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  • An amendment to this paper has been published and can be accessed via a link at the top of the paper.We report and demonstrate for the first time a method to compensate atmospheric group velocity dispersion of terahertz pulses. In ultra-wideband or impulse radio terahertz wireless communication, the atmosphere reshapes terahertz pulses via group velocity dispersion, a result of the frequency-dependent refractivity of air. Without correction, this can significantly degrade the achievable data transmission rate. We present a method for compensating the atmospheric dispersion of terahertz pulses using a cohort of stratified media reflectors. Using this method, we compensated group velocity dispersion in the 0.2-0.3 THz channel under common atmospheric conditions. Based on analytic and numerical simulations, the method can exhibit an in-band power efficiency of greater than 98% and dispersion compensation up to 99% of ideal. Simulations were validated by experimental measurements.Inland waters (rivers, lakes and ponds) are important conduits for the emission of terrestrial carbon in Arctic permafrost landscapes. These emissions are driven by turnover of contemporary terrestrial carbon and additional pre-aged (Holocene and late-Pleistocene) carbon released from thawing permafrost soils, but the magnitude of these source contributions to total inland water carbon fluxes remains unknown. https://www.selleckchem.com/products/wnk-in-11.html Here we present unique simultaneous radiocarbon age measurements of inland water CO2, CH4 and dissolved and particulate organic carbon in northeast Siberia during summer. We show that >80% of total inland water carbon was contemporary in age, but pre-aged carbon contributed >50% at sites strongly affected by permafrost thaw. CO2 and CH4 were younger than dissolved and particulate organic carbon, suggesting emissions were primarily fuelled by contemporary carbon decomposition. Our findings reveal that inland water carbon emissions from permafrost landscapes may be more sensitive to changes in contemporary carbon turnover than the release of pre-aged carbon from thawing permafrost.An amendment to this paper has been published and can be accessed via a link at the top of the paper.An amendment to this paper has been published and can be accessed via a link at the top of the paper.Non-targeted and suspect analyses with liquid chromatography/electrospray/high-resolution mass spectrometry (LC/ESI/HRMS) are gaining importance as they enable identification of hundreds or even thousands of compounds in a single sample. Here, we present an approach to address the challenge to quantify compounds identified from LC/HRMS data without authentic standards. The approach uses random forest regression to predict the response of the compounds in ESI/HRMS with a mean error of 2.2 and 2.0 times for ESI positive and negative mode, respectively. We observe that the predicted responses can be transferred between different instruments via a regression approach. Furthermore, we applied the predicted responses to estimate the concentration of the compounds without the standard substances. The approach was validated by quantifying pesticides and mycotoxins in six different cereal samples. For applicability, the accuracy of the concentration prediction needs to be compatible with the effect (e.g. toxicology) predictions. We achieved the average quantification error of 5.4 times, which is well compatible with the accuracy of the toxicology predictions.The non-aqueous asymmetric lithium ion hybrid capacitor (LIHC) is a tactical energy storage device composed of a faradic and non-faradic electrode pair, which aims to achieve both high energy and great power densities. On the other hand, the different types of electrode combinations cause severe imbalances in energy and power capabilities, leading to poor electrochemical performance. Herein, waste pinecone-derived hierarchically porous pyropolymers (WP-HPPs) were fabricated as a surface-driven pseudocapacitive electrode, which has the advantages of both faradic and non-faradic electrodes. The unique materials properties of WP-HPPs possessing high effective surface areas and hierarchically open nanopores led to high specific capacities of ~412 mA h g-1 and considerable rate/cycling performance as a cathode for LIHCs. In particular, nanometer-scale pores, approximately 3 nm in size, plays a key role in the pseudocapacitive charge storage behaviors because open nanopores can transport solvated Li-ions easily into the inside of complex carbon structures and a large specific surface area can be provided by the effective active surface for charge storage. In addition, WP-HPP-based asymmetric LIHCs assembled with a pseudocapacitive counterpart demonstrated feasible electrochemical performance, such as maximum specific energy and specific power of ~340 Wh kg-1 and ~11,000 W kg-1, respectively, with significant cycling stability.CRISPR-based screening methods using single-cell RNA sequencing (scRNA-seq) technology enable comprehensive profiling of gene perturbations from knock-out mutations. However, evaluating substitution mutations using scRNA-seq is currently limited. We combined CRISPR RNA-guided deaminase and scRNA-seq technology to develop a platform for introducing mutations in multiple genes and assessing the mutation-associated signatures. Using this platform, we generated a library consisting of 420 sgRNAs, performed sgRNA tracking analysis, and assessed the effect size of the response to vemurafenib in the human melanoma cell line, which has been well-studied via knockout-based drop-out screens. However, a substitution mutation library screen has not been applied and transcriptional information for mechanisms of action was not assessed. Our platform permits discrimination of several candidate mutations that function differently from other mutations by integrating sgRNA candidates and gene expression readout. We anticipate that our platform will enable high-throughput analyses of the mechanisms related to a variety of biological events.Gastroenteritis is common among children. Campylobacter jejuni is one of the main causative bacterial pathogens, together with Shigella, Salmonella and invasive Escherichia coli. Campylobacteriosis is a zoonotic, usually self-limited disease that does not always require antibiotic treatment. In cases of protracted diarrhoea in healthy children or immunocompromised patients, antibiotic treatment is recommended, and the drug of choice is still macrolides, with very low resistance rates in Campylobacter species. However, it is crucial to isolate the causative organism, because some cases, such as Shigella encephalitis, call for initiation of empiric antibiotic treatment. In this study, we compared the incidence, epidemiology, clinical findings and laboratory results of gastroenteritis with dysentery caused by these organisms in children in our area. C. jejuni was found to be the leading pathogen in children hospitalized with bacterial gastroenteritis, followed by Shigella and Salmonella. Macrolides were the drug of choice for Campylobacter, and ceftriaxone and ciprofloxacin were the best empiric treatments for Shigella and Salmonella, respectively.
    An amendment to this paper has been published and can be accessed via a link at the top of the paper.We report and demonstrate for the first time a method to compensate atmospheric group velocity dispersion of terahertz pulses. In ultra-wideband or impulse radio terahertz wireless communication, the atmosphere reshapes terahertz pulses via group velocity dispersion, a result of the frequency-dependent refractivity of air. Without correction, this can significantly degrade the achievable data transmission rate. We present a method for compensating the atmospheric dispersion of terahertz pulses using a cohort of stratified media reflectors. Using this method, we compensated group velocity dispersion in the 0.2-0.3 THz channel under common atmospheric conditions. Based on analytic and numerical simulations, the method can exhibit an in-band power efficiency of greater than 98% and dispersion compensation up to 99% of ideal. Simulations were validated by experimental measurements.Inland waters (rivers, lakes and ponds) are important conduits for the emission of terrestrial carbon in Arctic permafrost landscapes. These emissions are driven by turnover of contemporary terrestrial carbon and additional pre-aged (Holocene and late-Pleistocene) carbon released from thawing permafrost soils, but the magnitude of these source contributions to total inland water carbon fluxes remains unknown. https://www.selleckchem.com/products/wnk-in-11.html Here we present unique simultaneous radiocarbon age measurements of inland water CO2, CH4 and dissolved and particulate organic carbon in northeast Siberia during summer. We show that >80% of total inland water carbon was contemporary in age, but pre-aged carbon contributed >50% at sites strongly affected by permafrost thaw. CO2 and CH4 were younger than dissolved and particulate organic carbon, suggesting emissions were primarily fuelled by contemporary carbon decomposition. Our findings reveal that inland water carbon emissions from permafrost landscapes may be more sensitive to changes in contemporary carbon turnover than the release of pre-aged carbon from thawing permafrost.An amendment to this paper has been published and can be accessed via a link at the top of the paper.An amendment to this paper has been published and can be accessed via a link at the top of the paper.Non-targeted and suspect analyses with liquid chromatography/electrospray/high-resolution mass spectrometry (LC/ESI/HRMS) are gaining importance as they enable identification of hundreds or even thousands of compounds in a single sample. Here, we present an approach to address the challenge to quantify compounds identified from LC/HRMS data without authentic standards. The approach uses random forest regression to predict the response of the compounds in ESI/HRMS with a mean error of 2.2 and 2.0 times for ESI positive and negative mode, respectively. We observe that the predicted responses can be transferred between different instruments via a regression approach. Furthermore, we applied the predicted responses to estimate the concentration of the compounds without the standard substances. The approach was validated by quantifying pesticides and mycotoxins in six different cereal samples. For applicability, the accuracy of the concentration prediction needs to be compatible with the effect (e.g. toxicology) predictions. We achieved the average quantification error of 5.4 times, which is well compatible with the accuracy of the toxicology predictions.The non-aqueous asymmetric lithium ion hybrid capacitor (LIHC) is a tactical energy storage device composed of a faradic and non-faradic electrode pair, which aims to achieve both high energy and great power densities. On the other hand, the different types of electrode combinations cause severe imbalances in energy and power capabilities, leading to poor electrochemical performance. Herein, waste pinecone-derived hierarchically porous pyropolymers (WP-HPPs) were fabricated as a surface-driven pseudocapacitive electrode, which has the advantages of both faradic and non-faradic electrodes. The unique materials properties of WP-HPPs possessing high effective surface areas and hierarchically open nanopores led to high specific capacities of ~412 mA h g-1 and considerable rate/cycling performance as a cathode for LIHCs. In particular, nanometer-scale pores, approximately 3 nm in size, plays a key role in the pseudocapacitive charge storage behaviors because open nanopores can transport solvated Li-ions easily into the inside of complex carbon structures and a large specific surface area can be provided by the effective active surface for charge storage. In addition, WP-HPP-based asymmetric LIHCs assembled with a pseudocapacitive counterpart demonstrated feasible electrochemical performance, such as maximum specific energy and specific power of ~340 Wh kg-1 and ~11,000 W kg-1, respectively, with significant cycling stability.CRISPR-based screening methods using single-cell RNA sequencing (scRNA-seq) technology enable comprehensive profiling of gene perturbations from knock-out mutations. However, evaluating substitution mutations using scRNA-seq is currently limited. We combined CRISPR RNA-guided deaminase and scRNA-seq technology to develop a platform for introducing mutations in multiple genes and assessing the mutation-associated signatures. Using this platform, we generated a library consisting of 420 sgRNAs, performed sgRNA tracking analysis, and assessed the effect size of the response to vemurafenib in the human melanoma cell line, which has been well-studied via knockout-based drop-out screens. However, a substitution mutation library screen has not been applied and transcriptional information for mechanisms of action was not assessed. Our platform permits discrimination of several candidate mutations that function differently from other mutations by integrating sgRNA candidates and gene expression readout. We anticipate that our platform will enable high-throughput analyses of the mechanisms related to a variety of biological events.Gastroenteritis is common among children. Campylobacter jejuni is one of the main causative bacterial pathogens, together with Shigella, Salmonella and invasive Escherichia coli. Campylobacteriosis is a zoonotic, usually self-limited disease that does not always require antibiotic treatment. In cases of protracted diarrhoea in healthy children or immunocompromised patients, antibiotic treatment is recommended, and the drug of choice is still macrolides, with very low resistance rates in Campylobacter species. However, it is crucial to isolate the causative organism, because some cases, such as Shigella encephalitis, call for initiation of empiric antibiotic treatment. In this study, we compared the incidence, epidemiology, clinical findings and laboratory results of gastroenteritis with dysentery caused by these organisms in children in our area. C. jejuni was found to be the leading pathogen in children hospitalized with bacterial gastroenteritis, followed by Shigella and Salmonella. Macrolides were the drug of choice for Campylobacter, and ceftriaxone and ciprofloxacin were the best empiric treatments for Shigella and Salmonella, respectively.
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  • Objective Whole-body MRI (WBMRI) is promising for monitoring patients' global disease activity in inflammatory joint diseases. The validation of WBMRI is limited; no studies have evaluated the test-retest agreement (interscan agreement) and only few have assessed the intra- and interreader agreement. Therefore we examined the interscan agreement of WBMRI in patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA) and healthy controls (HC); and secondly evaluated the intraand interreader agreement and agreement with conventional hand MRI and determined the distribution of lesions. Methods WBMRI was performed twice with a one-week interval in 14 patients with PsA, 10 with RA and 16 HC. Images were anonymized and read in pairs with unknown chronological order by experienced readers according to the OMERACT WBMRI, the Canada-Denmark MRI and the RAMRIS/PsAMRIS scoring systems. Ten image sets were re-anonymized for assessment of intraand interreader agreement. Agreement was calculated on lesion level by percentage exact agreement (PEA) and Cohen's kappa, and for sum scores by absolute agreement single-measure intraclass correlation coefficient (ICC). Results WBMRI of the spine and peripheral joints and entheses generally showed moderate to almost perfect interscan agreement with PEA ranging from 95-100%, kappa 0.71-1.00 and ICC 0.95-1.00. https://www.selleckchem.com/products/gsk591-epz015866-gsk3203591.html Intra- and interreader data generally showed moderate to almost perfect agreement. Agreement with conventional MRI varied. More lesions were found in patients than HC. Conclusion WBMRI showed good interscan agreement, implying that repositioning of the patient between examinations does not markedly affect scoring of lesions. Intra- and interreader agreement was moderate to almost perfect.Objective To assess pulmonary function and Chronic Obstructive Pulmonary Disease (COPD) development over time in patients with primary Sjögren's Syndrome (pSS) and the association between pulmonary function, radiographic findings, respiratory symptoms and clinical features of pSS, taking cigarette consumption into account. Methods Forty patients with pSS (mean age 66 yrs, range 42-81 yrs, 39 women), previously participating in a cross-sectional study on pulmonary involvement in pSS, were re-assessed by pulmonary function tests after a mean follow-up time of six years. At follow-up, patients were also assessed by high-resolution computed tomography (HRCT) of the chest and for pSS disease activity, respiratory symptoms and cigarette consumption. Results Patients with pSS showed significantly decreased percentages of predicted total lung capacity (TLC), residual volume (RV), RV/ TLC ratio and diffusing capacity of the lungs for carbon monoxide (DL,CO), and an increased percentage of predicted forced expiratory volume in one second/vital capacity (FEV1/VC) ratio from baseline to follow-up. The proportion of COPD did not change significantly from baseline to follow-up (38% vs. 40%). Radiographic signs of bronchial involvement and interstitial lung disease were found in 38% of the patients, respectively. Conclusion Both airway and pulmonary parenchymal disease were commonly found in pSS patients, with a co-existence of both an obstructive and a restrictive pulmonary function pattern, where the latter tended to deteriorate over time. COPD was still a common finding. Airway and pulmonary involvement may be underdiagnosed in pSS, why special attention to clinical assessment of pulmonary involvement in pSS patients is mandated.Objective To determine if a one-year change in walking speed is associated with receiving an incident knee replacement during the following year in adults with and at risk for knee osteoarthritis (OA). Methods Using data from the Osteoarthritis Initiative, we determined a one-year change in 20- meter walk speed from three observation periods (i.e., 0-12, 12-24, and 24-36 month). We operationally defined one-year change in walking speed as either 1) decline 0.1 m/s change. Incident knee replacement was defined using each subsequent one-year period (i.e., 12-24, 24- 36, and 36-48 month). Combining data from the three observation periods, we performed a Poisson regression with robust error variance to determine the relative risk between a change in walking speed (exposure) and incident knee replacement over the following year (outcome). Results Of the 4,264 participants included within this analysis (11,311 total person visits), 115 (3%) adults received a knee replacement. Decline in walking speed was associated with a 104% increase in risk [adjusted relative risk (RR)=2.04; 95% confidence interval (CI)= 1.40-2.98], while an increase in walking speed associated with a 55% decrease in risk (RR=0.45; 95% CI=0.22-0.93) of incident knee replacement in the following year compared to a person with no change in walking speed. Conclusion A one-year decline in walking speed is associated with an increased risk, while one-year increase in walking speed is associated with a decreased risk of future incident knee replacement.Objective Early diagnosis of systemic sclerosis (SSc) is imperative and Raynaud's phenomenon (RP) is an important component of progressive vasculopathy. Nailfold videocapillaroscopy (NVC) is a wellestablished tool that can quantify structural vascular abnormalities. Digital thermal monitoring (DTM) assesses microvascular functional dysfunction related to thermoregulation. In this study, we investigated the correlation of NVC patterns and DTM variables in SSc patients. Methods Patients with SSc by 2013 ACR/EULAR criteria that were consented into the clinical care registry had NVC and DTM performed. For NVC, the number of capillaries (density), measurement of apical diameter (dimension), presence or absence of hemorrhages and number of abnormal shapes were assessed to categorize three different qualitative patterns 'early', 'active' and 'late'. For DTM, Doppler ultrasound hyperemic, low frequency, blood velocity of radial artery and fingertip vascular function was assessed and a vascular reactive index (VRI) measurement was automated. Statistical evaluation was performed by non-parametric tests to assess the correlation of NVC and VRI. Results Thirty-one SSc subjects with interpretable NVC and DTM performed on the same day were included in the study. VRI was progressively higher in SSc patients with the 'early', 'active' and 'late' NVC patterns of microangiopathy (p less then 0.0001). There was a significant negative correlation between VRI and microhemorrhages score (r=-0.363, p=0.044). Conclusion Our study suggests that more advanced vasculopathy correlates to reduced microvascular function as detected by DTM and more advanced structural abnormalities detected by NVC. NVC and DTM may provide different aspects of vasculopathy quantification and complement each other as investigative tools.
    Objective Whole-body MRI (WBMRI) is promising for monitoring patients' global disease activity in inflammatory joint diseases. The validation of WBMRI is limited; no studies have evaluated the test-retest agreement (interscan agreement) and only few have assessed the intra- and interreader agreement. Therefore we examined the interscan agreement of WBMRI in patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA) and healthy controls (HC); and secondly evaluated the intraand interreader agreement and agreement with conventional hand MRI and determined the distribution of lesions. Methods WBMRI was performed twice with a one-week interval in 14 patients with PsA, 10 with RA and 16 HC. Images were anonymized and read in pairs with unknown chronological order by experienced readers according to the OMERACT WBMRI, the Canada-Denmark MRI and the RAMRIS/PsAMRIS scoring systems. Ten image sets were re-anonymized for assessment of intraand interreader agreement. Agreement was calculated on lesion level by percentage exact agreement (PEA) and Cohen's kappa, and for sum scores by absolute agreement single-measure intraclass correlation coefficient (ICC). Results WBMRI of the spine and peripheral joints and entheses generally showed moderate to almost perfect interscan agreement with PEA ranging from 95-100%, kappa 0.71-1.00 and ICC 0.95-1.00. https://www.selleckchem.com/products/gsk591-epz015866-gsk3203591.html Intra- and interreader data generally showed moderate to almost perfect agreement. Agreement with conventional MRI varied. More lesions were found in patients than HC. Conclusion WBMRI showed good interscan agreement, implying that repositioning of the patient between examinations does not markedly affect scoring of lesions. Intra- and interreader agreement was moderate to almost perfect.Objective To assess pulmonary function and Chronic Obstructive Pulmonary Disease (COPD) development over time in patients with primary Sjögren's Syndrome (pSS) and the association between pulmonary function, radiographic findings, respiratory symptoms and clinical features of pSS, taking cigarette consumption into account. Methods Forty patients with pSS (mean age 66 yrs, range 42-81 yrs, 39 women), previously participating in a cross-sectional study on pulmonary involvement in pSS, were re-assessed by pulmonary function tests after a mean follow-up time of six years. At follow-up, patients were also assessed by high-resolution computed tomography (HRCT) of the chest and for pSS disease activity, respiratory symptoms and cigarette consumption. Results Patients with pSS showed significantly decreased percentages of predicted total lung capacity (TLC), residual volume (RV), RV/ TLC ratio and diffusing capacity of the lungs for carbon monoxide (DL,CO), and an increased percentage of predicted forced expiratory volume in one second/vital capacity (FEV1/VC) ratio from baseline to follow-up. The proportion of COPD did not change significantly from baseline to follow-up (38% vs. 40%). Radiographic signs of bronchial involvement and interstitial lung disease were found in 38% of the patients, respectively. Conclusion Both airway and pulmonary parenchymal disease were commonly found in pSS patients, with a co-existence of both an obstructive and a restrictive pulmonary function pattern, where the latter tended to deteriorate over time. COPD was still a common finding. Airway and pulmonary involvement may be underdiagnosed in pSS, why special attention to clinical assessment of pulmonary involvement in pSS patients is mandated.Objective To determine if a one-year change in walking speed is associated with receiving an incident knee replacement during the following year in adults with and at risk for knee osteoarthritis (OA). Methods Using data from the Osteoarthritis Initiative, we determined a one-year change in 20- meter walk speed from three observation periods (i.e., 0-12, 12-24, and 24-36 month). We operationally defined one-year change in walking speed as either 1) decline 0.1 m/s change. Incident knee replacement was defined using each subsequent one-year period (i.e., 12-24, 24- 36, and 36-48 month). Combining data from the three observation periods, we performed a Poisson regression with robust error variance to determine the relative risk between a change in walking speed (exposure) and incident knee replacement over the following year (outcome). Results Of the 4,264 participants included within this analysis (11,311 total person visits), 115 (3%) adults received a knee replacement. Decline in walking speed was associated with a 104% increase in risk [adjusted relative risk (RR)=2.04; 95% confidence interval (CI)= 1.40-2.98], while an increase in walking speed associated with a 55% decrease in risk (RR=0.45; 95% CI=0.22-0.93) of incident knee replacement in the following year compared to a person with no change in walking speed. Conclusion A one-year decline in walking speed is associated with an increased risk, while one-year increase in walking speed is associated with a decreased risk of future incident knee replacement.Objective Early diagnosis of systemic sclerosis (SSc) is imperative and Raynaud's phenomenon (RP) is an important component of progressive vasculopathy. Nailfold videocapillaroscopy (NVC) is a wellestablished tool that can quantify structural vascular abnormalities. Digital thermal monitoring (DTM) assesses microvascular functional dysfunction related to thermoregulation. In this study, we investigated the correlation of NVC patterns and DTM variables in SSc patients. Methods Patients with SSc by 2013 ACR/EULAR criteria that were consented into the clinical care registry had NVC and DTM performed. For NVC, the number of capillaries (density), measurement of apical diameter (dimension), presence or absence of hemorrhages and number of abnormal shapes were assessed to categorize three different qualitative patterns 'early', 'active' and 'late'. For DTM, Doppler ultrasound hyperemic, low frequency, blood velocity of radial artery and fingertip vascular function was assessed and a vascular reactive index (VRI) measurement was automated. Statistical evaluation was performed by non-parametric tests to assess the correlation of NVC and VRI. Results Thirty-one SSc subjects with interpretable NVC and DTM performed on the same day were included in the study. VRI was progressively higher in SSc patients with the 'early', 'active' and 'late' NVC patterns of microangiopathy (p less then 0.0001). There was a significant negative correlation between VRI and microhemorrhages score (r=-0.363, p=0.044). Conclusion Our study suggests that more advanced vasculopathy correlates to reduced microvascular function as detected by DTM and more advanced structural abnormalities detected by NVC. NVC and DTM may provide different aspects of vasculopathy quantification and complement each other as investigative tools.
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  • Mucositis is a common and feared complication of anticancer therapy that can affect up to 90% of certain populations of patients with cancer. Even seemingly uncomplicated mucositis, which is often self-limited, can result in intense patient discomfort and decline in quality of life. Severe mucositis can be complicated by uncontrolled pain, superinfection or systemic infection, bleeding, and dehydration, and severe mucositis can lead to interruptions or de-escalation in anticancer treatment, resulting in worse oncologic outcomes. This article provides an evidence-based summary to guide practicing oncologists in the assessment, prevention, and management of mucositis induced by chemotherapy, radiotherapy, and targeted therapy.PURPOSE Gender disparity persists in academic medicine. Female faculty are underrepresented in leadership positions and have lower research output. We studied gender differences in faculty rank and departmental leadership and contributing factors among academic hematologists and oncologists in the United States. METHODS For clinical faculty at 146 hematology or oncology fellowship programs listed in the Fellowship and Residency Electronic Interactive Database, we collected data on demographics, academic rank, and research output using the Doximity and Scopus databases. We compared unadjusted characteristics of men and women by using 2-sided t tests and χ2 tests where appropriate. To predict probability of full professorship or leadership position among men versus women, we performed multivariable logistic regression analysis adjusted for clinical experience in years, number of publications, h-index, clinical trial investigator status, National Institutes of Health funding, and workplace ranking (top 20 v not) leadership position.PURPOSE To evaluate physician-reported assessments of an established faculty orientation program for new radiation oncology physicians at a large academic center and to prospectively analyze the effects of an onboarding improvement program based on those assessments. MATERIALS AND METHODS An anonymous survey was designed and distributed to physicians new to the department who received onboarding orientation between 2013 and 2017. Survey questions addressed the comprehensiveness, effectiveness, and utility of various orientation activities. On the basis of the survey results, an improved onboarding program was designed and implemented for nine new faculty members between May 2018 and November 2018. A post-intervention survey querying topics similar to those in the pre-intervention survey was distributed to the new faculty members. Descriptive statistics were generated to compare the pre-intervention and post-intervention groups. RESULTS The overall rate of survey completion was 85% (17 of 20). The intervention program markedly improved physician assessment of comprehensiveness and effectiveness of the onboarding process. Physicians strongly and consistently identified mentor shadowing, on-the-job training, and other faculty mentorship activities as the most important components of an effective onboarding experience. CONCLUSION An enhanced, tailored, person-oriented, formal onboarding improvement program significantly increased physician assessment scores of comprehensiveness and effectiveness of the faculty onboarding process. This model can serve as a framework for increasing physician preparedness, encouraging early physician mentorship, and ensuring a universal standard of quality across large practices.PURPOSE There is a concern that influenza vaccination could increase the incidence of immune-related adverse events (irAEs) in patients with cancer receiving immune checkpoint inhibitors. The aim of our study was to determine the safety of influenza vaccination in this patient population. PATIENTS AND METHODS We retrospectively identified patients who received at least 1 dose of pembrolizumab during any influenza season from September 2014 to August 2017 and reviewed medical records for irAEs. The primary endpoint was the incidence of irAEs. We used multivariable logistic regression and cumulative incidence curve with competing risks for comparison. RESULTS Among 162 patients with cancer included in this study, 70 patients (43.2%) received at least 1 influenza vaccination. The vaccinated group was significantly older (P = .002) and received more cycles of pembrolizumab (P = .006). The incidence of any grade irAEs in the vaccinated group trended toward being lower (25.7% v 40.2%; P = .07) compared with the nonvaccinated group. Influenza vaccination was independently associated with fewer irAEs, with an odds ratio of 0.4 (95% CI, 0.2 to 0.9; P = .03) in multivariable analyses. The vaccinated group was less likely to have irAEs compared with the nonvaccinated group (24.7% v 34.4% at 12 months; P = .05), with death as a competing risk. The median irAE-free duration in the vaccinated group was longer than the nonvaccinated group (not reached v 28 months; P = .037). CONCLUSION Influenza vaccination in patients with cancer receiving immune checkpoint inhibitor therapy was not associated with increased irAEs. This supports the safety of influenza vaccination in this patient population.PURPOSE Inappropriate vancomycin for febrile neutropenia (FN) is an ideal antimicrobial stewardship target. To improve vancomycin prescribing, we instituted a multifaceted intervention, including an educational guideline with audit for compliance; an antibiotic use audit; and an assessment of local burden of methicillin-resistant Staphylococcus aureus (MRSA) colonization and infection. https://www.selleckchem.com/products/chir-124.html MATERIALS AND METHODS We conducted a quasi-experimental pre-post intervention review of vancomycin initiation for FN on a 32-bed hematology/oncology unit. A retrospective chart review was conducted from November 2015 to May 2016 (preintervention period). In January 2017, we implemented an institutional FN guideline emphasizing criteria for appropriate use. Vancomycin audit was conducted from February 2017 to October 2017 (postintervention period). The primary outcome was appropriateness of vancomycin initiation. We then compared average antibiotic use (days of therapy per 1,000 patient days) for vancomycin and cefepime before and after intervention.
    Mucositis is a common and feared complication of anticancer therapy that can affect up to 90% of certain populations of patients with cancer. Even seemingly uncomplicated mucositis, which is often self-limited, can result in intense patient discomfort and decline in quality of life. Severe mucositis can be complicated by uncontrolled pain, superinfection or systemic infection, bleeding, and dehydration, and severe mucositis can lead to interruptions or de-escalation in anticancer treatment, resulting in worse oncologic outcomes. This article provides an evidence-based summary to guide practicing oncologists in the assessment, prevention, and management of mucositis induced by chemotherapy, radiotherapy, and targeted therapy.PURPOSE Gender disparity persists in academic medicine. Female faculty are underrepresented in leadership positions and have lower research output. We studied gender differences in faculty rank and departmental leadership and contributing factors among academic hematologists and oncologists in the United States. METHODS For clinical faculty at 146 hematology or oncology fellowship programs listed in the Fellowship and Residency Electronic Interactive Database, we collected data on demographics, academic rank, and research output using the Doximity and Scopus databases. We compared unadjusted characteristics of men and women by using 2-sided t tests and χ2 tests where appropriate. To predict probability of full professorship or leadership position among men versus women, we performed multivariable logistic regression analysis adjusted for clinical experience in years, number of publications, h-index, clinical trial investigator status, National Institutes of Health funding, and workplace ranking (top 20 v not) leadership position.PURPOSE To evaluate physician-reported assessments of an established faculty orientation program for new radiation oncology physicians at a large academic center and to prospectively analyze the effects of an onboarding improvement program based on those assessments. MATERIALS AND METHODS An anonymous survey was designed and distributed to physicians new to the department who received onboarding orientation between 2013 and 2017. Survey questions addressed the comprehensiveness, effectiveness, and utility of various orientation activities. On the basis of the survey results, an improved onboarding program was designed and implemented for nine new faculty members between May 2018 and November 2018. A post-intervention survey querying topics similar to those in the pre-intervention survey was distributed to the new faculty members. Descriptive statistics were generated to compare the pre-intervention and post-intervention groups. RESULTS The overall rate of survey completion was 85% (17 of 20). The intervention program markedly improved physician assessment of comprehensiveness and effectiveness of the onboarding process. Physicians strongly and consistently identified mentor shadowing, on-the-job training, and other faculty mentorship activities as the most important components of an effective onboarding experience. CONCLUSION An enhanced, tailored, person-oriented, formal onboarding improvement program significantly increased physician assessment scores of comprehensiveness and effectiveness of the faculty onboarding process. This model can serve as a framework for increasing physician preparedness, encouraging early physician mentorship, and ensuring a universal standard of quality across large practices.PURPOSE There is a concern that influenza vaccination could increase the incidence of immune-related adverse events (irAEs) in patients with cancer receiving immune checkpoint inhibitors. The aim of our study was to determine the safety of influenza vaccination in this patient population. PATIENTS AND METHODS We retrospectively identified patients who received at least 1 dose of pembrolizumab during any influenza season from September 2014 to August 2017 and reviewed medical records for irAEs. The primary endpoint was the incidence of irAEs. We used multivariable logistic regression and cumulative incidence curve with competing risks for comparison. RESULTS Among 162 patients with cancer included in this study, 70 patients (43.2%) received at least 1 influenza vaccination. The vaccinated group was significantly older (P = .002) and received more cycles of pembrolizumab (P = .006). The incidence of any grade irAEs in the vaccinated group trended toward being lower (25.7% v 40.2%; P = .07) compared with the nonvaccinated group. Influenza vaccination was independently associated with fewer irAEs, with an odds ratio of 0.4 (95% CI, 0.2 to 0.9; P = .03) in multivariable analyses. The vaccinated group was less likely to have irAEs compared with the nonvaccinated group (24.7% v 34.4% at 12 months; P = .05), with death as a competing risk. The median irAE-free duration in the vaccinated group was longer than the nonvaccinated group (not reached v 28 months; P = .037). CONCLUSION Influenza vaccination in patients with cancer receiving immune checkpoint inhibitor therapy was not associated with increased irAEs. This supports the safety of influenza vaccination in this patient population.PURPOSE Inappropriate vancomycin for febrile neutropenia (FN) is an ideal antimicrobial stewardship target. To improve vancomycin prescribing, we instituted a multifaceted intervention, including an educational guideline with audit for compliance; an antibiotic use audit; and an assessment of local burden of methicillin-resistant Staphylococcus aureus (MRSA) colonization and infection. https://www.selleckchem.com/products/chir-124.html MATERIALS AND METHODS We conducted a quasi-experimental pre-post intervention review of vancomycin initiation for FN on a 32-bed hematology/oncology unit. A retrospective chart review was conducted from November 2015 to May 2016 (preintervention period). In January 2017, we implemented an institutional FN guideline emphasizing criteria for appropriate use. Vancomycin audit was conducted from February 2017 to October 2017 (postintervention period). The primary outcome was appropriateness of vancomycin initiation. We then compared average antibiotic use (days of therapy per 1,000 patient days) for vancomycin and cefepime before and after intervention.
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  • Chlorpheniramine is a pharmaceutical widely used and found in water environments. Besides hormone disruption and adverse environmental effects, chlorpheniramine forms carcinogenic nitrosamines during disinfection. We have demonstrated previously the efficient adsorption of chlorpheniramine from aqueous solution onto graphene oxide-magnetite composite (GO-Fe3O4). The present study focused on the elimination of chlorpheniramine and the formation of nitrosamine byproducts during reaction with H2O2 over GO-Fe3O4 catalyst. The effects of the morphology of GO-Fe3O4 in terms of iron fraction, pH, concentrations of H2O2 and organic matters on chlorpheniramine removal in the GO-Fe3O4-H2O2 system were investigated. Chlorpheniramine was efficiently removed at pH 9 when GO-Fe3O4 had a higher micropore volume and surface area. Kinetics study showed that both oxidation (k = 5.1(±0.2) × 10-3 (mg g-1)-1 min-1) and adsorption reactions (k = 2.7(±0.1) × 10-3 (mg g-1)-1 min-1) fitted well with the second-order kinetics model. The adsorption sites on the GO-Fe3O4 surface could be different from those involved during catalytic oxidation. Chlorpheniramine removal decreased by 44.9% in the 5th cycle without regeneration due to the structural fracture of GO-Fe3O4. A tentative pathway of chlorpheniramine degradation and nitrosamine formation by GO-Fe3O4-H2O2 was proposed. GO-Fe3O4 was an adsorbent and effective catalyst in chlorpheniramine degradation by H2O2 that exhibited limited nitrosamine formation at moderate reaction time.As far as the authors know, no in-depth comparison has been made between the different performances of the solar photo-Fenton process for the removal of contaminants of emerging concern (CECs) as a function of pH. To this end, real WWTP secondary effluents were treated in continuous flow mode at pilot plant scale. The effect of hydraulic residence time (HRT), liquid depth and percentage of CEC removal on treatment capacity was studied. At acidic pH (2.8), the iron source was FeSO4 and at neutral pH (7.0), it was Fe(III)-EDDS. At both pH values, 2250 L m-2 d-1 can be treated in 15-cm deep raceway pond reactors at 30 min HRT with 0.1 mM iron and 0.88 mM H2O2 in order to achieve 80% CEC removal. https://www.selleckchem.com/products/sgc707.html Treatment costs were 0.25 € m-3 and 0.56 € m-3 at acidic and neutral pH, respectively. This study paves the way for the solar photo-Fenton process to be employed on a commercial scale.A father's lifetime experience is a major risk factor for a range of diseases in an individual, and the consequences of the exposure can also be transmitted to his offspring. Our previous work has demonstrated that damage to testicular structures and decline in sperm quality in male **** can be caused by microcystin-leucine arginine (**-LR), but the overall effects of the scope and extent of paternal exposure on health and disease in the offspring remain underexplored. Here, we report that **-LR-paternal-exposed offspring **** showed reduced litter size and body weight accompanied by increased abnormalities in the lung. Analyses of the small noncoding RNAs (sncRNAs) in the sperm from **-LR-exposed males demonstrated the downregulation of a wide range of piRNAs enriched for those target genes involved in the regulation of the embryo implantation pathways. Gene and protein expression analyses, as well as biochemical and functional studies, revealed suppressed expression of Hsp90α in testicular tissues from **-LR-exposed males. Decreased Hsp90α in testicular tissues impaired the development of the offspring. In this study, we revealed that **-LR alters the expression of Hsp90α in testicular tissues to cause changes in the expression profiles of sperm piRNAs produced by paternal ****. These changes lead to aberrant activation of the Wnt/β-catenin signaling pathway in pulmonary tissues of offspring ****, causing lung tissue damage and abnormal development. We hereby confirmed that **-LR-induced alterations in epigenetic inheritance are capable of contributing to intergenerational developmental defects in paternal-exposed offspring ****.It is essential to know the environmental parameters within which the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can survive to understand its global dispersal pattern. We found that 60.0% of the confirmed cases of coronavirus disease 2019 (COVID-19) occurred in places where the air temperature ranged from 5 °C to 15 °C, with a peak in cases at 11.54 °C. Moreover, approximately 73.8% of the confirmed cases were concentrated in regions with absolute humidity of 3 g/m3 to 10 g/m3. SARS-CoV-2 appears to be spreading toward higher latitudes. Our findings suggest that there is an optimal climatic zone in which the concentration of SARS-CoV-2 markedly increases in the ambient environment (including the surfaces of objects). These results strongly imply that the COVID-19 pandemic may spread cyclically and outbreaks may recur in large cities in the mid-latitudes in autumn 2020.Naphthalene, a naturally-occurring polyaromatic hydrocarbon, pose potential threats to health for its wide exposures in environment. Naphthalene could disrupt the redox equilibrium resulting in oxidative damage. Antioxidant enzymes catalase (CAT) and superoxide dismutase (***) are considered to be the efficient defense barriers to protect organisms from negative impacts of toxicants. Limited information is available regarding the underlying molecular mechanism between antioxidant enzymes and naphthalene. In this paper, structural and functional alterations of CAT and *** for low dose (1.6-25.6 mg/L) naphthalene exposure have been investigated at the molecular and cellular levels. The enzyme activity responses of CAT and *** in hepatocytes for naphthalene were consistent with the molecular, in which the activity of CAT increased and the activity of *** slightly inhibited. Spectroscopy methods and molecular docking were carried out to investigate the underlying binding mechanisms. Naphthalene exposure significantly changed the conformation of CAT with secondary structure alteration (α-helix increase) but only changed the skeleton structure of *** without secondary structure alteration. Naphthalene could bind to CAT and *** primarily via H-binding force accompanied with the particle size of CAT/*** agglomerates decreasing. Naphthalene preferentially bound to the surface of CAT and ***. Besides, naphthalene could also bind directly to the active center of CAT with the key residues Arg364 and Tyr 357 for activity. This paper provides a combined cellular and molecular strategy to research biomarker responses for toxicants exposure. Besides, this study offers detailed basic data for the comprehensive understanding of naphthalene toxicity.
    Chlorpheniramine is a pharmaceutical widely used and found in water environments. Besides hormone disruption and adverse environmental effects, chlorpheniramine forms carcinogenic nitrosamines during disinfection. We have demonstrated previously the efficient adsorption of chlorpheniramine from aqueous solution onto graphene oxide-magnetite composite (GO-Fe3O4). The present study focused on the elimination of chlorpheniramine and the formation of nitrosamine byproducts during reaction with H2O2 over GO-Fe3O4 catalyst. The effects of the morphology of GO-Fe3O4 in terms of iron fraction, pH, concentrations of H2O2 and organic matters on chlorpheniramine removal in the GO-Fe3O4-H2O2 system were investigated. Chlorpheniramine was efficiently removed at pH 9 when GO-Fe3O4 had a higher micropore volume and surface area. Kinetics study showed that both oxidation (k = 5.1(±0.2) × 10-3 (mg g-1)-1 min-1) and adsorption reactions (k = 2.7(±0.1) × 10-3 (mg g-1)-1 min-1) fitted well with the second-order kinetics model. The adsorption sites on the GO-Fe3O4 surface could be different from those involved during catalytic oxidation. Chlorpheniramine removal decreased by 44.9% in the 5th cycle without regeneration due to the structural fracture of GO-Fe3O4. A tentative pathway of chlorpheniramine degradation and nitrosamine formation by GO-Fe3O4-H2O2 was proposed. GO-Fe3O4 was an adsorbent and effective catalyst in chlorpheniramine degradation by H2O2 that exhibited limited nitrosamine formation at moderate reaction time.As far as the authors know, no in-depth comparison has been made between the different performances of the solar photo-Fenton process for the removal of contaminants of emerging concern (CECs) as a function of pH. To this end, real WWTP secondary effluents were treated in continuous flow mode at pilot plant scale. The effect of hydraulic residence time (HRT), liquid depth and percentage of CEC removal on treatment capacity was studied. At acidic pH (2.8), the iron source was FeSO4 and at neutral pH (7.0), it was Fe(III)-EDDS. At both pH values, 2250 L m-2 d-1 can be treated in 15-cm deep raceway pond reactors at 30 min HRT with 0.1 mM iron and 0.88 mM H2O2 in order to achieve 80% CEC removal. https://www.selleckchem.com/products/sgc707.html Treatment costs were 0.25 € m-3 and 0.56 € m-3 at acidic and neutral pH, respectively. This study paves the way for the solar photo-Fenton process to be employed on a commercial scale.A father's lifetime experience is a major risk factor for a range of diseases in an individual, and the consequences of the exposure can also be transmitted to his offspring. Our previous work has demonstrated that damage to testicular structures and decline in sperm quality in male mice can be caused by microcystin-leucine arginine (MC-LR), but the overall effects of the scope and extent of paternal exposure on health and disease in the offspring remain underexplored. Here, we report that MC-LR-paternal-exposed offspring mice showed reduced litter size and body weight accompanied by increased abnormalities in the lung. Analyses of the small noncoding RNAs (sncRNAs) in the sperm from MC-LR-exposed males demonstrated the downregulation of a wide range of piRNAs enriched for those target genes involved in the regulation of the embryo implantation pathways. Gene and protein expression analyses, as well as biochemical and functional studies, revealed suppressed expression of Hsp90α in testicular tissues from MC-LR-exposed males. Decreased Hsp90α in testicular tissues impaired the development of the offspring. In this study, we revealed that MC-LR alters the expression of Hsp90α in testicular tissues to cause changes in the expression profiles of sperm piRNAs produced by paternal mice. These changes lead to aberrant activation of the Wnt/β-catenin signaling pathway in pulmonary tissues of offspring mice, causing lung tissue damage and abnormal development. We hereby confirmed that MC-LR-induced alterations in epigenetic inheritance are capable of contributing to intergenerational developmental defects in paternal-exposed offspring mice.It is essential to know the environmental parameters within which the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can survive to understand its global dispersal pattern. We found that 60.0% of the confirmed cases of coronavirus disease 2019 (COVID-19) occurred in places where the air temperature ranged from 5 °C to 15 °C, with a peak in cases at 11.54 °C. Moreover, approximately 73.8% of the confirmed cases were concentrated in regions with absolute humidity of 3 g/m3 to 10 g/m3. SARS-CoV-2 appears to be spreading toward higher latitudes. Our findings suggest that there is an optimal climatic zone in which the concentration of SARS-CoV-2 markedly increases in the ambient environment (including the surfaces of objects). These results strongly imply that the COVID-19 pandemic may spread cyclically and outbreaks may recur in large cities in the mid-latitudes in autumn 2020.Naphthalene, a naturally-occurring polyaromatic hydrocarbon, pose potential threats to health for its wide exposures in environment. Naphthalene could disrupt the redox equilibrium resulting in oxidative damage. Antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD) are considered to be the efficient defense barriers to protect organisms from negative impacts of toxicants. Limited information is available regarding the underlying molecular mechanism between antioxidant enzymes and naphthalene. In this paper, structural and functional alterations of CAT and SOD for low dose (1.6-25.6 mg/L) naphthalene exposure have been investigated at the molecular and cellular levels. The enzyme activity responses of CAT and SOD in hepatocytes for naphthalene were consistent with the molecular, in which the activity of CAT increased and the activity of SOD slightly inhibited. Spectroscopy methods and molecular docking were carried out to investigate the underlying binding mechanisms. Naphthalene exposure significantly changed the conformation of CAT with secondary structure alteration (α-helix increase) but only changed the skeleton structure of SOD without secondary structure alteration. Naphthalene could bind to CAT and SOD primarily via H-binding force accompanied with the particle size of CAT/SOD agglomerates decreasing. Naphthalene preferentially bound to the surface of CAT and SOD. Besides, naphthalene could also bind directly to the active center of CAT with the key residues Arg364 and Tyr 357 for activity. This paper provides a combined cellular and molecular strategy to research biomarker responses for toxicants exposure. Besides, this study offers detailed basic data for the comprehensive understanding of naphthalene toxicity.
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  • umer expectations.Insulin resistance (IR) disrupts ovarian functions in polycystic ovary syndrome (PCOS). The contributing factors remains elusive. High mobility group box 1 (HMGB1), a damage-associated molecular pattern molecule, has been shown to be related to IR and autophagy, respectively, in peripheral tissues. Here, we investigated whether increased HMGB1 contributes to IR in granulosa cells of PCOS patients via induction of aberrant autophagy. Results showed that HMGB1 abundance in the follicular fluid was significantly increased with enhanced autophagy in granulosa cells in PCOS patients with IR. HMGB1 exacerbated autophagy in granulosa cells as evinced by increased LC3B II/I ratio and ATG7 as well as decreased p62, the markers for autophagy. Concurrently, HMGB1 impaired insulin sensitivities by attenuating the abundance of insulin receptor substrate-1, Akt phosphorylation, GLUT4 translocation, and glucose uptake in granulosa cells, which were reversed by blocking autophagy pathways with siRNA-mediated knockdown of ATG7 or with chloroquine and bafilomycin A1, the lysosome inhibitors. In conclusion, our results indicate that increased HMGB1 contributes to IR development in granulosa cells of PCOS patients, which is associated with exacerbation of autophagy by HMGB1. Control of HMGB1 production may be benefical for the improvement of insulin sensitivity in granulosa cells in PCOS.Background Antitachycardia pacing (ATP), which may avoid unnecessary implantable cardioverter-defibrillator (ICD) shocks, does not always terminate ventricular arrhythmias (VAs). Mean entropy calculated using cardiac magnetic resonance texture analysis (CMR-TA) has been shown to predict appropriate ICD therapy. https://www.selleckchem.com/products/abc294640.html We examined whether scar heterogeneity, quantified by mean entropy, is associated with ATP failure and explore potential mechanisms using computer modeling. Methods A subanalysis of 114 patients undergoing CMR-TA where the primary endpoint was delivery of appropriate ICD therapy (ATP or shock therapy) was performed. Patients receiving appropriate ICD therapy (n = 33) were dichotomized into "successful ATP" versus "shock therapy" groups. In silico computer modeling was used to explore underlying mechanisms. Results A total of 16 of 33 (48.5%) patients had successful ATP to terminate VA, and 17 of 33 (51.5%) patients required shock therapy. Mean entropy was significantly higher in the shock versus successful ATP group (6.1 ± 0.5 vs 5.5 ± 0.7, P = .037). Analysis of patients receiving ATP (n = 22) showed significantly higher mean entropy in the six of 22 patients that failed ATP (followed by rescue ICD shock) compared to 16 of 22 that had successful ATP (6.3 ± 0.7 vs 5.5 ± 0.7, P = .048). Computer modeling suggested inability of the paced wavefront in ATP to successfully propagate from the electrode site through patchy fibrosis as a possible mechanism of failed ATP. Conclusions Our findings suggest lower scar heterogeneity (mean entropy) is associated with successful ATP, whereas higher scar heterogeneity is associated with more aggressive VAs unresponsive to ATP requiring shock therapy that may be due to inability of the paced wavefront to propagate through scar and terminate the VA circuit.Objective To investigate the impact of high-fidelity simulation on nursing students' knowledge, critical thinking, and clinical decision-making in the management of pre-eclampsia, and to explore the students' views and learning experiences. Methods A mixed-methods design study was conducted on 107 third-year nursing students. The students were randomly assigned to the control group (n=54) or the experimental group (n=53). The students in the experimental group attended the simulation training using a high-fidelity simulator, while the students in the control group attended only the classical training on "the management of pre-eclampsia." Results Knowledge (P less then 0.001), critical thinking (P less then 0.05), and clinical decision-making (P less then 0.05) scores of students in the experimental group increased after the simulation. In the focus group interviews, five themes were identified learning development; closing the gap between theory and practice; confident decision-making and self-confidence; professional preparation; and recommendations. Conclusion High-fidelity simulation is efficacious for improving the management of pre-eclampsia among nursing students.Carfilzomib has been associated with the development of thrombotic microangiopathy (TMA) in relapsed/refractory multiple myeloma patients, a severe disease with no currently available aetiological treatment. We evaluated the potential role of terminal complement pathway in four patients with carfilzomib-induced TMA. Membrane attack complex (C5b-9) deposition on endothelial cells in culture exposed to plasma from patients during the acute phase of the disease suggests complement overactivation as a mechanism of potential endothelial damage in three out of four patients. If confirmed in larger cohorts, C5b-9 evaluation will allow early identification of patients who could benefit from complement blockade and treatment monitoring.Background Significant racial differences have been observed in the incidence and clinical outcomes of diffuse large B-cell lymphoma (DLBCL) in the United States, but to the authors' knowledge it remains unclear whether genomic differences contribute to these disparities. Methods To understand the influences of genetic ancestry on tumor genomic alterations, the authors estimated the genetic ancestry of 1001 previously described patients with DLBCL using unsupervised model-based Admixture global ancestry analysis applied to exome sequencing data and examined the mutational profile of 150 DLBCL driver genes in tumors obtained from this cohort. Results Global ancestry prediction identified 619 patients with >90% European ancestry, 81 patients with >90% African ancestry, and 50 patients with >90% Asian ancestry. Compared with patients with DLBCL with European ancestry, patients with African ancestry were aged >10 years younger at the time of diagnosis and were more likely to present with B symptoms, elevated serum lactate dehydrogenase, extranodal disease, and advanced stage disease.
    umer expectations.Insulin resistance (IR) disrupts ovarian functions in polycystic ovary syndrome (PCOS). The contributing factors remains elusive. High mobility group box 1 (HMGB1), a damage-associated molecular pattern molecule, has been shown to be related to IR and autophagy, respectively, in peripheral tissues. Here, we investigated whether increased HMGB1 contributes to IR in granulosa cells of PCOS patients via induction of aberrant autophagy. Results showed that HMGB1 abundance in the follicular fluid was significantly increased with enhanced autophagy in granulosa cells in PCOS patients with IR. HMGB1 exacerbated autophagy in granulosa cells as evinced by increased LC3B II/I ratio and ATG7 as well as decreased p62, the markers for autophagy. Concurrently, HMGB1 impaired insulin sensitivities by attenuating the abundance of insulin receptor substrate-1, Akt phosphorylation, GLUT4 translocation, and glucose uptake in granulosa cells, which were reversed by blocking autophagy pathways with siRNA-mediated knockdown of ATG7 or with chloroquine and bafilomycin A1, the lysosome inhibitors. In conclusion, our results indicate that increased HMGB1 contributes to IR development in granulosa cells of PCOS patients, which is associated with exacerbation of autophagy by HMGB1. Control of HMGB1 production may be benefical for the improvement of insulin sensitivity in granulosa cells in PCOS.Background Antitachycardia pacing (ATP), which may avoid unnecessary implantable cardioverter-defibrillator (ICD) shocks, does not always terminate ventricular arrhythmias (VAs). Mean entropy calculated using cardiac magnetic resonance texture analysis (CMR-TA) has been shown to predict appropriate ICD therapy. https://www.selleckchem.com/products/abc294640.html We examined whether scar heterogeneity, quantified by mean entropy, is associated with ATP failure and explore potential mechanisms using computer modeling. Methods A subanalysis of 114 patients undergoing CMR-TA where the primary endpoint was delivery of appropriate ICD therapy (ATP or shock therapy) was performed. Patients receiving appropriate ICD therapy (n = 33) were dichotomized into "successful ATP" versus "shock therapy" groups. In silico computer modeling was used to explore underlying mechanisms. Results A total of 16 of 33 (48.5%) patients had successful ATP to terminate VA, and 17 of 33 (51.5%) patients required shock therapy. Mean entropy was significantly higher in the shock versus successful ATP group (6.1 ± 0.5 vs 5.5 ± 0.7, P = .037). Analysis of patients receiving ATP (n = 22) showed significantly higher mean entropy in the six of 22 patients that failed ATP (followed by rescue ICD shock) compared to 16 of 22 that had successful ATP (6.3 ± 0.7 vs 5.5 ± 0.7, P = .048). Computer modeling suggested inability of the paced wavefront in ATP to successfully propagate from the electrode site through patchy fibrosis as a possible mechanism of failed ATP. Conclusions Our findings suggest lower scar heterogeneity (mean entropy) is associated with successful ATP, whereas higher scar heterogeneity is associated with more aggressive VAs unresponsive to ATP requiring shock therapy that may be due to inability of the paced wavefront to propagate through scar and terminate the VA circuit.Objective To investigate the impact of high-fidelity simulation on nursing students' knowledge, critical thinking, and clinical decision-making in the management of pre-eclampsia, and to explore the students' views and learning experiences. Methods A mixed-methods design study was conducted on 107 third-year nursing students. The students were randomly assigned to the control group (n=54) or the experimental group (n=53). The students in the experimental group attended the simulation training using a high-fidelity simulator, while the students in the control group attended only the classical training on "the management of pre-eclampsia." Results Knowledge (P less then 0.001), critical thinking (P less then 0.05), and clinical decision-making (P less then 0.05) scores of students in the experimental group increased after the simulation. In the focus group interviews, five themes were identified learning development; closing the gap between theory and practice; confident decision-making and self-confidence; professional preparation; and recommendations. Conclusion High-fidelity simulation is efficacious for improving the management of pre-eclampsia among nursing students.Carfilzomib has been associated with the development of thrombotic microangiopathy (TMA) in relapsed/refractory multiple myeloma patients, a severe disease with no currently available aetiological treatment. We evaluated the potential role of terminal complement pathway in four patients with carfilzomib-induced TMA. Membrane attack complex (C5b-9) deposition on endothelial cells in culture exposed to plasma from patients during the acute phase of the disease suggests complement overactivation as a mechanism of potential endothelial damage in three out of four patients. If confirmed in larger cohorts, C5b-9 evaluation will allow early identification of patients who could benefit from complement blockade and treatment monitoring.Background Significant racial differences have been observed in the incidence and clinical outcomes of diffuse large B-cell lymphoma (DLBCL) in the United States, but to the authors' knowledge it remains unclear whether genomic differences contribute to these disparities. Methods To understand the influences of genetic ancestry on tumor genomic alterations, the authors estimated the genetic ancestry of 1001 previously described patients with DLBCL using unsupervised model-based Admixture global ancestry analysis applied to exome sequencing data and examined the mutational profile of 150 DLBCL driver genes in tumors obtained from this cohort. Results Global ancestry prediction identified 619 patients with >90% European ancestry, 81 patients with >90% African ancestry, and 50 patients with >90% Asian ancestry. Compared with patients with DLBCL with European ancestry, patients with African ancestry were aged >10 years younger at the time of diagnosis and were more likely to present with B symptoms, elevated serum lactate dehydrogenase, extranodal disease, and advanced stage disease.
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  • The transition to university can be stressful for first-year university students. Despite the fact where the feeling of worry is a shared symptom by various mental health issues, there is a lack of studies that investigate into this matter. As worry is a domain-specific construct, there is a need for a valid and reliable measure of worry specifically for university students. Hence, this study aimed to evaluate the psychometric properties of the Student Worry Scale (SWS), particularly in terms of its validity and reliability. For this purpose, the current study recruited a sample of 295 first-year students to evaluate the psychometric properties of SWS. Exploratory factor analysis yielded a five-factor structure of SWS, which explained 55.7% of the total variance. The yielded five factors were general worries, financial-related concerns, significant other's well-being, academic concerns, and social adequacy concerns. Inter-correlations between the five factors were all significant (r ranged between 0.395 and 0.625). The SWS demonstrated good internal consistency in this study (Cronbach's alpha ranged between 0.786 and 0.941). Overall, the SWS is psychometrically evidenced to be a reliable and valid content-based worry measure specifically for university students. © 2020 Scandinavian Psychological Associations and John Wiley & Sons Ltd.Despite recent advances, gender inequality persists in many scientific fields including medicine. Thus far, no study has extensively analyzed the gender composition of contemporary researchers in the oncology field. We examined 40 oncological journals (Web of Science, Oncology category) with different impact factors (Q1-Q4) and extracted all the articles and reviews published during 2015-2017 in order to identify the gender of their authors. Our data showed that women represent about 38% of all the authorships, both in articles and reviews. In relative terms, women are overrepresented as first authors of articles (43.8%), and clearly underrepresented as last or senior authors ( less then 30%). This double pattern, also observed in other medical fields, suggests that age, or more specifically, seniority, may play some role in the gender composition of cancer researchers. Examining the pattern of collaboration, an interesting finding was observed the articles signed by a woman in the first or in the last position roughly showed gender parity in the byline. We also found some differences in the content of the articles depending on which gender occupies the first and last positions of the authorships. © 2020 UICC.BACKGROUND In experimental canine septic shock, depressed circulating granulocyte counts were associated with a poor outcome and increasing counts with prophylactic granulocyte colony-stimulating factor (G-CSF) improved outcome. Therapeutic G-CSF, in contrast, did not improve circulating counts or outcome, and therefore investigation was undertaken to determine whether transfusing granulocytes therapeutically would improve outcome. STUDY DESIGN AND METHODS Twenty-eight purpose-bred beagles underwent an intrabronchial Staphylococcus aureus challenge and 4 hours later were randomly assigned to granulocyte (40-100 × 109 cells) or plasma transfusion. RESULTS Granulocyte transfusion significantly expanded the low circulating counts for hours compared to septic controls but was not associated with significant mortality benefit (1/14, 7% vs. 2/14, 14%, respectively; p = 0.29). Septic animals with higher granulocyte count at 4 hours (median [interquartile range] of 3.81 3.39-5.05] vs. 1.77 [1.25-2.50]) had significantly increased survival independent of whether they were transfused with granulocytes. In a subgroup analysis, animals with higher circulating granulocyte counts receiving donor granulocytes had worsened lung injury compared to septic controls. Conversely, donor granulocytes decreased lung injury in septic animals with lower counts. CONCLUSION During bacterial pneumonia, circulating counts predict the outcome of transfusing granulocytes. With low but normal counts, transfusing granulocytes does not improve survival and injures the lung, whereas for animals with very low counts, but not absolute neutropenia, granulocyte transfusion improves lung function. Published 2020. This article is a U.S. Government work and is in the public domain in the USA.Alcohol-associated liver disease (ALD) is a common chronic liver disease worldwide with high morbidity and mortality, and no FDA-approved therapies. Fructose (dietary or endogenous), its metabolite uric acid, and aldose reductase (AR, the only endogenous enzyme that produces fructose) are strongly associated with the development of non-alcoholic fatty liver disease (NAFLD). However, the role of AR or its metabolites in ALD remains understudied and was examined using human specimens, cultured cells and mouse model systems. We demonstrated for the first time in liver specimens from alcoholic hepatitis (AH) patients, AR upregulation and elevated AR metabolites (sorbitol, fructose, and uric acid) which correlated significantly with (i) increased lipid peroxidation byproducts and ER stress, (ii) decreased protective ER chaperones, and (iii) greater cell death and liver injury. Further, we established a causal role for AR in ALD by showing that the genetic deficiency of AR (knockout ****) prevented alcohol-induced increase in harmful AR metabolites, toxic aldehydes, steatosis, ER stress, apoptosis and liver injury. Lastly, we demonstrated the therapeutic potential of pharmacological AR inhibition against alcohol-induced hepatic injury in experimental ALD CONCLUSIONS Our data demonstrate that hepatic AR upregulation, and consequent elevation in fructose, sorbitol and/or uric acid, are important factors contributing to alcohol-induced steatosis, ER stress, apoptosis and liver injury in both experimental and human ALD. Our study provides a strong rationale to evaluate AR as a potential therapeutic target and to test AR inhibitors to ameliorate alcohol-induced liver injury. https://www.selleckchem.com/products/Cediranib.html This article is protected by copyright. All rights reserved.PURPOSE Water equivalent diameter (WED) is a robust patient-size descriptor. Localizer-based WED estimation is less sensitive to truncation errors resulting from limited field of view, and produces WED estimates at different locations within one localizer radiograph, prior to the initiation of axial scans. This method is considered difficult to implement by the clinical community due to the necessary calibration between localizer pixel values and attenuation, and the unknown stability of calibration results across scanners and over time. We investigated the stability of calibration results across 25 CT scanners from 3 medical centers, and their stability over 3~29 months for 14 of those scanners. METHODS Localizer and axial images of ACR and body CTDI phantoms were acquired, using routine clinical techniques (120kV and lateral localizers) on each of the 25 CT scanners 8 GE scanners (CT750HD, VCT, and Revolution), 8 Siemens scanners (Definition AS, Force, Flash, and Edge), 5 Canon scanners (Aquilion-One, Aquilion-Prime80, and Aquilion-64), and 4 Philips scanners (iCT 256, iQon, and Ingenuity).
    The transition to university can be stressful for first-year university students. Despite the fact where the feeling of worry is a shared symptom by various mental health issues, there is a lack of studies that investigate into this matter. As worry is a domain-specific construct, there is a need for a valid and reliable measure of worry specifically for university students. Hence, this study aimed to evaluate the psychometric properties of the Student Worry Scale (SWS), particularly in terms of its validity and reliability. For this purpose, the current study recruited a sample of 295 first-year students to evaluate the psychometric properties of SWS. Exploratory factor analysis yielded a five-factor structure of SWS, which explained 55.7% of the total variance. The yielded five factors were general worries, financial-related concerns, significant other's well-being, academic concerns, and social adequacy concerns. Inter-correlations between the five factors were all significant (r ranged between 0.395 and 0.625). The SWS demonstrated good internal consistency in this study (Cronbach's alpha ranged between 0.786 and 0.941). Overall, the SWS is psychometrically evidenced to be a reliable and valid content-based worry measure specifically for university students. © 2020 Scandinavian Psychological Associations and John Wiley & Sons Ltd.Despite recent advances, gender inequality persists in many scientific fields including medicine. Thus far, no study has extensively analyzed the gender composition of contemporary researchers in the oncology field. We examined 40 oncological journals (Web of Science, Oncology category) with different impact factors (Q1-Q4) and extracted all the articles and reviews published during 2015-2017 in order to identify the gender of their authors. Our data showed that women represent about 38% of all the authorships, both in articles and reviews. In relative terms, women are overrepresented as first authors of articles (43.8%), and clearly underrepresented as last or senior authors ( less then 30%). This double pattern, also observed in other medical fields, suggests that age, or more specifically, seniority, may play some role in the gender composition of cancer researchers. Examining the pattern of collaboration, an interesting finding was observed the articles signed by a woman in the first or in the last position roughly showed gender parity in the byline. We also found some differences in the content of the articles depending on which gender occupies the first and last positions of the authorships. © 2020 UICC.BACKGROUND In experimental canine septic shock, depressed circulating granulocyte counts were associated with a poor outcome and increasing counts with prophylactic granulocyte colony-stimulating factor (G-CSF) improved outcome. Therapeutic G-CSF, in contrast, did not improve circulating counts or outcome, and therefore investigation was undertaken to determine whether transfusing granulocytes therapeutically would improve outcome. STUDY DESIGN AND METHODS Twenty-eight purpose-bred beagles underwent an intrabronchial Staphylococcus aureus challenge and 4 hours later were randomly assigned to granulocyte (40-100 × 109 cells) or plasma transfusion. RESULTS Granulocyte transfusion significantly expanded the low circulating counts for hours compared to septic controls but was not associated with significant mortality benefit (1/14, 7% vs. 2/14, 14%, respectively; p = 0.29). Septic animals with higher granulocyte count at 4 hours (median [interquartile range] of 3.81 3.39-5.05] vs. 1.77 [1.25-2.50]) had significantly increased survival independent of whether they were transfused with granulocytes. In a subgroup analysis, animals with higher circulating granulocyte counts receiving donor granulocytes had worsened lung injury compared to septic controls. Conversely, donor granulocytes decreased lung injury in septic animals with lower counts. CONCLUSION During bacterial pneumonia, circulating counts predict the outcome of transfusing granulocytes. With low but normal counts, transfusing granulocytes does not improve survival and injures the lung, whereas for animals with very low counts, but not absolute neutropenia, granulocyte transfusion improves lung function. Published 2020. This article is a U.S. Government work and is in the public domain in the USA.Alcohol-associated liver disease (ALD) is a common chronic liver disease worldwide with high morbidity and mortality, and no FDA-approved therapies. Fructose (dietary or endogenous), its metabolite uric acid, and aldose reductase (AR, the only endogenous enzyme that produces fructose) are strongly associated with the development of non-alcoholic fatty liver disease (NAFLD). However, the role of AR or its metabolites in ALD remains understudied and was examined using human specimens, cultured cells and mouse model systems. We demonstrated for the first time in liver specimens from alcoholic hepatitis (AH) patients, AR upregulation and elevated AR metabolites (sorbitol, fructose, and uric acid) which correlated significantly with (i) increased lipid peroxidation byproducts and ER stress, (ii) decreased protective ER chaperones, and (iii) greater cell death and liver injury. Further, we established a causal role for AR in ALD by showing that the genetic deficiency of AR (knockout mice) prevented alcohol-induced increase in harmful AR metabolites, toxic aldehydes, steatosis, ER stress, apoptosis and liver injury. Lastly, we demonstrated the therapeutic potential of pharmacological AR inhibition against alcohol-induced hepatic injury in experimental ALD CONCLUSIONS Our data demonstrate that hepatic AR upregulation, and consequent elevation in fructose, sorbitol and/or uric acid, are important factors contributing to alcohol-induced steatosis, ER stress, apoptosis and liver injury in both experimental and human ALD. Our study provides a strong rationale to evaluate AR as a potential therapeutic target and to test AR inhibitors to ameliorate alcohol-induced liver injury. https://www.selleckchem.com/products/Cediranib.html This article is protected by copyright. All rights reserved.PURPOSE Water equivalent diameter (WED) is a robust patient-size descriptor. Localizer-based WED estimation is less sensitive to truncation errors resulting from limited field of view, and produces WED estimates at different locations within one localizer radiograph, prior to the initiation of axial scans. This method is considered difficult to implement by the clinical community due to the necessary calibration between localizer pixel values and attenuation, and the unknown stability of calibration results across scanners and over time. We investigated the stability of calibration results across 25 CT scanners from 3 medical centers, and their stability over 3~29 months for 14 of those scanners. METHODS Localizer and axial images of ACR and body CTDI phantoms were acquired, using routine clinical techniques (120kV and lateral localizers) on each of the 25 CT scanners 8 GE scanners (CT750HD, VCT, and Revolution), 8 Siemens scanners (Definition AS, Force, Flash, and Edge), 5 Canon scanners (Aquilion-One, Aquilion-Prime80, and Aquilion-64), and 4 Philips scanners (iCT 256, iQon, and Ingenuity).
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  • The overall morbidity was 10 % including 5 surgical complications and 5 permanent neurological deficits. Neuropsychological assessments in 60 patients showed considerable preoperative impairment, losses in different domains in 25-45 % and gains in about 25 % of the patients. Postoperative HRQOL data was available in 75 patients, revealing significant increase of HRQOL in all domains. Complete seizure freedom was the strongest predictor for postoperative HRQOL (p less then 0.001). Conclusion Surgery for drug resistant temporal lobe epilepsy is a feasible option for elderly patients as seizure control rates are comparable to the younger population. The acceptable rate of permanent neurological deficits and relevant improvements in quality of life, despite considerable postoperative cognitive impairment, justify surgical resection in properly selected elderly patients.Purpose Children with epilepsy (CWE) are at risk of vitamin D deficiency. Single nucleotide polymorphisms (SNPs) affecting the vitamin D pathway are potentially important risk factors for serum 25-hydroxyvitamin D [25(OH)D] concentration. The aims of our study were to evaluate the association of vitamin d-related SNPs to serum 25(OH)D concentrations in Malaysian CWE. Methods Cross-sectional study of Malaysian ambulant CWE on antiseizure medication for >1 year. Sixteen SNPs in 8 genes (GC, VDR, CYP2R1, CYP24A1, CYP27B1, CYP27A1, CYP3A4, NADSYN1/DHCR7) were genotyped. Linear and logistic regression models and co-variates adjusted analyses were used. SNPs with significant associations were further analysed in a group of ethnically-matched healthy Malaysian children. Results 239 CWE were recruited (52.7% Malay, 24.3% Chinese and 23.0% Indian) with mean serum 25(OH)D of 58.8 nmol/L (SD 25.7). Prevalence of vitamin D deficiency (≤37.5 nmol/L) was 23.0%. Minor allele of GC-rs4588-A was associated with lower serum 25(OH)D in the meta-analysis of both CWE (β -8.11, P = 0.002) and Malaysian healthy children (β -5.08, P less then 0.001), while VDR-rs7975232-A was significantly associated with reduced odds of vitamin D deficiency in Malay subgroup of CWE (OR 0.16; 95% CI 0.06-0.49; P = 0.001) and this association was not found in the healthy children group. Conclusions Our results suggest that GC-rs4588 is associated with lower serum 25(OH)D concentration in both Malaysian CWE and healthy children, while VDR-rs7975232A is associated with lower risk of vitamin D deficiency in Malaysian CWE of Malay ethnicity. Our findings may assist in the genetic risk stratification of low vitamin D status among CWE.Ventrifissura is a group of poorly studied heterotrophic biflagellates in the phylum Cercozoa. Despite a phylogenetic placement with only weak support and a lack of ultrastructural data, Ventrifissura was assigned to Thecofilosea. In the presented study, we established cultures of two novel species of Ventrifissura (V. oblonga n. sp. and V. velata n. sp.) isolated from coastal marine environments in Japan, and performed light and electron microscopy observations and molecular phylogenetic analysis. Transmission electron microscopy revealed that V. oblonga shares several ultrastructural characteristics with thecofilosean flagellates, including permanently condensed chromosomes, a extracellular theca, and slender extrusomes. Molecular phylogenetic analysis could not resolve the phylogenetic position, but the possibility that Ventrifissura clusters into Ventrifilosa was supported by approximately unbiased tests. Based on both morphological and phylogenetic findings, we concluded that Ventrifissura is a basal lineage of Thecofilosea.A novel horseradish peroxidase (HRP) enzyme inhibition biosensor based on indium tin oxide (ITO) nanoparticles, hexaammineruthenium (III) chloride (RUT), and chitosan (CH) modified glassy carbon electrode (GCE) was developed. The biosensor fabrication process was investigated using scanning electron microscopy, energy-dispersive X-ray spectroscopy, cyclic voltammetry, and electrochemical impedance spectroscopy. The amounts of ITO nanoparticles and RUT were optimized using a 22 central composite design for the optimization of electrode composition. The detection limits were determined as 8 nM, 3 nM, and 1 nM for Pb2+, Ni2+, and Cd2+, respectively. The inhibition calibration curves of the biosensor were found to be within the range of 0.009-0.301 µM with a sensitivity of 11.97 µA µM-1 cm-2 (0.85 µA µM-1) for Pb2+, 0.011-0.368 µM with a sensitivity of 10.84 µA µM-1 cm-2 (0.77 µA µM-1) for Ni2+, and 0.008-0.372 µM with a sensitivity of 10.99 µA µM-1 cm-2 (0.78 µA µM-1) for Cd2+. The type of HRP inhibition by Pb2+, Ni2+ and Cd2+ was investigated by the Dixon and Cornish-Bowden plots. The effects of possible interfering species on the biosensor response were examined. The analysis of Pb2+, Ni2+, and Cd2+ in tap water was demonstrated using the HRP/ITO-RUT-CH/GCE with satisfactory experimental results. https://www.selleckchem.com/products/azd-1208.html The proposed method agreed with the atomic absorption spectrometry results.Background Serum biomarkers may inform and improve care in traumatic brain injury (TBI). We aimed to correlate serum biomarkers with clinical severity, care path and imaging abnormalities in TBI, and explore their incremental value over clinical characteristics in predicting computed tomographic (CT) abnormalities. Methods We analyzed six serum biomarkers (S100B, NSE, GFAP, UCH-L1, NFL and t-tau) obtained less then 24 h post-injury from 2867 patients with any severity of TBI in the Collaborative European NeuroTrauma Effectiveness Research (CENTER-TBI) Core Study, a prospective, multicenter, cohort study. Univariable and multivariable logistic regression analyses were performed. Discrimination was assessed by the area under the receiver operating characteristic curve (AUC) with 95% confidence intervals. Findings All biomarkers scaled with clinical severity and care path (ER only, ward admission, or ICU), and with presence of CT abnormalities. GFAP achieved the highest discrimination for predicting CT abnormalities (AUC 0•89 [95%CI 0•87-0•90]), with a 99% likelihood of better discriminating CT-positive patients than clinical characteristics used in contemporary decision rules. In patients with mild TBI, GFAP also showed incremental diagnostic value discrimination increased from 0•84 [95%CI 0•83-0•86] to 0•89 [95%CI 0•87-0•90] when GFAP was included. Results were consistent across strata, and injury severity. Combinations of biomarkers did not improve discrimination compared to GFAP alone. Interpretation Currently available biomarkers reflect injury severity, and serum GFAP, measured within 24 h after injury, outperforms clinical characteristics in predicting CT abnormalities. Our results support the further development of serum GFAP assays towards implementation in clinical practice, for which robust clinical assay platforms are required. Funding CENTER-TBI study was supported by the European Union 7th Framework program (EC grant 602150).
    The overall morbidity was 10 % including 5 surgical complications and 5 permanent neurological deficits. Neuropsychological assessments in 60 patients showed considerable preoperative impairment, losses in different domains in 25-45 % and gains in about 25 % of the patients. Postoperative HRQOL data was available in 75 patients, revealing significant increase of HRQOL in all domains. Complete seizure freedom was the strongest predictor for postoperative HRQOL (p less then 0.001). Conclusion Surgery for drug resistant temporal lobe epilepsy is a feasible option for elderly patients as seizure control rates are comparable to the younger population. The acceptable rate of permanent neurological deficits and relevant improvements in quality of life, despite considerable postoperative cognitive impairment, justify surgical resection in properly selected elderly patients.Purpose Children with epilepsy (CWE) are at risk of vitamin D deficiency. Single nucleotide polymorphisms (SNPs) affecting the vitamin D pathway are potentially important risk factors for serum 25-hydroxyvitamin D [25(OH)D] concentration. The aims of our study were to evaluate the association of vitamin d-related SNPs to serum 25(OH)D concentrations in Malaysian CWE. Methods Cross-sectional study of Malaysian ambulant CWE on antiseizure medication for >1 year. Sixteen SNPs in 8 genes (GC, VDR, CYP2R1, CYP24A1, CYP27B1, CYP27A1, CYP3A4, NADSYN1/DHCR7) were genotyped. Linear and logistic regression models and co-variates adjusted analyses were used. SNPs with significant associations were further analysed in a group of ethnically-matched healthy Malaysian children. Results 239 CWE were recruited (52.7% Malay, 24.3% Chinese and 23.0% Indian) with mean serum 25(OH)D of 58.8 nmol/L (SD 25.7). Prevalence of vitamin D deficiency (≤37.5 nmol/L) was 23.0%. Minor allele of GC-rs4588-A was associated with lower serum 25(OH)D in the meta-analysis of both CWE (β -8.11, P = 0.002) and Malaysian healthy children (β -5.08, P less then 0.001), while VDR-rs7975232-A was significantly associated with reduced odds of vitamin D deficiency in Malay subgroup of CWE (OR 0.16; 95% CI 0.06-0.49; P = 0.001) and this association was not found in the healthy children group. Conclusions Our results suggest that GC-rs4588 is associated with lower serum 25(OH)D concentration in both Malaysian CWE and healthy children, while VDR-rs7975232A is associated with lower risk of vitamin D deficiency in Malaysian CWE of Malay ethnicity. Our findings may assist in the genetic risk stratification of low vitamin D status among CWE.Ventrifissura is a group of poorly studied heterotrophic biflagellates in the phylum Cercozoa. Despite a phylogenetic placement with only weak support and a lack of ultrastructural data, Ventrifissura was assigned to Thecofilosea. In the presented study, we established cultures of two novel species of Ventrifissura (V. oblonga n. sp. and V. velata n. sp.) isolated from coastal marine environments in Japan, and performed light and electron microscopy observations and molecular phylogenetic analysis. Transmission electron microscopy revealed that V. oblonga shares several ultrastructural characteristics with thecofilosean flagellates, including permanently condensed chromosomes, a extracellular theca, and slender extrusomes. Molecular phylogenetic analysis could not resolve the phylogenetic position, but the possibility that Ventrifissura clusters into Ventrifilosa was supported by approximately unbiased tests. Based on both morphological and phylogenetic findings, we concluded that Ventrifissura is a basal lineage of Thecofilosea.A novel horseradish peroxidase (HRP) enzyme inhibition biosensor based on indium tin oxide (ITO) nanoparticles, hexaammineruthenium (III) chloride (RUT), and chitosan (CH) modified glassy carbon electrode (GCE) was developed. The biosensor fabrication process was investigated using scanning electron microscopy, energy-dispersive X-ray spectroscopy, cyclic voltammetry, and electrochemical impedance spectroscopy. The amounts of ITO nanoparticles and RUT were optimized using a 22 central composite design for the optimization of electrode composition. The detection limits were determined as 8 nM, 3 nM, and 1 nM for Pb2+, Ni2+, and Cd2+, respectively. The inhibition calibration curves of the biosensor were found to be within the range of 0.009-0.301 µM with a sensitivity of 11.97 µA µM-1 cm-2 (0.85 µA µM-1) for Pb2+, 0.011-0.368 µM with a sensitivity of 10.84 µA µM-1 cm-2 (0.77 µA µM-1) for Ni2+, and 0.008-0.372 µM with a sensitivity of 10.99 µA µM-1 cm-2 (0.78 µA µM-1) for Cd2+. The type of HRP inhibition by Pb2+, Ni2+ and Cd2+ was investigated by the Dixon and Cornish-Bowden plots. The effects of possible interfering species on the biosensor response were examined. The analysis of Pb2+, Ni2+, and Cd2+ in tap water was demonstrated using the HRP/ITO-RUT-CH/GCE with satisfactory experimental results. https://www.selleckchem.com/products/azd-1208.html The proposed method agreed with the atomic absorption spectrometry results.Background Serum biomarkers may inform and improve care in traumatic brain injury (TBI). We aimed to correlate serum biomarkers with clinical severity, care path and imaging abnormalities in TBI, and explore their incremental value over clinical characteristics in predicting computed tomographic (CT) abnormalities. Methods We analyzed six serum biomarkers (S100B, NSE, GFAP, UCH-L1, NFL and t-tau) obtained less then 24 h post-injury from 2867 patients with any severity of TBI in the Collaborative European NeuroTrauma Effectiveness Research (CENTER-TBI) Core Study, a prospective, multicenter, cohort study. Univariable and multivariable logistic regression analyses were performed. Discrimination was assessed by the area under the receiver operating characteristic curve (AUC) with 95% confidence intervals. Findings All biomarkers scaled with clinical severity and care path (ER only, ward admission, or ICU), and with presence of CT abnormalities. GFAP achieved the highest discrimination for predicting CT abnormalities (AUC 0•89 [95%CI 0•87-0•90]), with a 99% likelihood of better discriminating CT-positive patients than clinical characteristics used in contemporary decision rules. In patients with mild TBI, GFAP also showed incremental diagnostic value discrimination increased from 0•84 [95%CI 0•83-0•86] to 0•89 [95%CI 0•87-0•90] when GFAP was included. Results were consistent across strata, and injury severity. Combinations of biomarkers did not improve discrimination compared to GFAP alone. Interpretation Currently available biomarkers reflect injury severity, and serum GFAP, measured within 24 h after injury, outperforms clinical characteristics in predicting CT abnormalities. Our results support the further development of serum GFAP assays towards implementation in clinical practice, for which robust clinical assay platforms are required. Funding CENTER-TBI study was supported by the European Union 7th Framework program (EC grant 602150).
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  • BACKGROUND Hospital readmission (HR) after surgery is considered a quality metric. METHODS Data on 2371 first-time adult kidney transplant (KT) recipients were collected to analyze the "early" (≤30 days) and "late" (31-365 days) HR patterns after KT at a single center over a 12-year time span (2002-2013). RESULTS 30-day, 90-day, and 1-year HR were 31%, 41%, and 53%, respectively. Risk factors for HR included age >50, female sex, black race, BMI >30, transplant LOS >5 days, and pre-transplant time on dialysis >765 days. Indications for early (n = 749) and late (n = 508) HR were similar. Early HR (OR 3.80, P = .007) and black race (OR 2.38, P = .009) were associated with higher odds of 1-year graft failure while frequency (1-2, 3-4, 5+) of HR (ORs 4.68, 8.36, 9.44, P  5 days increased both odds of 1-year graft failure (OR 3.51, P = .001) and mortality (OR 2.05, P = .006). One-year graft and recipient survival were 96.7% and 94.8%, respectively. CONCLUSIONS Hospital readmission was associated with reduced graft and patient survival; however, despite a relatively high and consistent HR rate after KT, overall 1-year graft and patient survival was high. © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.BACKGROUND Skin diseases are among the most common occupational diseases, but detailed analyses on their epidemiology, diagnoses, and causes are relatively scarce. OBJECTIVES To analyze data on skin disease in the Finnish Register of Occupational Diseases (FROD) for (1) different diagnoses and (2) main causes of allergic contact dermatitis (ACD). METHODS We retrieved data on recognized cases with occupational skin disease (OSD) in the FROD from a 12-year-period 2005-2016 and used national official labor force data of the year 2012. RESULTS We analyzed a total of 5265 cases, of which 42% had irritant contact dermatitis (ICD), 35% ACD, 11% contact urticaria/protein contact dermatitis (CU/PCD), and 9% skin infections. The incidence rate of OSD in the total labor force was 18.8 cases/100 000 person years. Skin infections concerned mainly scabies in health care personnel. Twenty-nine per cent of the ACD cases were caused by plastics/resins-related allergens, mainly epoxy chemicals. Other important causes for ACD were rubber, preservatives, metals, acrylates, and hairdressing chemicals. Cases of occupational ACD due to isothiazolinones reached a peak in 2014. CONCLUSION Our analysis confirms that epoxy products are gaining importance as causes of OSD and the isothiazolinone contact allergy epidemic has started to wane. © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.INTRODUCTION Transfusion protocols are not well-studied for pediatric patients with acute liver failure (ALF). This study evaluates the utility of an international normalized ratio (INR)-based transfusion threshold for these patients. METHODS Forty-four ALF pediatric patients from 2009 to 2018 were reviewed and divided into two groups (a) a threshold group including patients between 2009 and 2015 who were transfused for an INR above 3.0, per institutional policy (n = 30), and (b) a post-threshold group including patients after 2015 through 2018 who were transfused based on clinical judgment (n = 14). Preoperative INRs, preoperative transfusions, intraoperative transfusions, early reoperation, renal function, graft function and deaths were compared. RESULTS Liver failure severity was similar between threshold and post-threshold groups. Threshold patients had a lower average INR prior to transplantation, 2.8 (range 1.8-3.8) vs 4.4 (range 2.1-9.0), respectively (P = .01). Twenty-six threshold patients (87%) received preoperative FFP compared with seven post-threshold patients (50%, P = .0088). Two threshold patients (7%) received preoperative cryoprecipitate compared with five post-threshold patients (36%, P = .014). The incidence of pre-transplant bleeding, operative transfusions, and 1-year patient and graft survival did not differ significantly. CONCLUSION Clinical judgment vs an INR-based threshold for transfusions did not increase perioperative complications in children with ALF. https://www.selleckchem.com/products/shin1-rz-2994.html © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.PURPOSE This study, conducted at a public university in Turkey, sought to determine the effects of yoga-based physical activity on perceived stress, anxiety, and quality of life in young adults. DESIGN AND METHODS This study was planned as a semiexperimental nonrandomized study with a control group. FINDINGS Yoga-based physical activity decreased the perceived stress and state anxiety levels, but had no effect on trait anxiety levels and quality of life. PRACTICAL IMPLICATIONS It is recommended that yoga-based treatment can be included in nursing interventions for reducing stress and anxiety levels in young adults. © 2020 Wiley Periodicals, Inc.Long noncoding RNA colon cancer-associated transcript 2 (CCAT2) has been recently found to function as an oncogene in hepatocellular carcinoma (HCC). However, the mechanisms of CCAT2 in HCC development remain to be further explored. In the present study, we found that CCAT2 was abnormally upregulated in HCC cells and tissue specimens, exhibiting an inverse correlation with microRNA (miR)-145 expression. Mechanistic investigation showed that CCAT2 selectively blocked miR-145 processing, leading to decreased mature miR-145 presence. Both the in vitro and in vivo effects of CCAT2 knockdown on the proliferation and metastasis of HCC cells were reversed by miR-145 inhibitor, indicating that miR-145 modulation accounts for CCAT2-meditated HCC progression. Furthermore, miR-145 mimic dramatically suppressed HCC cells' proliferation and metastasis, revealing a tumor suppressor role of miR-145 in HCC. Mechanistically, MDM2 was predicted to be a potential target of miR-145. The luciferase and western blot assay demonstrated that miR-145 mimic largely inhibited MDM2 3'-untranslated region luciferase activity and MDM2 expression, followed by the upregulation of p53/p21 expression. Finally, the coexpression of MDM2 in miR-145 mimic-transfected HCC cells was able to largely compromise the inhibitory effects of miR-145 mimic on HCC cells' proliferation and metastasis in vitro and tumor formation in a xenograft model, confirming MDM2 is the critical mediator of miR-145 in HCC. In summary, our findings indicated that CCAT2 selectively blocks the miR-145 maturation process and plays an oncogene in HCC. Furthermore, a novel CCAT2/miR-145/MDM2 axis was revealed in HCC development and might provide a new target in the molecular treatment of HCC. © 2020 Wiley Periodicals, Inc.
    BACKGROUND Hospital readmission (HR) after surgery is considered a quality metric. METHODS Data on 2371 first-time adult kidney transplant (KT) recipients were collected to analyze the "early" (≤30 days) and "late" (31-365 days) HR patterns after KT at a single center over a 12-year time span (2002-2013). RESULTS 30-day, 90-day, and 1-year HR were 31%, 41%, and 53%, respectively. Risk factors for HR included age >50, female sex, black race, BMI >30, transplant LOS >5 days, and pre-transplant time on dialysis >765 days. Indications for early (n = 749) and late (n = 508) HR were similar. Early HR (OR 3.80, P = .007) and black race (OR 2.38, P = .009) were associated with higher odds of 1-year graft failure while frequency (1-2, 3-4, 5+) of HR (ORs 4.68, 8.36, 9.44, P  5 days increased both odds of 1-year graft failure (OR 3.51, P = .001) and mortality (OR 2.05, P = .006). One-year graft and recipient survival were 96.7% and 94.8%, respectively. CONCLUSIONS Hospital readmission was associated with reduced graft and patient survival; however, despite a relatively high and consistent HR rate after KT, overall 1-year graft and patient survival was high. © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.BACKGROUND Skin diseases are among the most common occupational diseases, but detailed analyses on their epidemiology, diagnoses, and causes are relatively scarce. OBJECTIVES To analyze data on skin disease in the Finnish Register of Occupational Diseases (FROD) for (1) different diagnoses and (2) main causes of allergic contact dermatitis (ACD). METHODS We retrieved data on recognized cases with occupational skin disease (OSD) in the FROD from a 12-year-period 2005-2016 and used national official labor force data of the year 2012. RESULTS We analyzed a total of 5265 cases, of which 42% had irritant contact dermatitis (ICD), 35% ACD, 11% contact urticaria/protein contact dermatitis (CU/PCD), and 9% skin infections. The incidence rate of OSD in the total labor force was 18.8 cases/100 000 person years. Skin infections concerned mainly scabies in health care personnel. Twenty-nine per cent of the ACD cases were caused by plastics/resins-related allergens, mainly epoxy chemicals. Other important causes for ACD were rubber, preservatives, metals, acrylates, and hairdressing chemicals. Cases of occupational ACD due to isothiazolinones reached a peak in 2014. CONCLUSION Our analysis confirms that epoxy products are gaining importance as causes of OSD and the isothiazolinone contact allergy epidemic has started to wane. © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.INTRODUCTION Transfusion protocols are not well-studied for pediatric patients with acute liver failure (ALF). This study evaluates the utility of an international normalized ratio (INR)-based transfusion threshold for these patients. METHODS Forty-four ALF pediatric patients from 2009 to 2018 were reviewed and divided into two groups (a) a threshold group including patients between 2009 and 2015 who were transfused for an INR above 3.0, per institutional policy (n = 30), and (b) a post-threshold group including patients after 2015 through 2018 who were transfused based on clinical judgment (n = 14). Preoperative INRs, preoperative transfusions, intraoperative transfusions, early reoperation, renal function, graft function and deaths were compared. RESULTS Liver failure severity was similar between threshold and post-threshold groups. Threshold patients had a lower average INR prior to transplantation, 2.8 (range 1.8-3.8) vs 4.4 (range 2.1-9.0), respectively (P = .01). Twenty-six threshold patients (87%) received preoperative FFP compared with seven post-threshold patients (50%, P = .0088). Two threshold patients (7%) received preoperative cryoprecipitate compared with five post-threshold patients (36%, P = .014). The incidence of pre-transplant bleeding, operative transfusions, and 1-year patient and graft survival did not differ significantly. CONCLUSION Clinical judgment vs an INR-based threshold for transfusions did not increase perioperative complications in children with ALF. https://www.selleckchem.com/products/shin1-rz-2994.html © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.PURPOSE This study, conducted at a public university in Turkey, sought to determine the effects of yoga-based physical activity on perceived stress, anxiety, and quality of life in young adults. DESIGN AND METHODS This study was planned as a semiexperimental nonrandomized study with a control group. FINDINGS Yoga-based physical activity decreased the perceived stress and state anxiety levels, but had no effect on trait anxiety levels and quality of life. PRACTICAL IMPLICATIONS It is recommended that yoga-based treatment can be included in nursing interventions for reducing stress and anxiety levels in young adults. © 2020 Wiley Periodicals, Inc.Long noncoding RNA colon cancer-associated transcript 2 (CCAT2) has been recently found to function as an oncogene in hepatocellular carcinoma (HCC). However, the mechanisms of CCAT2 in HCC development remain to be further explored. In the present study, we found that CCAT2 was abnormally upregulated in HCC cells and tissue specimens, exhibiting an inverse correlation with microRNA (miR)-145 expression. Mechanistic investigation showed that CCAT2 selectively blocked miR-145 processing, leading to decreased mature miR-145 presence. Both the in vitro and in vivo effects of CCAT2 knockdown on the proliferation and metastasis of HCC cells were reversed by miR-145 inhibitor, indicating that miR-145 modulation accounts for CCAT2-meditated HCC progression. Furthermore, miR-145 mimic dramatically suppressed HCC cells' proliferation and metastasis, revealing a tumor suppressor role of miR-145 in HCC. Mechanistically, MDM2 was predicted to be a potential target of miR-145. The luciferase and western blot assay demonstrated that miR-145 mimic largely inhibited MDM2 3'-untranslated region luciferase activity and MDM2 expression, followed by the upregulation of p53/p21 expression. Finally, the coexpression of MDM2 in miR-145 mimic-transfected HCC cells was able to largely compromise the inhibitory effects of miR-145 mimic on HCC cells' proliferation and metastasis in vitro and tumor formation in a xenograft model, confirming MDM2 is the critical mediator of miR-145 in HCC. In summary, our findings indicated that CCAT2 selectively blocks the miR-145 maturation process and plays an oncogene in HCC. Furthermore, a novel CCAT2/miR-145/MDM2 axis was revealed in HCC development and might provide a new target in the molecular treatment of HCC. © 2020 Wiley Periodicals, Inc.
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  • © 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.Conjugated materials can, in many cases, absorb visible light because of their delocalized π electron system. Such materials have been widely used as a photoactive layers in organic photovoltaic devices and as photosensitizers in dye-sensitized solar cells. Additionally, these materials have been reported for applications in solar fuel production, working as photocatalysts for the hydrogen evolution reaction (HER). The synthesis of three flexible vinyl groups-containing chromophores is reported. The catalytic activity towards hydrogen evolution of these chromophores has been investigated and compared to their non-vinyl-containing analogues. The catalytic effect was confirmed using two different approaches electrochemical, using the chromophores to modify a working electrode, and photocatalytic, using the chromophores combined with platinum nanoparticles. A relationship between the degree of conjugation and the catalytic activity of the chromophores has been observed with the electrochemical method, while a relationship between the UV absorption in the solid state and the photocatalytic effect with platinum nanoparticles was observed. © 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.The chemical recycling of end-of-life polymers can add some value to a future circular economy. In this regard, the hydrogenative degradation of end-of-life PLA was investigated to produce 1,2-propanediol as product, which is a useful building block in polymer chemistry. In more detail, the commercially available Ru-MACHO-BH complex was applied as catalyst to degrade end-of-life PLA efficiently to 1,2-propanediol under mild conditions. After investigations of the reaction conditions a set of end-of-life PLA goods were subjected to degradation. © 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.Rotaxane building blocks bearing 3,5-bis(trifluoromethyl) benzenesulfonate (BTBS) stoppers have been efficiently prepared from a pillar[5]arene derivative, 3,5-bis(trifluoromethyl) benzenesulfonyl chloride (BTBSCl) and different diols, namely 1,10-decanediol and 1,12-dodecanediol. The BTBS moieties of these compounds are good leaving groups and stopper exchange reactions could be achieved by treatment with different nucleophiles thus affording rotaxanes with ester, thioether or ether stoppers. © 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.DNA was used as supramolecular scaffold to order chromophores and control their optical properties. Ethynylpyrene as energy donor was attached to 2'-desoxy-2-aminoadenosine that binds selectively to thymidines (T) in the template. Ethynylperylene as acceptor was attached to 2'-desoxyuridine that is complementary to 2'-desoxyadenosine (A). https://www.selleckchem.com/products/ykl5-124.html This donor-acceptor pair was assembled along single-stranded DNA templates of different A-T sequences to investigate the sequence control of the energy transfer between the chromophores. The fluorescence intensities increase in the mixed assemblies along the DNA templates from A10T10 over (AATT)5 to (AT)10, although these templates provide equal numbers of potential binding sites for the two different nucleoside chromophore conjugates and exhibit similar absorbances. This shows that the sequence selective assembly of the two building blocks along DNA templates is programmable and alters the fluorescence readout. Such sequence-controlled supramolecular chemistry represents the key element for future functional π-systems in materials for light harvesting of solar energy. © 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.Invited for this month's cover are Iwona and Jean-François Nierengarten from the University of Strasbourg. The cover picture shows the structure of a [2]rotaxane building block bearing 3,5-bis(trifluoromethyl) benzenesulfonate (BTBS) stoppers. The BTBS moieties of this compound are good leaving groups allowing to perform stopper exchange by treatment with different nucleophiles to afford the corresponding rotaxanes with ester, ether or thioether stoppers. Read the full text of their Full Paper at https//doi.org/10.1002/open.202000035. © 2020 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim.The study aims to determine the timing of application for high efficacy of Metarhizium anisopliae as a biocontrol agent. A field experiment was undertaken with M. anisopliae applied to the soil at five intervals during the peanut crop lifecycle, at seed germination (day 0) through to pod filling period [75 days after sowing (DAS)], and assessed the change of M. anisopliae density by sampling rhizospheric soil, subsequently at regular intervals and testing counts (CFU/g dry soil) through to harvest. The crop was sown into soil with an established white grub population, with larval density determined at harvest when the trial was concluded. Applications at 0, 15 and 30 days in the crop growth cycle, saw M. anisopliae mean propagule counts drop significantly after 15 days before increasing over the following 15-45 days. We observed an elevated mean increase in counts 30-45 days after application at the early flowering stage (30 DAS). Irrespective of application timing, in general, M. anisopliae densities declined to less than the initial 10% in the late stages of peanut development. At harvest, larval densities in all M. anisopliae treatments were significantly less compared to the control, with the highest mortality (72%) in M. anisopliae treatment applied at early flowering (30 DAS). Relationship analysis showed that white grub density was significantly related to peanut yield. A regression of yield on number of damaged pods also supported that treatment at the early flowering caused the highest impact in terms of reducing damage to pods and improving yield. These results suggest that applying M. anisopliae at the early flowering stage optimizes survival of M. anisopliae in the soil profile, meaning greater probability of larvae contacting the pathogen, leading to greater mortality. © King Abdulaziz City for Science and Technology 2020.This study explored the effect of methyl-indole on pancreatic cancer cell viability and investigated the mechanism involved. The viability of pancreatic cells showed a significant suppression on treatment with methyl-indole in dose-based manner. Treatment with 5 µM methyl-indole suppressed Capan-1 cell viability to 23%. The viability of Aspc-1 cells was reduced to 20% and those of MIApaCa-2 cells to 18% by 5 µM methyl-indole. The apoptotic proportion of Capan-1 cells was 67%, while as those of Aspc-1 and MIApaCa-2 cells increased to 72 and 77%, respectively, on treatment with 5 µM methyl-indole. The level of P13K, p-Tyr, p-Crkl and p-Akt was inhibited in the cells by methyl-indole. Moreover, methyl-indole also suppressed zinc-finger protein, X-linked mRNA and protein expression in tested cells. In summary, methyl-indole exhibits anti-proliferative effect on pancreatic cancer cells and induces apoptosis. It targeted ZFX expression and down-regulated P13K/AKT pathway in pancreatic cancer cells. Therefore, methyl-indole acts as therapeutic agent for pancreatic cancer and may be studied further.
    © 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.Conjugated materials can, in many cases, absorb visible light because of their delocalized π electron system. Such materials have been widely used as a photoactive layers in organic photovoltaic devices and as photosensitizers in dye-sensitized solar cells. Additionally, these materials have been reported for applications in solar fuel production, working as photocatalysts for the hydrogen evolution reaction (HER). The synthesis of three flexible vinyl groups-containing chromophores is reported. The catalytic activity towards hydrogen evolution of these chromophores has been investigated and compared to their non-vinyl-containing analogues. The catalytic effect was confirmed using two different approaches electrochemical, using the chromophores to modify a working electrode, and photocatalytic, using the chromophores combined with platinum nanoparticles. A relationship between the degree of conjugation and the catalytic activity of the chromophores has been observed with the electrochemical method, while a relationship between the UV absorption in the solid state and the photocatalytic effect with platinum nanoparticles was observed. © 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.The chemical recycling of end-of-life polymers can add some value to a future circular economy. In this regard, the hydrogenative degradation of end-of-life PLA was investigated to produce 1,2-propanediol as product, which is a useful building block in polymer chemistry. In more detail, the commercially available Ru-MACHO-BH complex was applied as catalyst to degrade end-of-life PLA efficiently to 1,2-propanediol under mild conditions. After investigations of the reaction conditions a set of end-of-life PLA goods were subjected to degradation. © 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.Rotaxane building blocks bearing 3,5-bis(trifluoromethyl) benzenesulfonate (BTBS) stoppers have been efficiently prepared from a pillar[5]arene derivative, 3,5-bis(trifluoromethyl) benzenesulfonyl chloride (BTBSCl) and different diols, namely 1,10-decanediol and 1,12-dodecanediol. The BTBS moieties of these compounds are good leaving groups and stopper exchange reactions could be achieved by treatment with different nucleophiles thus affording rotaxanes with ester, thioether or ether stoppers. © 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.DNA was used as supramolecular scaffold to order chromophores and control their optical properties. Ethynylpyrene as energy donor was attached to 2'-desoxy-2-aminoadenosine that binds selectively to thymidines (T) in the template. Ethynylperylene as acceptor was attached to 2'-desoxyuridine that is complementary to 2'-desoxyadenosine (A). https://www.selleckchem.com/products/ykl5-124.html This donor-acceptor pair was assembled along single-stranded DNA templates of different A-T sequences to investigate the sequence control of the energy transfer between the chromophores. The fluorescence intensities increase in the mixed assemblies along the DNA templates from A10T10 over (AATT)5 to (AT)10, although these templates provide equal numbers of potential binding sites for the two different nucleoside chromophore conjugates and exhibit similar absorbances. This shows that the sequence selective assembly of the two building blocks along DNA templates is programmable and alters the fluorescence readout. Such sequence-controlled supramolecular chemistry represents the key element for future functional π-systems in materials for light harvesting of solar energy. © 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.Invited for this month's cover are Iwona and Jean-François Nierengarten from the University of Strasbourg. The cover picture shows the structure of a [2]rotaxane building block bearing 3,5-bis(trifluoromethyl) benzenesulfonate (BTBS) stoppers. The BTBS moieties of this compound are good leaving groups allowing to perform stopper exchange by treatment with different nucleophiles to afford the corresponding rotaxanes with ester, ether or thioether stoppers. Read the full text of their Full Paper at https//doi.org/10.1002/open.202000035. © 2020 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim.The study aims to determine the timing of application for high efficacy of Metarhizium anisopliae as a biocontrol agent. A field experiment was undertaken with M. anisopliae applied to the soil at five intervals during the peanut crop lifecycle, at seed germination (day 0) through to pod filling period [75 days after sowing (DAS)], and assessed the change of M. anisopliae density by sampling rhizospheric soil, subsequently at regular intervals and testing counts (CFU/g dry soil) through to harvest. The crop was sown into soil with an established white grub population, with larval density determined at harvest when the trial was concluded. Applications at 0, 15 and 30 days in the crop growth cycle, saw M. anisopliae mean propagule counts drop significantly after 15 days before increasing over the following 15-45 days. We observed an elevated mean increase in counts 30-45 days after application at the early flowering stage (30 DAS). Irrespective of application timing, in general, M. anisopliae densities declined to less than the initial 10% in the late stages of peanut development. At harvest, larval densities in all M. anisopliae treatments were significantly less compared to the control, with the highest mortality (72%) in M. anisopliae treatment applied at early flowering (30 DAS). Relationship analysis showed that white grub density was significantly related to peanut yield. A regression of yield on number of damaged pods also supported that treatment at the early flowering caused the highest impact in terms of reducing damage to pods and improving yield. These results suggest that applying M. anisopliae at the early flowering stage optimizes survival of M. anisopliae in the soil profile, meaning greater probability of larvae contacting the pathogen, leading to greater mortality. © King Abdulaziz City for Science and Technology 2020.This study explored the effect of methyl-indole on pancreatic cancer cell viability and investigated the mechanism involved. The viability of pancreatic cells showed a significant suppression on treatment with methyl-indole in dose-based manner. Treatment with 5 µM methyl-indole suppressed Capan-1 cell viability to 23%. The viability of Aspc-1 cells was reduced to 20% and those of MIApaCa-2 cells to 18% by 5 µM methyl-indole. The apoptotic proportion of Capan-1 cells was 67%, while as those of Aspc-1 and MIApaCa-2 cells increased to 72 and 77%, respectively, on treatment with 5 µM methyl-indole. The level of P13K, p-Tyr, p-Crkl and p-Akt was inhibited in the cells by methyl-indole. Moreover, methyl-indole also suppressed zinc-finger protein, X-linked mRNA and protein expression in tested cells. In summary, methyl-indole exhibits anti-proliferative effect on pancreatic cancer cells and induces apoptosis. It targeted ZFX expression and down-regulated P13K/AKT pathway in pancreatic cancer cells. Therefore, methyl-indole acts as therapeutic agent for pancreatic cancer and may be studied further.
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