascertain that other therapies such as psychological treatment may be adopted as complementary treatments for hypertension, this paper therefore examines literature on the effectiveness of behavioural therapy in the treatment of hypertension, identify the technique which seems most effective though blood pressure reductions, highlight other hypertension-related domains and report sustainability of blood pressure control post-intervention. A systematic literature review of randomised control trials reporting the effectiveness of behaviour therapy on blood pressure among hypertensive adults, published between the years 2014 and 2018, was conducted. A total of 79 articles were identified from the database search after which 11 met the inclusion criteria, with 10 of the 11 studies reporting behavioural therapy to be effective in blood pressure control. https://www.selleckchem.com/products/pu-h71.html Relaxation therapy and meditation training appeared to be most effective as they brought about the most significant decrements in blood pressure. The mean blood pressure reduction ranged from 2.88-36.33 mmHg (systolic) to 0.04-21.48 mmHg (diastolic). Blood pressure control was found to have been sustained from between 0.7 and 24 months post-intervention. From this current paper, behaviour intervention is a viable, albeit complementary treatment method for hypertension; however, there is the need for more research to be conducted in various parts of the world, specifically in Nigeria and in Africa at large to allow for more relatable report on this topic.Sample size is one of the important considerations at the planning phase of a research proposal, but researchers are often faced with challenges of estimating valid sample size. Many researchers frequently use inadequate sample size and this invariably introduces errors into the final findings. Many reviews on sample size estimation have focused more on specific study designs which often present technical equations and formula that are boring to statistically naïve health researchers. Therefore, this compendium reviews all the common sample size estimation formula in social science and health research with the aim of providing basic guidelines and principles to achieve valid sample size estimation. The simplification of the sample size formula and detailed explanation in this review will demystify the difficulties many students as well as some researchers have with statistical formulae for sample size estimation.Background/Aim The treatment efficacy of Helicobacter pylori (H. pylori) has been decreasing over time due to resistance to multiple antimicrobial therapies. The most effective treatment regimen for Saudi Arabian patients infected with H. pylori is still unknown. We aimed to study the eradication rate of 10 days of quadruple therapy; bismuth subcitrate potassium 140 mg, metronidazole 125 mg, and tetracycline 125 mg for H. pylori infection in a Saudi population. Patients and Methods This was a prospective, open-label, non-randomized controlled trial. Patients with H. pylori infection were diagnosed by upper gastrointestinal (GI) endoscopy and rapid urease test (RUT) or histology. Patients who tested positive were recruited. Eligible patients were prescribed a 10-day course of quadruple therapy and received three capsules 4 times daily for 10 days along with omeprazole 20 mg twice daily. H. pylori was considered eradicated if the urea breath test (UBT) was negative after 6 weeks of completing the treatment. Results Ninety-two patients with H. pylori infection were recruited. Three patients withdrew from the trial and another seven patients lost follow-up. We analyzed 82 patient's data as per-protocol analysis, of whom 66 (80%) were naive to H. pylori treatment. Four patients had failed previous treatment with the sequential regimen and 12 patients had treatment with clarithromycin-based triple therapy. The post-treatment UBT for H. pylori infection was negative by per-protocol analysis in 72/82 patients (87.8%), and 72/92 (78.3%) by intention-to-treat analysis. There was no correlation between previous treatment failure and treatment response to the bismuth-based quadruple therapy (P value = 0.28). Conclusions Treatment with a bismuth-based quadruple therapy was effective in eradicating H. pylori infection in 78.3% of Saudi patients with an ITT analysis and in 87.8% as per-protocol analysis.Background/Aim Treatment of Helicobacter pylori infections has become more difficult because of increasing antibiotic resistance. We assessed the efficacy and safety of treatment with probiotics followed by a tetracycline- and furazolidone-containing quadruple regimen as rescue treatment for H. pylori infection. Patients and Methods This retrospective study examined patients with at least two H. pylori eradication failures. Patients were given a two-week compound Lactobacillus acidophilus (1 g t.i.d.), followed by a quadruple antibiotic regimen (esomeprazole [20 mg b.i.d.] + bismuth potassium citrate [220 mg b.i.d.] + tetracycline [750 mg b.i.d.] + furazolidone [100 mg b.i.d.]) for 10 days as rescue therapy. Eradication was evaluated using the[13]C-urea breath test at 4 weeks after the end of therapy, and side effects were recorded. Results The records of 50 patients were examined. Four cases experienced treatment failure, and one case received replacement with metronidazole because of allergy to furazolidone.
    6%), with renal complications and road traffic accidents accounting for 2.2% each. Patients' age ranged from 31 to 84 years, with a modal age of 57 years. There was a male predominance with a male-to-female ratio of 1.51. Systemic hypertension co-morbidity was statistically significantly more common in patients aged 60 and above (P = 0.035). The most common lesion observed in the kidneys was benign nephrosclerosis (43.2%). Conclusions This study suggests that majority of our patients with diabetes mellitus die from infections with attendant sepsis. Older patients appear to have co-morbid systemic hypertension. Patient education on infection prevention and prompt treatment might be life-saving.Hypertension or high blood pressure is the foremost risk factor of cardiovascular diseases which in turn are the leading cause of death globally. Despite the widespread use of antihypertensive medication, the condition remains a global health concern. In a bid to ascertain that other therapies such as psychological treatment may be adopted as complementary treatments for hypertension, this paper therefore examines literature on the effectiveness of behavioural therapy in the treatment of hypertension, identify the technique which seems most effective though blood pressure reductions, highlight other hypertension-related domains and report sustainability of blood pressure control post-intervention. A systematic literature review of randomised control trials reporting the effectiveness of behaviour therapy on blood pressure among hypertensive adults, published between the years 2014 and 2018, was conducted. A total of 79 articles were identified from the database search after which 11 met the inclusion criteria, with 10 of the 11 studies reporting behavioural therapy to be effective in blood pressure control. https://www.selleckchem.com/products/pu-h71.html Relaxation therapy and meditation training appeared to be most effective as they brought about the most significant decrements in blood pressure. The mean blood pressure reduction ranged from 2.88-36.33 mmHg (systolic) to 0.04-21.48 mmHg (diastolic). Blood pressure control was found to have been sustained from between 0.7 and 24 months post-intervention. From this current paper, behaviour intervention is a viable, albeit complementary treatment method for hypertension; however, there is the need for more research to be conducted in various parts of the world, specifically in Nigeria and in Africa at large to allow for more relatable report on this topic.Sample size is one of the important considerations at the planning phase of a research proposal, but researchers are often faced with challenges of estimating valid sample size. Many researchers frequently use inadequate sample size and this invariably introduces errors into the final findings. Many reviews on sample size estimation have focused more on specific study designs which often present technical equations and formula that are boring to statistically naïve health researchers. Therefore, this compendium reviews all the common sample size estimation formula in social science and health research with the aim of providing basic guidelines and principles to achieve valid sample size estimation. The simplification of the sample size formula and detailed explanation in this review will demystify the difficulties many students as well as some researchers have with statistical formulae for sample size estimation.Background/Aim The treatment efficacy of Helicobacter pylori (H. pylori) has been decreasing over time due to resistance to multiple antimicrobial therapies. The most effective treatment regimen for Saudi Arabian patients infected with H. pylori is still unknown. We aimed to study the eradication rate of 10 days of quadruple therapy; bismuth subcitrate potassium 140 mg, metronidazole 125 mg, and tetracycline 125 mg for H. pylori infection in a Saudi population. Patients and Methods This was a prospective, open-label, non-randomized controlled trial. Patients with H. pylori infection were diagnosed by upper gastrointestinal (GI) endoscopy and rapid urease test (RUT) or histology. Patients who tested positive were recruited. Eligible patients were prescribed a 10-day course of quadruple therapy and received three capsules 4 times daily for 10 days along with omeprazole 20 mg twice daily. H. pylori was considered eradicated if the urea breath test (UBT) was negative after 6 weeks of completing the treatment. Results Ninety-two patients with H. pylori infection were recruited. Three patients withdrew from the trial and another seven patients lost follow-up. We analyzed 82 patient's data as per-protocol analysis, of whom 66 (80%) were naive to H. pylori treatment. Four patients had failed previous treatment with the sequential regimen and 12 patients had treatment with clarithromycin-based triple therapy. The post-treatment UBT for H. pylori infection was negative by per-protocol analysis in 72/82 patients (87.8%), and 72/92 (78.3%) by intention-to-treat analysis. There was no correlation between previous treatment failure and treatment response to the bismuth-based quadruple therapy (P value = 0.28). Conclusions Treatment with a bismuth-based quadruple therapy was effective in eradicating H. pylori infection in 78.3% of Saudi patients with an ITT analysis and in 87.8% as per-protocol analysis.Background/Aim Treatment of Helicobacter pylori infections has become more difficult because of increasing antibiotic resistance. We assessed the efficacy and safety of treatment with probiotics followed by a tetracycline- and furazolidone-containing quadruple regimen as rescue treatment for H. pylori infection. Patients and Methods This retrospective study examined patients with at least two H. pylori eradication failures. Patients were given a two-week compound Lactobacillus acidophilus (1 g t.i.d.), followed by a quadruple antibiotic regimen (esomeprazole [20 mg b.i.d.] + bismuth potassium citrate [220 mg b.i.d.] + tetracycline [750 mg b.i.d.] + furazolidone [100 mg b.i.d.]) for 10 days as rescue therapy. Eradication was evaluated using the[13]C-urea breath test at 4 weeks after the end of therapy, and side effects were recorded. Results The records of 50 patients were examined. Four cases experienced treatment failure, and one case received replacement with metronidazole because of allergy to furazolidone.
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