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  • Blockade of VEGFR-1, but not VEGFR-2 with neutralizing Abs completely abolished the suppressive effect of PlGF. Furthermore, we found that treatment with PlGF up-regulated IL-10 production in CD4+ and CD8+ T cells, promoted CD8+ T cells apoptosis and enhanced the expression of inhibitory receptors (PD-1 and TIM-3) on activated T cells. Our in vitro findings suggest the involvement of PlGF/VEGFR-1 signaling in the modulation of T cell responses in a-CD3-stimulated PBMCs. ©2020 Society for Leukocyte Biology.BACKGROUND The fluorescence sensing method has been increasingly applied in food quality control because it is fast and sensitive. However, its application in quality evaluation is challenging. Using Citri Reticulatae Pericarpium (CRP, dried mandarin orange peel) as an example, we developed a simple and low-cost fluorescence sensing strategy based on nanoparticles combined with spectral splicing and chemometrics for quality evaluation. This method can recognize the Citrus reticulata 'Chachi' (CRC) from other CRP cultivars and further identify the storage year. RESULTS Nanogold particles and cadmium telluride quantum dots were selected as nanosensors and mixed with aqueous extracts of CRP separately to produce fluorescence quenching spectra. Then, a simple spectral splicing procedure was applied to obtain spliced spectra comprising different combinations of the self-fluorescence and fluorescence-quenching spectra of CRP samples. With the aid of partial least square discriminant analysis (PLSDA), the new strategy achieved recognition rates of 100% in distinguishing the CRC samples from other CRP samples, as well as recognition rates of 100% for training set and 98.04% for predicted set in the discrimination of the storage year of CRC. The recognition mechanism is dominated by interactions between the nanoparticles and the fluorescent components in the CRP samples, but other components also have concurrent effects. CONCLUSION This novel fluorescence sensing strategy not only provides a new tool for the quality evaluation of CRC but also has good prospects for the authentication and traceability of other foods and herbs. Crucially, the developed method is more convenient, simpler, and more effective. This article is protected by copyright. All rights reserved. https://www.selleckchem.com/products/Imatinib-Mesylate.html This article is protected by copyright. All rights reserved.BACKGROUND AND PURPOSE This study aims to investigate whether radiomic quantitative image features (IFs) from perfusion dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) retain sufficient strength to predict O6-methylguanine-DNA methyltransferase promoter methylation (MGMT_pm) in newly diagnosed glioblastoma (GB) patients. METHODS We retrospectively reviewed the perfusion DSC-MRI of 59 patients with GB. Patients were classified into three groups (1) unmethylated if MGMT_pm ≤ 9% (UM); (2) intermediate-methylated if MGMT_pm ranged between 10% and 29% (IM); (3) methylated if MGMT_pm ≥ 30% (M). A total of 92 quantitative IFs were obtained from relative cerebral blood volume and relative cerebral blood flow maps. The Mann-Whitney U-test was applied to assess whether there were statistical differences in IFs between patient groups. Those IFs showing significant difference between two patient groups were termed relevant IFs (rIFs). rIFs were uploaded to a machine learning model to predict the MGMT_pm. RESULTS No rIFs were found between UM and IM groups. Fourteen rIFs were found among UM-M, IM-M, and (UM + IM)-M groups. We built a multilayer perceptron deep learning model that classified patients as belonging to UM + IM and M group. The model performed well with 75% sensitivity, 85% specificity, and an area under the receiver-operating curve of .84. CONCLUSION rIFs from perfusion DSC-MRI are potential biomarkers in GBs with a ≥30% MGMT_pm. Otherwise, unmethylated and intermediate-methylated GBs lack of rIFs. Five of 14 rIFs show sufficient strength to build an accurate prediction model of MGMT_pm. © 2020 by the American Society of Neuroimaging.OBJECTIVE Community reentry post-incarceration is fraught with challenges. The investigators examined the influence of highly personalized goals (possible selves) on psychological well-being, drug use, and hazardous drinking in recently incarcerated young men returning to the community. DESIGN AND SAMPLE In this cross-sectional study, 52 young men released from jail or prison within the past 12 months were recruited from community-based organizations and reentry events. MEASUREMENTS Participants completed open-ended possible selves measure and psychological well-being and substance use questionnaires. RESULTS Possible selves accounted for 19%-31% of the variance in sense of purpose, environmental mastery, and personal growth. Having a feared delinquent possible self was associated with lower sense of purpose. Having many feared possible selves was associated with lower environmental mastery. Having an expected possible self related to interpersonal relationships was associated with higher personal growth and environmental mastery. Men having a feared delinquent possible self or an expected possible self related to material/lifestyle were more likely to use marijuana than men who did not. CONCLUSION The content and number of possible selves may be an important focus for assessment by public health nurses in correctional and community settings serving young men post-incarceration. Longitudinal studies with larger samples are needed. © 2020 Wiley Periodicals, Inc.Chemokines play critical roles in numerous physiologic and pathologic processes through their action on seven-transmembrane (TM) receptors. The N-terminal domain of chemokines, which is a key determinant of signaling via its binding within a pocket formed by receptors' TM helices, can be the target of proteolytic processing. An illustrative case of this regulatory mechanism is the natural processing of CXCL12 that generates chemokine variants lacking the first two N-terminal residues. Whereas such truncated variants behave as antagonists of CXCR4, the canonical G protein-coupled receptor of CXCL12, they are agonists of the atypical chemokine receptor 3 (ACKR3/CXCR7), suggesting the implication of different structural determinants in the complexes formed between CXCL12 and its two receptors. Recent analyses have suggested that the CXCL12 N-terminus first engages the TM helices of ACKR3 followed by the receptor N-terminus wrapping around the chemokine core. Here we investigated the first stage of ACKR3-CXCL12 interactions by comparing the activity of substituted or N-terminally truncated variants of CXCL12 toward CXCR4 and ACKR3.
    Blockade of VEGFR-1, but not VEGFR-2 with neutralizing Abs completely abolished the suppressive effect of PlGF. Furthermore, we found that treatment with PlGF up-regulated IL-10 production in CD4+ and CD8+ T cells, promoted CD8+ T cells apoptosis and enhanced the expression of inhibitory receptors (PD-1 and TIM-3) on activated T cells. Our in vitro findings suggest the involvement of PlGF/VEGFR-1 signaling in the modulation of T cell responses in a-CD3-stimulated PBMCs. ©2020 Society for Leukocyte Biology.BACKGROUND The fluorescence sensing method has been increasingly applied in food quality control because it is fast and sensitive. However, its application in quality evaluation is challenging. Using Citri Reticulatae Pericarpium (CRP, dried mandarin orange peel) as an example, we developed a simple and low-cost fluorescence sensing strategy based on nanoparticles combined with spectral splicing and chemometrics for quality evaluation. This method can recognize the Citrus reticulata 'Chachi' (CRC) from other CRP cultivars and further identify the storage year. RESULTS Nanogold particles and cadmium telluride quantum dots were selected as nanosensors and mixed with aqueous extracts of CRP separately to produce fluorescence quenching spectra. Then, a simple spectral splicing procedure was applied to obtain spliced spectra comprising different combinations of the self-fluorescence and fluorescence-quenching spectra of CRP samples. With the aid of partial least square discriminant analysis (PLSDA), the new strategy achieved recognition rates of 100% in distinguishing the CRC samples from other CRP samples, as well as recognition rates of 100% for training set and 98.04% for predicted set in the discrimination of the storage year of CRC. The recognition mechanism is dominated by interactions between the nanoparticles and the fluorescent components in the CRP samples, but other components also have concurrent effects. CONCLUSION This novel fluorescence sensing strategy not only provides a new tool for the quality evaluation of CRC but also has good prospects for the authentication and traceability of other foods and herbs. Crucially, the developed method is more convenient, simpler, and more effective. This article is protected by copyright. All rights reserved. https://www.selleckchem.com/products/Imatinib-Mesylate.html This article is protected by copyright. All rights reserved.BACKGROUND AND PURPOSE This study aims to investigate whether radiomic quantitative image features (IFs) from perfusion dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) retain sufficient strength to predict O6-methylguanine-DNA methyltransferase promoter methylation (MGMT_pm) in newly diagnosed glioblastoma (GB) patients. METHODS We retrospectively reviewed the perfusion DSC-MRI of 59 patients with GB. Patients were classified into three groups (1) unmethylated if MGMT_pm ≤ 9% (UM); (2) intermediate-methylated if MGMT_pm ranged between 10% and 29% (IM); (3) methylated if MGMT_pm ≥ 30% (M). A total of 92 quantitative IFs were obtained from relative cerebral blood volume and relative cerebral blood flow maps. The Mann-Whitney U-test was applied to assess whether there were statistical differences in IFs between patient groups. Those IFs showing significant difference between two patient groups were termed relevant IFs (rIFs). rIFs were uploaded to a machine learning model to predict the MGMT_pm. RESULTS No rIFs were found between UM and IM groups. Fourteen rIFs were found among UM-M, IM-M, and (UM + IM)-M groups. We built a multilayer perceptron deep learning model that classified patients as belonging to UM + IM and M group. The model performed well with 75% sensitivity, 85% specificity, and an area under the receiver-operating curve of .84. CONCLUSION rIFs from perfusion DSC-MRI are potential biomarkers in GBs with a ≥30% MGMT_pm. Otherwise, unmethylated and intermediate-methylated GBs lack of rIFs. Five of 14 rIFs show sufficient strength to build an accurate prediction model of MGMT_pm. © 2020 by the American Society of Neuroimaging.OBJECTIVE Community reentry post-incarceration is fraught with challenges. The investigators examined the influence of highly personalized goals (possible selves) on psychological well-being, drug use, and hazardous drinking in recently incarcerated young men returning to the community. DESIGN AND SAMPLE In this cross-sectional study, 52 young men released from jail or prison within the past 12 months were recruited from community-based organizations and reentry events. MEASUREMENTS Participants completed open-ended possible selves measure and psychological well-being and substance use questionnaires. RESULTS Possible selves accounted for 19%-31% of the variance in sense of purpose, environmental mastery, and personal growth. Having a feared delinquent possible self was associated with lower sense of purpose. Having many feared possible selves was associated with lower environmental mastery. Having an expected possible self related to interpersonal relationships was associated with higher personal growth and environmental mastery. Men having a feared delinquent possible self or an expected possible self related to material/lifestyle were more likely to use marijuana than men who did not. CONCLUSION The content and number of possible selves may be an important focus for assessment by public health nurses in correctional and community settings serving young men post-incarceration. Longitudinal studies with larger samples are needed. © 2020 Wiley Periodicals, Inc.Chemokines play critical roles in numerous physiologic and pathologic processes through their action on seven-transmembrane (TM) receptors. The N-terminal domain of chemokines, which is a key determinant of signaling via its binding within a pocket formed by receptors' TM helices, can be the target of proteolytic processing. An illustrative case of this regulatory mechanism is the natural processing of CXCL12 that generates chemokine variants lacking the first two N-terminal residues. Whereas such truncated variants behave as antagonists of CXCR4, the canonical G protein-coupled receptor of CXCL12, they are agonists of the atypical chemokine receptor 3 (ACKR3/CXCR7), suggesting the implication of different structural determinants in the complexes formed between CXCL12 and its two receptors. Recent analyses have suggested that the CXCL12 N-terminus first engages the TM helices of ACKR3 followed by the receptor N-terminus wrapping around the chemokine core. Here we investigated the first stage of ACKR3-CXCL12 interactions by comparing the activity of substituted or N-terminally truncated variants of CXCL12 toward CXCR4 and ACKR3.
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  • Leclercia sp. W6 and W17, which belong to the Enterobacteriaceae, were isolated from a stomach sample from a 78-year-old female gastric cancer patient, and genomic sequencing and analysis were performed. The genome of Leclercia sp. W6 consists of one chromosome with a size of 4,945,486 bp, while that of Leclercia sp. W17 contains one chromosome and two plasmids with a total size of 5,125,645 bp. Average nucleotide identity (ANI) calculations indicated that strains W6 and W17 exhibited similarities less then 91.0% to other strains within the Enterobacteriaceae, except for six Leclercia strains. Phylogenomic analysis based on core-genome showed that strains W6 and W17 belong to the genus Leclercia, and phylogenetic analysis based on ANI values revealed that strains W6 and W17 formed an independent clade from those six Leclercia strains. Furthermore, comparative genomic analysis revealed that strains W6 and W17 had 5086 orthologous clusters (OCs) in their pan-genomes, and 59 exclusive OCs which were absent in their closest relatives. Genomic annotations revealed that the genomes of strains W6 and W17 encoded genes related to multidrug resistance clusters, multiple antibiotic resistance loci, and multidrug efflux pumps and had an identical urease gene cluster and a dissimilatory nitrate reduction pathway. Bioinformatic analyses indicated that strains W6 and W17 represented a novel species within the genus Leclercia. Genomic annotations revealed that these strains encoded genes related to multidrug resistance, nitrate reduction, and urease activity, which contribute to gastric malignant transformation. This will broaden our knowledge of the genetic mechanisms of the Enterobacteriaceae and help improve the clinical conditions of gastric cancer patients.T regulatory (Treg) cells play a critical role in the maintenance of self-tolerance, as well as in inhibition of inflammation and exaggerated immune response against exogenous antigens. They develop in the thymus (tTreg cells) but also may be generated at the peripheral tissues, including tumor microenvironment (pTreg cells), or induced in vitro in the presence of transforming growth factor (TGF)-β (iTreg cells). Since tTreg cells constitute a minor fraction of peripheral blood lymphocytes in physiological conditions, an alternative way to obtain high number of functional Treg cells for therapeutic purposes is their generation in vitro from conventional T cells. In our studies, we compared effectiveness of several pharmacological agents with suggested immunomodulatory effects on Treg development (rapamycin, prednisolone, inosine pranobex, glatiramer acetate, sodium butyrate, and atorvastatin) to optimize Treg-inducing protocols. All but one (atorvastatin) immunomodulators augmented induction of polyclonal Treg cells in cultures. They were effective both in increasing the number of CD4+CD25highFoxp3high cells and Foxp3 expression. Rapamycin and prednisolone were found the most effective. Both drugs prolonged also phenotypic stability of Treg cells and induced fully active Treg cells in a functional assay. In the assay, prednisolone appeared superior versus rapamycin. The results, on the one hand, may be helpful in planning optimal protocols for generation of Treg cells for clinical application and, on the other hand, shed some light on mechanisms of the immunomodulatory activity of some tested agents observed in vivo.Purpose The Spanish Society of Medical Oncology (SEOM) has carried out a study to analyse the conditions of access to oncology drugs in clinical practice in Spain. For the first time, the access of predictive biomarkers has also been analyzed. Methods A questionnaire was sent to 146 hospitals in Spain to collect information on the process of approval of 11 oncology drugs of an unquestionable clinical benefit and five predictive biomarkers of mandatory determination for specific treatments. Results Results highlight the still existing differences in the access of oncology drugs, as well as the newly identified differences in the access to predictive biomarkers between Autonomous Communities (AACC) in Spain, as well as between different hospitals within the same Autonomous Community. Conclusions The SEOM considers it necessary to reduce the differences identified, increase homogeneity, and improve conditions of access to oncology drugs and biomarkers, and makes proposals to address these issues.Purpose Tryptophan metabolites have immunomodulatory functions, suggesting possible roles in cancer immunity. https://www.selleckchem.com/products/vx803-m4344.html Methods Plasma tryptophan metabolites were measured using liquid chromatography/mass spectrometry before immune checkpoint inhibitors (ICIs) in patients with non-small cell lung cancer (NSCLC). Results The 19 patients with NSCLC had significantly lower levels of tryptophan (p = 0.002) and xanthurenic acid (p = 0.032), and a significantly higher level of 3-hydroxyanthranilic acid (3-HAA) (p = 0.028) compared with the 10 healthy volunteers. The patients achieving objective responses had significantly lower levels of 3-HAA than those who did not (p = 0.045). Receiver operating characteristic analyses determined that the cutoff value of 3-HAA for objective response was 35.4 pmol/mL (sensitivity 87.5% and specificity 83.3%). The patients with 3-HAA less then 35.4 pmol/mL had significantly longer median progression-free survival (7.0 months) than those without (1.6 months, p = 0.022). Conclusions Tryptophan metabolites may have a potential for predicting the efficacy of ICIs. Registration number University Hospital Medical Information Network Clinical Trial Registry 000026140.Purpose Guidance and quality control in orthopedic surgery increasingly rely on intra-operative fluoroscopy using a mobile C-arm. The accurate acquisition of standardized and anatomy-specific projections is essential in this process. The corresponding iterative positioning of the C-arm is error prone and involves repeated manual acquisitions or even continuous fluoroscopy. To reduce time and radiation exposure for patients and clinical staff and to avoid errors in fracture reduction or implant placement, we aim at guiding-and in the long-run automating-this procedure. Methods In contrast to the state of the art, we tackle this inherently ill-posed problem without requiring patient-individual prior information like preoperative computed tomography (CT) scans, without the need of registration and without requiring additional technical equipment besides the projection images themselves. We propose learning the necessary anatomical hints for efficient C-arm positioning from in silico simulations, leveraging masses of 3D CTs.
    Leclercia sp. W6 and W17, which belong to the Enterobacteriaceae, were isolated from a stomach sample from a 78-year-old female gastric cancer patient, and genomic sequencing and analysis were performed. The genome of Leclercia sp. W6 consists of one chromosome with a size of 4,945,486 bp, while that of Leclercia sp. W17 contains one chromosome and two plasmids with a total size of 5,125,645 bp. Average nucleotide identity (ANI) calculations indicated that strains W6 and W17 exhibited similarities less then 91.0% to other strains within the Enterobacteriaceae, except for six Leclercia strains. Phylogenomic analysis based on core-genome showed that strains W6 and W17 belong to the genus Leclercia, and phylogenetic analysis based on ANI values revealed that strains W6 and W17 formed an independent clade from those six Leclercia strains. Furthermore, comparative genomic analysis revealed that strains W6 and W17 had 5086 orthologous clusters (OCs) in their pan-genomes, and 59 exclusive OCs which were absent in their closest relatives. Genomic annotations revealed that the genomes of strains W6 and W17 encoded genes related to multidrug resistance clusters, multiple antibiotic resistance loci, and multidrug efflux pumps and had an identical urease gene cluster and a dissimilatory nitrate reduction pathway. Bioinformatic analyses indicated that strains W6 and W17 represented a novel species within the genus Leclercia. Genomic annotations revealed that these strains encoded genes related to multidrug resistance, nitrate reduction, and urease activity, which contribute to gastric malignant transformation. This will broaden our knowledge of the genetic mechanisms of the Enterobacteriaceae and help improve the clinical conditions of gastric cancer patients.T regulatory (Treg) cells play a critical role in the maintenance of self-tolerance, as well as in inhibition of inflammation and exaggerated immune response against exogenous antigens. They develop in the thymus (tTreg cells) but also may be generated at the peripheral tissues, including tumor microenvironment (pTreg cells), or induced in vitro in the presence of transforming growth factor (TGF)-β (iTreg cells). Since tTreg cells constitute a minor fraction of peripheral blood lymphocytes in physiological conditions, an alternative way to obtain high number of functional Treg cells for therapeutic purposes is their generation in vitro from conventional T cells. In our studies, we compared effectiveness of several pharmacological agents with suggested immunomodulatory effects on Treg development (rapamycin, prednisolone, inosine pranobex, glatiramer acetate, sodium butyrate, and atorvastatin) to optimize Treg-inducing protocols. All but one (atorvastatin) immunomodulators augmented induction of polyclonal Treg cells in cultures. They were effective both in increasing the number of CD4+CD25highFoxp3high cells and Foxp3 expression. Rapamycin and prednisolone were found the most effective. Both drugs prolonged also phenotypic stability of Treg cells and induced fully active Treg cells in a functional assay. In the assay, prednisolone appeared superior versus rapamycin. The results, on the one hand, may be helpful in planning optimal protocols for generation of Treg cells for clinical application and, on the other hand, shed some light on mechanisms of the immunomodulatory activity of some tested agents observed in vivo.Purpose The Spanish Society of Medical Oncology (SEOM) has carried out a study to analyse the conditions of access to oncology drugs in clinical practice in Spain. For the first time, the access of predictive biomarkers has also been analyzed. Methods A questionnaire was sent to 146 hospitals in Spain to collect information on the process of approval of 11 oncology drugs of an unquestionable clinical benefit and five predictive biomarkers of mandatory determination for specific treatments. Results Results highlight the still existing differences in the access of oncology drugs, as well as the newly identified differences in the access to predictive biomarkers between Autonomous Communities (AACC) in Spain, as well as between different hospitals within the same Autonomous Community. Conclusions The SEOM considers it necessary to reduce the differences identified, increase homogeneity, and improve conditions of access to oncology drugs and biomarkers, and makes proposals to address these issues.Purpose Tryptophan metabolites have immunomodulatory functions, suggesting possible roles in cancer immunity. https://www.selleckchem.com/products/vx803-m4344.html Methods Plasma tryptophan metabolites were measured using liquid chromatography/mass spectrometry before immune checkpoint inhibitors (ICIs) in patients with non-small cell lung cancer (NSCLC). Results The 19 patients with NSCLC had significantly lower levels of tryptophan (p = 0.002) and xanthurenic acid (p = 0.032), and a significantly higher level of 3-hydroxyanthranilic acid (3-HAA) (p = 0.028) compared with the 10 healthy volunteers. The patients achieving objective responses had significantly lower levels of 3-HAA than those who did not (p = 0.045). Receiver operating characteristic analyses determined that the cutoff value of 3-HAA for objective response was 35.4 pmol/mL (sensitivity 87.5% and specificity 83.3%). The patients with 3-HAA less then 35.4 pmol/mL had significantly longer median progression-free survival (7.0 months) than those without (1.6 months, p = 0.022). Conclusions Tryptophan metabolites may have a potential for predicting the efficacy of ICIs. Registration number University Hospital Medical Information Network Clinical Trial Registry 000026140.Purpose Guidance and quality control in orthopedic surgery increasingly rely on intra-operative fluoroscopy using a mobile C-arm. The accurate acquisition of standardized and anatomy-specific projections is essential in this process. The corresponding iterative positioning of the C-arm is error prone and involves repeated manual acquisitions or even continuous fluoroscopy. To reduce time and radiation exposure for patients and clinical staff and to avoid errors in fracture reduction or implant placement, we aim at guiding-and in the long-run automating-this procedure. Methods In contrast to the state of the art, we tackle this inherently ill-posed problem without requiring patient-individual prior information like preoperative computed tomography (CT) scans, without the need of registration and without requiring additional technical equipment besides the projection images themselves. We propose learning the necessary anatomical hints for efficient C-arm positioning from in silico simulations, leveraging masses of 3D CTs.
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  • To evaluate the accuracy of 3D models of the aortic-root generated from non-contrast cardiac magnetic resonance (CMR). Data were retrospectively collected from 30 consecutive patients who underwent surgical aortic valve replacement and had available records of both intra-operative assessment and pre-surgery annulus assessment by cardiovascular computed tomography (CCT) and CMR. The 3D models were independently segmented, modelled and printed by two blinded "manufacturers". The measurements on the models were carried out by two cardiac surgeons with Hegar dilator. Data were analyzed with non-parametric tests. There was no significant intra- or inter-observer variability (p ≥ 0.13). The agreement between the diameter of the 3D model derived from CMR images and either the anatomical reference of the intraoperative measurement (p = 0.10, r = 0.97) or the radiological reference of the 3D model generated from CCT (p = 0.71, r = 0.92) was very good. The process of segmentation plus the post-processing was about 17 ± 2 min for a model created by CMR, significantly higher than a model created from CCT (7 ± 2 min; p less then 0.001). The printing time for a single model did not differ between the two modalities (p = 0.61) and was less than 60 min. The cost for a single model was approximately 0.5 €. 3D models generated from non-contrast CMR performed well when compared to the anatomical reference standard and are comparable to the pair CCT derived models.Down syndrome (DS) is one of the most common causes of intellectual disability and new approaches allowing its rapid and effective prenatal detection are being explored. In this study, we investigated the diagnostic potential of plasma microRNAs (miRNAs). This study builds upon our previous study in DS placentas, where seven miRNAs were found to be significantly up-regulated. A total of 70 first-trimester plasma samples from pregnant women were included in the present study (35 samples with DS fetuses; 35 with euploid fetuses). Genome-wide miRNA profiling was performed in the pilot study using Affymetrix GeneChip™ miRNA 4.1 Array Strips (18 samples). Selected miRNAs were then analysed in the validation study using quantitative reverse transcription PCR (RT-qPCR; 52 samples). Based on the current pilot study results (12 miRNAs), our previous research on chorionic villi samples (7 miRNAs) and the literature (4 miRNAs), a group of 23 miRNAs was selected for the validation study. Although the results of the pilot study were promising, the validation study using the more sensitive RT-qPCR technique and a larger group of samples revealed no significant differences in miRNA profiles between the compared groups. Our results suggest that testing of the first-trimester plasma miRNAs is probably not suitable for non-invasive prenatal testing (NIPT). Different results could be theoretically achieved at later gestational ages; however, such a result probably would have limited use in clinical practice.Essential thrombocythemia (ET) is a classical myeloproliferative neoplasm that is susceptible to hypercoagulable state due to impaired hemostatic system, so that thrombotic complications are the leading cause of mortality in ET patients. The content used in this article has been obtained by the PubMed database and Google Scholar search engine from English-language articles (2000-2019) using the following keywords "Essential thrombocythemia," "Thrombosis," "Risk factors" and "Hemostasis. In this neoplasm, the count and activity of cells such as platelets, leukocytes, endothelial cells, as well as erythrocytes are increased, which can increase the risk of thrombosis through rising intercellular interactions, expression of surface markers, and stimulation of platelet aggregation. https://www.selleckchem.com/products/PD-0332991.html In addition to these factors, genetic polymorphisms in hematopoietic stem cells (HSCs), including mutations in JAK2, CALR, MPL, or genetic abnormalities in other genes associated with the hemostatic system may be associated with increased risk of thrombotic events. Moreover, disruption of coagulant factors can pave the way for thrombogeneration. Therefore, the identification of markers related to cell activation, genetic abnormalities, or alternation in the coagulant system can be used together as diagnostic and prognostic markers for the occurrence of thrombosis among ET patients. Thus, because thrombotic complications are the main factors of mortality in ET patients, a hemostatic viewpoint and risk assessment of cellular, genetic, and coagulation factors can have prognostic value and contribute to the choice of effective treatment and prevention of thrombosis.Paroxonase 1 (PON 1) enzymatic activity and Q192R PON polymorphism has been implicated with greater cardiovascular risk in general population. Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized with increased inflammatory markers leading to increased cardiovascular morbidity. The aim of the work was to study association between PON1 enzymatic activity & gene polymorphism with carotid plaques in RA patients. This case-control study was carried out at Zagazig University Hospitals on 99 subjects divided randomly into two groups; 48 RA patients and 51 controls. RA patients fulfilled the revised 2010 EULAR/ACR classification criteria of RA. All patients were subjected to history taking, clinical evaluation, laboratory investigations & plain X-rays. Carotid intima-media thickness (CIMT) and PON1 enzyme assay & genotyping were done for both groups. PON1 enzyme levels were significantly higher in patients than controls. Also, there was a significant negative correlation of PON1 enzyme activity with increased CIMT & plaques. The cut-off value of PON1 enzyme level that had the highest CVD prediction was 4.2 U/ml. Although PON1 genotyping was insignificantly different between patients and controls, patients with QQ genotype had the lowest PON1 activity then patients with QR genotype then RR genotype. In RA patients, decreased serum PON1 enzymatic activity and QQ genotyping of Q192R PON polymorphism was associated with increased CIMT & plaques. Serum PON1 could be a good marker for atherosclerosis prediction in RA patients at cutoff 4.2 U/ml.
    To evaluate the accuracy of 3D models of the aortic-root generated from non-contrast cardiac magnetic resonance (CMR). Data were retrospectively collected from 30 consecutive patients who underwent surgical aortic valve replacement and had available records of both intra-operative assessment and pre-surgery annulus assessment by cardiovascular computed tomography (CCT) and CMR. The 3D models were independently segmented, modelled and printed by two blinded "manufacturers". The measurements on the models were carried out by two cardiac surgeons with Hegar dilator. Data were analyzed with non-parametric tests. There was no significant intra- or inter-observer variability (p ≥ 0.13). The agreement between the diameter of the 3D model derived from CMR images and either the anatomical reference of the intraoperative measurement (p = 0.10, r = 0.97) or the radiological reference of the 3D model generated from CCT (p = 0.71, r = 0.92) was very good. The process of segmentation plus the post-processing was about 17 ± 2 min for a model created by CMR, significantly higher than a model created from CCT (7 ± 2 min; p less then 0.001). The printing time for a single model did not differ between the two modalities (p = 0.61) and was less than 60 min. The cost for a single model was approximately 0.5 €. 3D models generated from non-contrast CMR performed well when compared to the anatomical reference standard and are comparable to the pair CCT derived models.Down syndrome (DS) is one of the most common causes of intellectual disability and new approaches allowing its rapid and effective prenatal detection are being explored. In this study, we investigated the diagnostic potential of plasma microRNAs (miRNAs). This study builds upon our previous study in DS placentas, where seven miRNAs were found to be significantly up-regulated. A total of 70 first-trimester plasma samples from pregnant women were included in the present study (35 samples with DS fetuses; 35 with euploid fetuses). Genome-wide miRNA profiling was performed in the pilot study using Affymetrix GeneChip™ miRNA 4.1 Array Strips (18 samples). Selected miRNAs were then analysed in the validation study using quantitative reverse transcription PCR (RT-qPCR; 52 samples). Based on the current pilot study results (12 miRNAs), our previous research on chorionic villi samples (7 miRNAs) and the literature (4 miRNAs), a group of 23 miRNAs was selected for the validation study. Although the results of the pilot study were promising, the validation study using the more sensitive RT-qPCR technique and a larger group of samples revealed no significant differences in miRNA profiles between the compared groups. Our results suggest that testing of the first-trimester plasma miRNAs is probably not suitable for non-invasive prenatal testing (NIPT). Different results could be theoretically achieved at later gestational ages; however, such a result probably would have limited use in clinical practice.Essential thrombocythemia (ET) is a classical myeloproliferative neoplasm that is susceptible to hypercoagulable state due to impaired hemostatic system, so that thrombotic complications are the leading cause of mortality in ET patients. The content used in this article has been obtained by the PubMed database and Google Scholar search engine from English-language articles (2000-2019) using the following keywords "Essential thrombocythemia," "Thrombosis," "Risk factors" and "Hemostasis. In this neoplasm, the count and activity of cells such as platelets, leukocytes, endothelial cells, as well as erythrocytes are increased, which can increase the risk of thrombosis through rising intercellular interactions, expression of surface markers, and stimulation of platelet aggregation. https://www.selleckchem.com/products/PD-0332991.html In addition to these factors, genetic polymorphisms in hematopoietic stem cells (HSCs), including mutations in JAK2, CALR, MPL, or genetic abnormalities in other genes associated with the hemostatic system may be associated with increased risk of thrombotic events. Moreover, disruption of coagulant factors can pave the way for thrombogeneration. Therefore, the identification of markers related to cell activation, genetic abnormalities, or alternation in the coagulant system can be used together as diagnostic and prognostic markers for the occurrence of thrombosis among ET patients. Thus, because thrombotic complications are the main factors of mortality in ET patients, a hemostatic viewpoint and risk assessment of cellular, genetic, and coagulation factors can have prognostic value and contribute to the choice of effective treatment and prevention of thrombosis.Paroxonase 1 (PON 1) enzymatic activity and Q192R PON polymorphism has been implicated with greater cardiovascular risk in general population. Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized with increased inflammatory markers leading to increased cardiovascular morbidity. The aim of the work was to study association between PON1 enzymatic activity & gene polymorphism with carotid plaques in RA patients. This case-control study was carried out at Zagazig University Hospitals on 99 subjects divided randomly into two groups; 48 RA patients and 51 controls. RA patients fulfilled the revised 2010 EULAR/ACR classification criteria of RA. All patients were subjected to history taking, clinical evaluation, laboratory investigations & plain X-rays. Carotid intima-media thickness (CIMT) and PON1 enzyme assay & genotyping were done for both groups. PON1 enzyme levels were significantly higher in patients than controls. Also, there was a significant negative correlation of PON1 enzyme activity with increased CIMT & plaques. The cut-off value of PON1 enzyme level that had the highest CVD prediction was 4.2 U/ml. Although PON1 genotyping was insignificantly different between patients and controls, patients with QQ genotype had the lowest PON1 activity then patients with QR genotype then RR genotype. In RA patients, decreased serum PON1 enzymatic activity and QQ genotyping of Q192R PON polymorphism was associated with increased CIMT & plaques. Serum PON1 could be a good marker for atherosclerosis prediction in RA patients at cutoff 4.2 U/ml.
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  • A general paediatrician with research expertise in SDM discusses the individual and system level challenges and rewards of using SDM in her clinical practice. Based on the viewpoints presented, we offer pragmatic recommendations for using SDM in paediatric clinical practice. © 2020 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).Streptococcus mutans is a major etiologic agent of dental caries, which is the most common chronic infectious disease worldwide. S. mutans is particularly adept at causing caries due to its exceptional capacity to form biofilms and its ability to survive acidic conditions that arrest acid production and growth in many more benign members of the oral microbiota. Two mechanisms utilized by S. mutans to tolerate acid are modulation of the membrane fatty acid content and utilization of the F1 F0 -ATPase to pump protons out of the cytosol. In this study, the role of the spxA2 transcriptional regulator in these two pathways, and overall cell envelope homeostasis, was examined. Loss of spxA2 resulted in an increase in the proportion of saturated fatty acids in the S. mutans membrane and altered transcription of several genes involved in the production of these membrane fatty acids, including fabT and fabM. Furthermore, activity of the F1 F0 -ATPase was increased in the ∆spxA2 strain. Transcription of spxA2 was elevated in the presence of a variety of membrane stressors, and highly dependent on the liaR component of the LiaFSR system, which is known to sense cell envelope stress in many Gram-positive bacteria. Finally, deletion of ∆spxA2 led to altered susceptibility of S. mutans to membrane stressors. Overall, the results of this study indicate that spxA2 serves a crucial role in transmitting the signal of cell wall/membrane damage from the LiaFSR sensor to downstream effectors in the SpxA2 regulon which restore and maintain membrane and cell wall homeostasis. © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.AIMS AND OBJECTIVES To examine the level of self-care behaviours among patients with diabetic foot ulcers and identify factors related to their self-care behaviours. BACKGROUND This study focused on the self-care behaviours of patients diagnosed with diabetic foot ulcers, a complication of diabetes. DESIGN A cross-sectional study design was adopted. METHODS From July-August 2018, 131 outpatients and inpatients with diabetic foot ulcers were given a survey questionnaire regarding self-care behaviours and expected related factors at two Korean hospitals. In this study, self-care behaviours were diabetes management and diabetic foot care. Demographic, disease-related and laboratory characteristics were collected. https://www.selleckchem.com/products/DMXAA(ASA404).html The data were analysed in terms of descriptive statistics, a t test, ANOVA, Pearson's correlation coefficient and stepwise multiple regression. STROBE checklist was used as the guideline for this study. RESULTS Moderate levels of self-care behaviours were found. The stepwise multiple regression analysisommended to promote the self-care behaviours of patients with diabetic foot ulcers. © 2020 John Wiley & Sons Ltd.AIM To assess self-reported clinical competence and the need for further training among newly graduated registered nurses (NGRNs) working in Swedish acute care hospital settings. BACKGROUND NGRNs are expected to take full responsibility for patients' nursing care in an increasingly complex clinical context, and professional nurses' clinical competence is critical in providing high-quality and safe nursing care. DESIGN A cross-sectional design. METHODS Data were collected using the 50-item ProffNurse SAS II. A total of 85 NGRNs who had recently commenced working with direct patient care at three hospitals in central Sweden participated in the study. The response rate was 69%. The STROBE cross-sectional reporting guidelines were used. RESULTS The NGRNs assessed their clinical competence as being highest in areas relating to team collaboration and ethics and lowest in areas relating to professional development and direct clinical practice. The need for further training was greatest in areas such as direct clinical practice and patient safety and lowest in areas such as team collaborating and ethics. CONCLUSION The use of instruments to identify NGRNs' self-assessed clinical competence is of value when designing and evaluating introductory programmes for NGRNs taking on positions in acute care hospital settings. The availability of experienced nurses from whom NGRNs can gain clinical competence and learn from is of importance, both from the perspective of the NGRNs themselves and patient safety. RELEVANCE TO CLINICAL PRACTICE An understanding of NGRNs' clinical competence and their need for further training may assist in both planning and organising nursing programmes and in making clinical policy decisions when designing introduction programmes in acute care settings. © 2020 The Authors. Journal of Clinical Nursing published by John Wiley & Sons Ltd.With the rapid development of nanotechnology, nanomaterials are now being used for cancer treatment. Although studies on the application of silver nanoparticles in cancer treatment are burgeoning, few studies have investigated the toxicology mechanisms of autophagy in cancer cells under exposure to sublethal silver nanoparticles. Here, we clarified the distinct mechanisms of silver nanoparticles for the regulation of autophagy in prostate cancer PC-3 cells under sublethal exposure. Silver nanoparticle treatment caused lysosome injury, including the decline of lysosomal membrane integrity, decrease of lysosomal quantity, and attenuation of lysosomal protease activity, which resulted in blockage of autophagic flux. In addition, sublethal silver nanoparticle exposure activated AMP-activated protein kinase/mammalian target of rapamycin-dependent signaling pathway to modulate autophagy, which resulted from silver nanoparticles-induced cell hypoxia and energy deficiency. Taken together, the results show that silver nanoparticles could regulate autophagy via lysosome injury and cell hypoxia in PC-3 cells under sublethal dose exposure. This study will provide an experimental basis for the cancer therapy of nanomaterials. © 2020 Wiley Periodicals, Inc.
    A general paediatrician with research expertise in SDM discusses the individual and system level challenges and rewards of using SDM in her clinical practice. Based on the viewpoints presented, we offer pragmatic recommendations for using SDM in paediatric clinical practice. © 2020 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).Streptococcus mutans is a major etiologic agent of dental caries, which is the most common chronic infectious disease worldwide. S. mutans is particularly adept at causing caries due to its exceptional capacity to form biofilms and its ability to survive acidic conditions that arrest acid production and growth in many more benign members of the oral microbiota. Two mechanisms utilized by S. mutans to tolerate acid are modulation of the membrane fatty acid content and utilization of the F1 F0 -ATPase to pump protons out of the cytosol. In this study, the role of the spxA2 transcriptional regulator in these two pathways, and overall cell envelope homeostasis, was examined. Loss of spxA2 resulted in an increase in the proportion of saturated fatty acids in the S. mutans membrane and altered transcription of several genes involved in the production of these membrane fatty acids, including fabT and fabM. Furthermore, activity of the F1 F0 -ATPase was increased in the ∆spxA2 strain. Transcription of spxA2 was elevated in the presence of a variety of membrane stressors, and highly dependent on the liaR component of the LiaFSR system, which is known to sense cell envelope stress in many Gram-positive bacteria. Finally, deletion of ∆spxA2 led to altered susceptibility of S. mutans to membrane stressors. Overall, the results of this study indicate that spxA2 serves a crucial role in transmitting the signal of cell wall/membrane damage from the LiaFSR sensor to downstream effectors in the SpxA2 regulon which restore and maintain membrane and cell wall homeostasis. © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.AIMS AND OBJECTIVES To examine the level of self-care behaviours among patients with diabetic foot ulcers and identify factors related to their self-care behaviours. BACKGROUND This study focused on the self-care behaviours of patients diagnosed with diabetic foot ulcers, a complication of diabetes. DESIGN A cross-sectional study design was adopted. METHODS From July-August 2018, 131 outpatients and inpatients with diabetic foot ulcers were given a survey questionnaire regarding self-care behaviours and expected related factors at two Korean hospitals. In this study, self-care behaviours were diabetes management and diabetic foot care. Demographic, disease-related and laboratory characteristics were collected. https://www.selleckchem.com/products/DMXAA(ASA404).html The data were analysed in terms of descriptive statistics, a t test, ANOVA, Pearson's correlation coefficient and stepwise multiple regression. STROBE checklist was used as the guideline for this study. RESULTS Moderate levels of self-care behaviours were found. The stepwise multiple regression analysisommended to promote the self-care behaviours of patients with diabetic foot ulcers. © 2020 John Wiley & Sons Ltd.AIM To assess self-reported clinical competence and the need for further training among newly graduated registered nurses (NGRNs) working in Swedish acute care hospital settings. BACKGROUND NGRNs are expected to take full responsibility for patients' nursing care in an increasingly complex clinical context, and professional nurses' clinical competence is critical in providing high-quality and safe nursing care. DESIGN A cross-sectional design. METHODS Data were collected using the 50-item ProffNurse SAS II. A total of 85 NGRNs who had recently commenced working with direct patient care at three hospitals in central Sweden participated in the study. The response rate was 69%. The STROBE cross-sectional reporting guidelines were used. RESULTS The NGRNs assessed their clinical competence as being highest in areas relating to team collaboration and ethics and lowest in areas relating to professional development and direct clinical practice. The need for further training was greatest in areas such as direct clinical practice and patient safety and lowest in areas such as team collaborating and ethics. CONCLUSION The use of instruments to identify NGRNs' self-assessed clinical competence is of value when designing and evaluating introductory programmes for NGRNs taking on positions in acute care hospital settings. The availability of experienced nurses from whom NGRNs can gain clinical competence and learn from is of importance, both from the perspective of the NGRNs themselves and patient safety. RELEVANCE TO CLINICAL PRACTICE An understanding of NGRNs' clinical competence and their need for further training may assist in both planning and organising nursing programmes and in making clinical policy decisions when designing introduction programmes in acute care settings. © 2020 The Authors. Journal of Clinical Nursing published by John Wiley & Sons Ltd.With the rapid development of nanotechnology, nanomaterials are now being used for cancer treatment. Although studies on the application of silver nanoparticles in cancer treatment are burgeoning, few studies have investigated the toxicology mechanisms of autophagy in cancer cells under exposure to sublethal silver nanoparticles. Here, we clarified the distinct mechanisms of silver nanoparticles for the regulation of autophagy in prostate cancer PC-3 cells under sublethal exposure. Silver nanoparticle treatment caused lysosome injury, including the decline of lysosomal membrane integrity, decrease of lysosomal quantity, and attenuation of lysosomal protease activity, which resulted in blockage of autophagic flux. In addition, sublethal silver nanoparticle exposure activated AMP-activated protein kinase/mammalian target of rapamycin-dependent signaling pathway to modulate autophagy, which resulted from silver nanoparticles-induced cell hypoxia and energy deficiency. Taken together, the results show that silver nanoparticles could regulate autophagy via lysosome injury and cell hypoxia in PC-3 cells under sublethal dose exposure. This study will provide an experimental basis for the cancer therapy of nanomaterials. © 2020 Wiley Periodicals, Inc.
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  • Along with the classical histological clues, evaluation of the clinical findings and less-defined histological features may enhance the diagnostic accuracy. To the best of our knowledge, this study represents the first original study focusing on the clinical and pathological aspects of CSMTs in our country.Anthropogenic metal contamination results in long-term environmental selective pressure with unclear impacts on bacterial communities which comprise key players in ecosystem functioning. Since metal contamination poses serious toxicity and bioaccumulation issues, assessing their impact on environmental microbiomes is important to respond to current environmental and health issues. Despite elevated metal concentrations, the river sedimentary microbiome near the MetalEurop foundry (France) shows unexpected higher diversity compared to upstream control site. In this work, a follow-up of the microbial community assembly during a metal contamination event was performed in microcosms with periodic renewal of the supernatant river water. Sediments of the control site were gradually exposed to a mixture of metals (Cd, Cu, Pb and Zn), in order to reach similar concentrations to MetalEurop sediments. Illumina sequencing of 16S rRNA gene amplicons was performed. Metal resistance genes czcA and pbrA, as well as IncP plasmid content were assessed by quantitative PCR. The outcomes of this study support previous in-situ observations showing that metals act as community assembly managers, increasing diversity. This work revealed progressive adaptation of the sediment microbiome through the selection of different metal-resistance mechanisms and cross-species interactions involving public good providing bacteria co-occurring with the rest of the community. © FEMS 2020.Importance Suicidal ideation is a widespread phenomenon. However, many individuals at risk for suicide do not seek treatment, which might be addressed by providing low-threshold, internet-based self-help interventions. Objective To investigate whether internet-based self-help interventions directly targeting suicidal ideation or behavior are associated with reductions in suicidal ideation. Data Sources A systematic search of PsycINFO, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and the Centre for Research Excellence of Suicide Prevention (CRESP) databases for trials from inception to April 6, 2019, was performed, supplemented by reference searches. Search strings consisted of various search terms related to the concepts of internet, suicide, and randomized clinical trials. Study Selection Two independent researchers reviewed titles, abstracts, and full texts. Randomized clinical trials evaluating the effectiveness of internet-based self-help interventions to reduce suicidal ideation wer reduced suicidal ideation compared with controls following intervention in all 6 trials (standardized mean difference, -0.29; 95% CI, -0.40 to -0.19; P  less then  .001). Heterogeneity was low (I2 = 0%). The effect appeared to be maintained at follow-up in 4 trials (standardized mean difference, -0.18; 95% CI, -0.34 to -0.02; P = .03; I2 = 36%). Studies did not report sufficient data on completed suicides and suicide attempts to assess potential associations. Conclusions and Relevance These results show that iCBT interventions are associated with significant reductions in suicidal ideation compared with control conditions. Considering their high scalability, iCBT interventions have the potential to reduce suicide mortality. Future research should assess the effect of these digital health interventions on suicidal behavior and identify moderators and mediators to advance understanding of the mechanisms of effectiveness of these interventions.Importance Epileptiform electroencephalographic (EEG) patterns are common after resuscitation from cardiac arrest, are associated with patient outcome, and may require treatment. It is unknown whether continuous EEG monitoring is needed to detect these patterns or if brief intermittent monitoring is sufficient. If continuous monitoring is required, the necessary duration of observation is unknown. Objective To quantify the time-dependent sensitivity of continuous EEG for epileptiform event detection, and to compare continuous EEG to several alternative EEG-monitoring strategies for post-cardiac arrest outcome prediction. Design, Setting, and Participants This observational cohort study was conducted in 2 academic medical centers between September 2010 and January 2018. Participants included 759 adults who were comatose after being resuscitated from cardiac arrest and who underwent 24 hours or more of EEG monitoring. Main Outcomes and Measures Epileptiform EEG patterns associated with neurological outcome at hwhen added to multivariable models predicting neurological outcome. Conclusions and Relevance Compared with continuous EEG monitoring, brief intermittent monitoring was insensitive for detection of epileptiform events. Monitoring EEG results significantly improved multimodality prediction of neurological outcome, but continuous monitoring appeared to add little additional information compared with brief intermittent monitoring.Importance Rates of total knee arthroplasty vary widely across the United States. Whether this variation is associated with differences in patient characteristics or physician practice is unknown. https://www.selleckchem.com/products/Fulvestrant.html Objectives To determine regional variations in rates of total knee arthroplasty after accounting for the prevalence of knee arthritis and other potentially associated patient risk factors and to assess the correlation of these variations with measures of access to care and surgical indications. Design, Setting, and Participants This retrospective national cohort study used Medicare data on more than 24 million deidentified beneficiaries annually from 2011 to 2015. Individuals included had fee-for-service coverage, were 65 to 89 years of age, and resided in 1 of 306 health referral regions. Data were analyzed from September 13, 2018, to August 15, 2019. Main Outcomes and Measures Rate of primary total knee arthroplasty indexed to the national rate using observed to expected ratios. The expected numbers of arthroplasty procedures were derived from estimates based on beneficiaries' demographic and clinical characteristics.
    Along with the classical histological clues, evaluation of the clinical findings and less-defined histological features may enhance the diagnostic accuracy. To the best of our knowledge, this study represents the first original study focusing on the clinical and pathological aspects of CSMTs in our country.Anthropogenic metal contamination results in long-term environmental selective pressure with unclear impacts on bacterial communities which comprise key players in ecosystem functioning. Since metal contamination poses serious toxicity and bioaccumulation issues, assessing their impact on environmental microbiomes is important to respond to current environmental and health issues. Despite elevated metal concentrations, the river sedimentary microbiome near the MetalEurop foundry (France) shows unexpected higher diversity compared to upstream control site. In this work, a follow-up of the microbial community assembly during a metal contamination event was performed in microcosms with periodic renewal of the supernatant river water. Sediments of the control site were gradually exposed to a mixture of metals (Cd, Cu, Pb and Zn), in order to reach similar concentrations to MetalEurop sediments. Illumina sequencing of 16S rRNA gene amplicons was performed. Metal resistance genes czcA and pbrA, as well as IncP plasmid content were assessed by quantitative PCR. The outcomes of this study support previous in-situ observations showing that metals act as community assembly managers, increasing diversity. This work revealed progressive adaptation of the sediment microbiome through the selection of different metal-resistance mechanisms and cross-species interactions involving public good providing bacteria co-occurring with the rest of the community. © FEMS 2020.Importance Suicidal ideation is a widespread phenomenon. However, many individuals at risk for suicide do not seek treatment, which might be addressed by providing low-threshold, internet-based self-help interventions. Objective To investigate whether internet-based self-help interventions directly targeting suicidal ideation or behavior are associated with reductions in suicidal ideation. Data Sources A systematic search of PsycINFO, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and the Centre for Research Excellence of Suicide Prevention (CRESP) databases for trials from inception to April 6, 2019, was performed, supplemented by reference searches. Search strings consisted of various search terms related to the concepts of internet, suicide, and randomized clinical trials. Study Selection Two independent researchers reviewed titles, abstracts, and full texts. Randomized clinical trials evaluating the effectiveness of internet-based self-help interventions to reduce suicidal ideation wer reduced suicidal ideation compared with controls following intervention in all 6 trials (standardized mean difference, -0.29; 95% CI, -0.40 to -0.19; P  less then  .001). Heterogeneity was low (I2 = 0%). The effect appeared to be maintained at follow-up in 4 trials (standardized mean difference, -0.18; 95% CI, -0.34 to -0.02; P = .03; I2 = 36%). Studies did not report sufficient data on completed suicides and suicide attempts to assess potential associations. Conclusions and Relevance These results show that iCBT interventions are associated with significant reductions in suicidal ideation compared with control conditions. Considering their high scalability, iCBT interventions have the potential to reduce suicide mortality. Future research should assess the effect of these digital health interventions on suicidal behavior and identify moderators and mediators to advance understanding of the mechanisms of effectiveness of these interventions.Importance Epileptiform electroencephalographic (EEG) patterns are common after resuscitation from cardiac arrest, are associated with patient outcome, and may require treatment. It is unknown whether continuous EEG monitoring is needed to detect these patterns or if brief intermittent monitoring is sufficient. If continuous monitoring is required, the necessary duration of observation is unknown. Objective To quantify the time-dependent sensitivity of continuous EEG for epileptiform event detection, and to compare continuous EEG to several alternative EEG-monitoring strategies for post-cardiac arrest outcome prediction. Design, Setting, and Participants This observational cohort study was conducted in 2 academic medical centers between September 2010 and January 2018. Participants included 759 adults who were comatose after being resuscitated from cardiac arrest and who underwent 24 hours or more of EEG monitoring. Main Outcomes and Measures Epileptiform EEG patterns associated with neurological outcome at hwhen added to multivariable models predicting neurological outcome. Conclusions and Relevance Compared with continuous EEG monitoring, brief intermittent monitoring was insensitive for detection of epileptiform events. Monitoring EEG results significantly improved multimodality prediction of neurological outcome, but continuous monitoring appeared to add little additional information compared with brief intermittent monitoring.Importance Rates of total knee arthroplasty vary widely across the United States. Whether this variation is associated with differences in patient characteristics or physician practice is unknown. https://www.selleckchem.com/products/Fulvestrant.html Objectives To determine regional variations in rates of total knee arthroplasty after accounting for the prevalence of knee arthritis and other potentially associated patient risk factors and to assess the correlation of these variations with measures of access to care and surgical indications. Design, Setting, and Participants This retrospective national cohort study used Medicare data on more than 24 million deidentified beneficiaries annually from 2011 to 2015. Individuals included had fee-for-service coverage, were 65 to 89 years of age, and resided in 1 of 306 health referral regions. Data were analyzed from September 13, 2018, to August 15, 2019. Main Outcomes and Measures Rate of primary total knee arthroplasty indexed to the national rate using observed to expected ratios. The expected numbers of arthroplasty procedures were derived from estimates based on beneficiaries' demographic and clinical characteristics.
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  • 2 m) in average levels of shallow groundwater systems, which may occur in Northern Europe within the coming two decades, can increase mass flows of metals through groundwater by a factor of 2-10. There is a similar risk of increased metal mobilization in regions subject to increased (seasonal or event-scale) amplitude of groundwater levels fluctuations. Neglecting groundwater level dynamics in predictive models can thus lead to considerable and systematic underestimation of metal mobilization and future changes. More generally, our results suggest that the key to quantifying impacts of climate change on metal mobilization is to understand how the contact between groundwater and the highly water-conducting and geochemically heterogeneous topsoil layers will change in the future. Polychlorinated dibenzo-p-dioxins and dibenzofurans are a group of chemically-related pollutants categorically known as dioxins. Some of their chlorinated congeners are among the most hazardous pollutants that persist in the environment. This persistence is due in part to the limited number of bacteria capable of metabolizing these compounds, but also to their limited bioavailability in soil. We used Sphingomonas wittichii strain RW1 (RW1), one of the few strains able to grow on dioxin, to characterize its ability to respond to and degrade clay-bound dioxin. We found that RW1 grew on and completely degraded dibenzo-p-dioxin (DD) intercalated into the smectite clay saponite (SAP). To characterize the effects of DD sorption on RW1 gene expression, we compared transcriptomes of RW1 grown with either free crystalline DD or DD intercalated clay, i.e. sandwiched between the clay interlayers (DDSAP). Free crystalline DD appeared to cause greater expression of toxicity and stress related functions. Genes coding for heat shock proteins, chaperones, as well as genes involved in DNA repair, and efflux were up-regulated during growth on crystalline dioxin compared to growth on intercalated dioxin. In contrast, growth on intercalated dioxin up-regulated genes that might be important in recognition and uptake mechanisms, as well as surface interaction/attachment/biofilm formation such as extracellular solute-binding protein and LuxR. These differences in gene expression may reflect the underlying adaptive mechanisms by which RW1 cells sense and deploy pathways to access dioxin intercalated into clay. These data show that intercalated DD remains bioavailable to the degrading bacterium with implications for bioremediation alternatives. Dissolved organic nitrogen (DON) with a mixture of various organic nitrogen (N) is recognized as an emerging groundwater contaminant. Investigating the behavior and mechanism of DON sorption onto clay minerals, which are key components of vadose zone media, is crucial to evaluating its leaching potential. Considering the interactions among multiple DON compounds (DONs) may influence their sorption behaviors, the sorption of three typical DONs (amino acid, protein and urea) to clay minerals in single-, binary- and ternary-solute systems were explored, respectively. In addition, a combination of multiple methods, including physiochemical characterization, Fourier Transform Infrared Spectroscopy (FTIR), X-ray diffraction (XRD) and pH variation analysis, were used to provide insight into the governing mechanisms. Results indicated that the sorption kinetics and isotherms of single systems were well-fitted by pseudo-second-order and Freundlich isotherm models, respectively. The mechanisms involved in the sorption DONs in the vadose zone and their leachability into groundwater. In most investigations of adsorption process, the effects of adsorbate properties on adsorption capacity were often not obtain enough attention, compared with the properties of adsorbent. Apart from the polarity, and the boiling point of adsorbate, the molecular space conformation is also play an important role in its adsorption behavior on porous materials. In this work, two series of orientation-designed activated carbon were used to study the microscopic adsorption behavior of amphiphilic propylene glycol methyl ether (PM) gas. The spatial conformation of the PM molecule was found to have a strong effect on the adsorption of PM on activated carbon and caused two major adsorption behaviors, "propensity" and "directionality". The PM molecule, as well as other oxygenated VOCs, tended to be adsorbed on areas of activated carbon with similar polarity, which caused its adsorption "propensity". However, the cross-sectional area (55.95 Å2) of the hydrophilic hydroxy groups on a PM molecule is **** larger than that of the hydrophobic methoxy groups (29.46 Å2), which leads to the adsorption "directionality", such that the amount of PM adsorption on activated carbon was affected by whether PM molecules were adsorbed by their hydrophilic hydroxy groups or hydrophobic methoxy groups over the same adsorption area. Additionally, a predictive model based on the properties of activated carbon and the PM molecule was proposed and further verified. Severe dust events have occurred frequently in arid regions, which greatly impacted air quality, climate, and public health. The Middle East is one of the areas in the world impacted by intense dust storms. We investigated the characteristics of airborne dust levels in five Middle Eastern countries (Kuwait, Iraq, Iran, Saudi Arabia, and Syria) from 2001 to 2017. https://www.selleckchem.com/products/mcc950-sodium-salt.html Surface level dust concentrations were determined using the Modern-Era Retrospective analysis for Research and Applications version 2. Kuwait was selected as an example to assess sources and other factors influencing dust levels in arid regions. We performed backward trajectory analysis to identify the dust transport pathways. We quantitatively assessed the impacts of meteorological parameters along with the Normalized Difference Vegetation Index (NDVI). Dust levels in Kuwait were higher than the other four countries, and had a distinct seasonal pattern, with the highest in summer and the lowest in winter. Our results showed that dust levels in Kuwait in January were influenced largely by local emissions, whereas in June they were affected more by emissions attributable to long-distance transport. There were significant positive associations between wind speed in the five countries, particularly Iraq, with dust levels in Kuwait, indicating the impact of nearby desert areas. Significant negative associations were observed between NDVI in Kuwait, Iraq, and Saudi Arabia with dust levels in Kuwait. Our result highlights that climatic variations and vegetation conditions are associated with changes in dust levels in arid regions.
    2 m) in average levels of shallow groundwater systems, which may occur in Northern Europe within the coming two decades, can increase mass flows of metals through groundwater by a factor of 2-10. There is a similar risk of increased metal mobilization in regions subject to increased (seasonal or event-scale) amplitude of groundwater levels fluctuations. Neglecting groundwater level dynamics in predictive models can thus lead to considerable and systematic underestimation of metal mobilization and future changes. More generally, our results suggest that the key to quantifying impacts of climate change on metal mobilization is to understand how the contact between groundwater and the highly water-conducting and geochemically heterogeneous topsoil layers will change in the future. Polychlorinated dibenzo-p-dioxins and dibenzofurans are a group of chemically-related pollutants categorically known as dioxins. Some of their chlorinated congeners are among the most hazardous pollutants that persist in the environment. This persistence is due in part to the limited number of bacteria capable of metabolizing these compounds, but also to their limited bioavailability in soil. We used Sphingomonas wittichii strain RW1 (RW1), one of the few strains able to grow on dioxin, to characterize its ability to respond to and degrade clay-bound dioxin. We found that RW1 grew on and completely degraded dibenzo-p-dioxin (DD) intercalated into the smectite clay saponite (SAP). To characterize the effects of DD sorption on RW1 gene expression, we compared transcriptomes of RW1 grown with either free crystalline DD or DD intercalated clay, i.e. sandwiched between the clay interlayers (DDSAP). Free crystalline DD appeared to cause greater expression of toxicity and stress related functions. Genes coding for heat shock proteins, chaperones, as well as genes involved in DNA repair, and efflux were up-regulated during growth on crystalline dioxin compared to growth on intercalated dioxin. In contrast, growth on intercalated dioxin up-regulated genes that might be important in recognition and uptake mechanisms, as well as surface interaction/attachment/biofilm formation such as extracellular solute-binding protein and LuxR. These differences in gene expression may reflect the underlying adaptive mechanisms by which RW1 cells sense and deploy pathways to access dioxin intercalated into clay. These data show that intercalated DD remains bioavailable to the degrading bacterium with implications for bioremediation alternatives. Dissolved organic nitrogen (DON) with a mixture of various organic nitrogen (N) is recognized as an emerging groundwater contaminant. Investigating the behavior and mechanism of DON sorption onto clay minerals, which are key components of vadose zone media, is crucial to evaluating its leaching potential. Considering the interactions among multiple DON compounds (DONs) may influence their sorption behaviors, the sorption of three typical DONs (amino acid, protein and urea) to clay minerals in single-, binary- and ternary-solute systems were explored, respectively. In addition, a combination of multiple methods, including physiochemical characterization, Fourier Transform Infrared Spectroscopy (FTIR), X-ray diffraction (XRD) and pH variation analysis, were used to provide insight into the governing mechanisms. Results indicated that the sorption kinetics and isotherms of single systems were well-fitted by pseudo-second-order and Freundlich isotherm models, respectively. The mechanisms involved in the sorption DONs in the vadose zone and their leachability into groundwater. In most investigations of adsorption process, the effects of adsorbate properties on adsorption capacity were often not obtain enough attention, compared with the properties of adsorbent. Apart from the polarity, and the boiling point of adsorbate, the molecular space conformation is also play an important role in its adsorption behavior on porous materials. In this work, two series of orientation-designed activated carbon were used to study the microscopic adsorption behavior of amphiphilic propylene glycol methyl ether (PM) gas. The spatial conformation of the PM molecule was found to have a strong effect on the adsorption of PM on activated carbon and caused two major adsorption behaviors, "propensity" and "directionality". The PM molecule, as well as other oxygenated VOCs, tended to be adsorbed on areas of activated carbon with similar polarity, which caused its adsorption "propensity". However, the cross-sectional area (55.95 Å2) of the hydrophilic hydroxy groups on a PM molecule is much larger than that of the hydrophobic methoxy groups (29.46 Å2), which leads to the adsorption "directionality", such that the amount of PM adsorption on activated carbon was affected by whether PM molecules were adsorbed by their hydrophilic hydroxy groups or hydrophobic methoxy groups over the same adsorption area. Additionally, a predictive model based on the properties of activated carbon and the PM molecule was proposed and further verified. Severe dust events have occurred frequently in arid regions, which greatly impacted air quality, climate, and public health. The Middle East is one of the areas in the world impacted by intense dust storms. We investigated the characteristics of airborne dust levels in five Middle Eastern countries (Kuwait, Iraq, Iran, Saudi Arabia, and Syria) from 2001 to 2017. https://www.selleckchem.com/products/mcc950-sodium-salt.html Surface level dust concentrations were determined using the Modern-Era Retrospective analysis for Research and Applications version 2. Kuwait was selected as an example to assess sources and other factors influencing dust levels in arid regions. We performed backward trajectory analysis to identify the dust transport pathways. We quantitatively assessed the impacts of meteorological parameters along with the Normalized Difference Vegetation Index (NDVI). Dust levels in Kuwait were higher than the other four countries, and had a distinct seasonal pattern, with the highest in summer and the lowest in winter. Our results showed that dust levels in Kuwait in January were influenced largely by local emissions, whereas in June they were affected more by emissions attributable to long-distance transport. There were significant positive associations between wind speed in the five countries, particularly Iraq, with dust levels in Kuwait, indicating the impact of nearby desert areas. Significant negative associations were observed between NDVI in Kuwait, Iraq, and Saudi Arabia with dust levels in Kuwait. Our result highlights that climatic variations and vegetation conditions are associated with changes in dust levels in arid regions.
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  • Background Urine cytology is a noninvasive and inexpensive method; however, it is limited in low sensitivity for detecting and monitoring urothelial carcinoma (UC). To overcome limitation of cytology, several tests using urine samples have been attempted that immunocytochemical staining is an inexpensive and easy to perform ancillary technique. Dual immunocytochemical staining for p53 and cytokeratin 20 (CK20) is assessed in liquid-based urine cytology slides. https://www.selleckchem.com/products/nd-630.html Materials and Methods Liquid-based urine cytology samples collected between 2008 and 2013 and matched follow-up biopsy samples of high-grade UC (HGUC) (n = 44) and low-grade UC (LGUC) (n = 14) were analyzed. Results Urine cytology showing atypical cells was subjected to dual-color immunostaining for p53 and CK20. The sensitivity of urine cytology combined with p53 and CK20 immunostaining was 77.3% in HGUC and 52.9% in LGUC. Of 20 cases diagnosed with atypia by urine cytology, 13 (65%) were positive for p53 or CK20. Dual immunocytochemical staining for p53/CK20 improved the diagnostic accuracy of urine cytology. Conclusions The present results indicate that cytomorphology combined with p53/CK20 immunostaining is useful for the detection of HGUC and LGUC. ©2020 Cytopathology Foundation Inc, Published by Scientific Scholar.The request form accompanying any sample to a clinical laboratory constitutes an important communication tool between the clinician and the laboratory personnel. **** has been written about the inadequacy of pertinent clinical data on the request slips for hematology and biochemistry tests and its impact on the subsequent test interpretation and error liability. Although the cytology laboratories, including those performing cervical cytology, have to deal with a similar problem of lack of clinical information critical to the proper interpretation of cytomorphologic features, the issue has not been attended to or reported adequately in the literature. This article attempts to explore this topic of inadequate clinical data on Pap test request form from multiple perspectives and suggest possible ways to circumvent this age-old problem. These recommendations may be tailor-made and adopted as per the individual laboratory's logistics. ©2020 Cytopathology Foundation Inc, Published by Scientific Scholar.As important components of positive and negative reinforcement, locomotor sensitization and withdrawal anxiety following repeated exposure to nicotine (NIC) constitute crucial risk factors for relapse to NIC use after abstinence. Glycyrrhiza radix (G. radix), an important tonic used in traditional Oriental medicine, has not only anxiolytic effects but also reduces NIC-induced locomotor sensitization. Isoliquiritigenin (ISL), a bioactive ingredient of G. radix, also exhibits neuropharmacological effects, including anxiolytic action. Previously, we reported that ISL suppressed cocaine-induced extracellular dopamine release in the nucleus accumbens shell (NaccSh) and attenuated methamphetamine-induced neurotoxicity. The present study was performed to evaluate the effects of ISL on both NIC withdrawal anxiety and locomotor sensitization. Adult male rats received subcutaneous administration of NIC hydrogen tartrate (0.4 mg/kg, twice a day) for 7 days followed by 4 days of withdrawal. During the period of NIC withdCopyright © 2020 Yuhua Wang et al.Hypothyroidism frequently causes cardiopulmonary dysfunction, such as heart failure and respiratory and metabolic deficiencies. This study investigated the effects of Chinese herbal formula B307 on thyroidectomy-induced cardiopulmonary exercise dysfunction in rats. Twenty male rats were equally divided into four groups negative control with sham treatment, positive control with oral B307 treatment only, thyroidectomy treatment only, and thyroidectomy with B307 posttreatment groups. The feeding dose of B307 was 50 mg/kg per day for 14 days. We examined and then compared the thyroid-stimulating hormone (TSH), free triiodothyronine (T3), free thyroxine (T4), and reactive oxygen species (ROS) from the blood of these four groups. Also, we compared the body weight, neck subcutaneous blood flow, cardiac ejection function, cardiopulmonary exercise function of oxygen consumption (VO2), carbon dioxide production (VCO2), and respiratory quotient (RQ = VCO2/VO2) among the four groups. Our results indicated that thyroidectomized rats had significantly decreased body weight, neck subcutaneous blood flow, cardiac ejection function, serum T3 and T4, and VO2 and VCO2, but had significantly increased ROS and TSH levels and RQ values compared with sham rats (P less then 0.01-0.05). In addition, thyroidectomized rats receiving oral B307 treatment had significantly increased body weight, neck subcutaneous blood flow, cardiac ejection function, and VO2, but significantly decreased ROS and TSH levels and VCO2 and RQ values compared with thyroidectomized rats (P less then 0.01-0.05). We suggest that the B307 could be a protective and beneficial alternative treatment for thyroidectomy-induced cardiopulmonary exercise dysfunction. Copyright © 2020 Tai-Yuan Chuang et al.Background Dingji Fumai decoction (DFD) is used to treat ventricular arrhythmia, and it has provided a very good curative effect. However, its cellular electrophysiological mechanism is unknown. Methods Electrocardiogram was recorded, and oxidative stress response and ion-channel-related molecules were detected in rats with barium chloride- and aconitine-induced ventricular arrhythmia. Moreover, whole-cell patch-clamp assay was used to investigate the inhibitory effect of DFD on Nav1.5 in Chinese hamster ovary cells. Results DFD prolonged the occurrence time and shortened the duration of ventricular arrhythmia, decreased the malondialdehyde and increased the superoxide dismutase, and alleviated the activation of Na+-K+-ATPase and connexin-43. DFD suppressed Nav1.5dose-dependently with an IC50 of 24.0 ± 2.4 mg/mL. Conclusions The clinical antiarrhythmic mechanisms of DFD are based on its antioxidant potential, alleviation of Na+-K+-ATPase and connexin-43, and class I antiarrhythmic properties by suppressing Nav1.
    Background Urine cytology is a noninvasive and inexpensive method; however, it is limited in low sensitivity for detecting and monitoring urothelial carcinoma (UC). To overcome limitation of cytology, several tests using urine samples have been attempted that immunocytochemical staining is an inexpensive and easy to perform ancillary technique. Dual immunocytochemical staining for p53 and cytokeratin 20 (CK20) is assessed in liquid-based urine cytology slides. https://www.selleckchem.com/products/nd-630.html Materials and Methods Liquid-based urine cytology samples collected between 2008 and 2013 and matched follow-up biopsy samples of high-grade UC (HGUC) (n = 44) and low-grade UC (LGUC) (n = 14) were analyzed. Results Urine cytology showing atypical cells was subjected to dual-color immunostaining for p53 and CK20. The sensitivity of urine cytology combined with p53 and CK20 immunostaining was 77.3% in HGUC and 52.9% in LGUC. Of 20 cases diagnosed with atypia by urine cytology, 13 (65%) were positive for p53 or CK20. Dual immunocytochemical staining for p53/CK20 improved the diagnostic accuracy of urine cytology. Conclusions The present results indicate that cytomorphology combined with p53/CK20 immunostaining is useful for the detection of HGUC and LGUC. ©2020 Cytopathology Foundation Inc, Published by Scientific Scholar.The request form accompanying any sample to a clinical laboratory constitutes an important communication tool between the clinician and the laboratory personnel. Much has been written about the inadequacy of pertinent clinical data on the request slips for hematology and biochemistry tests and its impact on the subsequent test interpretation and error liability. Although the cytology laboratories, including those performing cervical cytology, have to deal with a similar problem of lack of clinical information critical to the proper interpretation of cytomorphologic features, the issue has not been attended to or reported adequately in the literature. This article attempts to explore this topic of inadequate clinical data on Pap test request form from multiple perspectives and suggest possible ways to circumvent this age-old problem. These recommendations may be tailor-made and adopted as per the individual laboratory's logistics. ©2020 Cytopathology Foundation Inc, Published by Scientific Scholar.As important components of positive and negative reinforcement, locomotor sensitization and withdrawal anxiety following repeated exposure to nicotine (NIC) constitute crucial risk factors for relapse to NIC use after abstinence. Glycyrrhiza radix (G. radix), an important tonic used in traditional Oriental medicine, has not only anxiolytic effects but also reduces NIC-induced locomotor sensitization. Isoliquiritigenin (ISL), a bioactive ingredient of G. radix, also exhibits neuropharmacological effects, including anxiolytic action. Previously, we reported that ISL suppressed cocaine-induced extracellular dopamine release in the nucleus accumbens shell (NaccSh) and attenuated methamphetamine-induced neurotoxicity. The present study was performed to evaluate the effects of ISL on both NIC withdrawal anxiety and locomotor sensitization. Adult male rats received subcutaneous administration of NIC hydrogen tartrate (0.4 mg/kg, twice a day) for 7 days followed by 4 days of withdrawal. During the period of NIC withdCopyright © 2020 Yuhua Wang et al.Hypothyroidism frequently causes cardiopulmonary dysfunction, such as heart failure and respiratory and metabolic deficiencies. This study investigated the effects of Chinese herbal formula B307 on thyroidectomy-induced cardiopulmonary exercise dysfunction in rats. Twenty male rats were equally divided into four groups negative control with sham treatment, positive control with oral B307 treatment only, thyroidectomy treatment only, and thyroidectomy with B307 posttreatment groups. The feeding dose of B307 was 50 mg/kg per day for 14 days. We examined and then compared the thyroid-stimulating hormone (TSH), free triiodothyronine (T3), free thyroxine (T4), and reactive oxygen species (ROS) from the blood of these four groups. Also, we compared the body weight, neck subcutaneous blood flow, cardiac ejection function, cardiopulmonary exercise function of oxygen consumption (VO2), carbon dioxide production (VCO2), and respiratory quotient (RQ = VCO2/VO2) among the four groups. Our results indicated that thyroidectomized rats had significantly decreased body weight, neck subcutaneous blood flow, cardiac ejection function, serum T3 and T4, and VO2 and VCO2, but had significantly increased ROS and TSH levels and RQ values compared with sham rats (P less then 0.01-0.05). In addition, thyroidectomized rats receiving oral B307 treatment had significantly increased body weight, neck subcutaneous blood flow, cardiac ejection function, and VO2, but significantly decreased ROS and TSH levels and VCO2 and RQ values compared with thyroidectomized rats (P less then 0.01-0.05). We suggest that the B307 could be a protective and beneficial alternative treatment for thyroidectomy-induced cardiopulmonary exercise dysfunction. Copyright © 2020 Tai-Yuan Chuang et al.Background Dingji Fumai decoction (DFD) is used to treat ventricular arrhythmia, and it has provided a very good curative effect. However, its cellular electrophysiological mechanism is unknown. Methods Electrocardiogram was recorded, and oxidative stress response and ion-channel-related molecules were detected in rats with barium chloride- and aconitine-induced ventricular arrhythmia. Moreover, whole-cell patch-clamp assay was used to investigate the inhibitory effect of DFD on Nav1.5 in Chinese hamster ovary cells. Results DFD prolonged the occurrence time and shortened the duration of ventricular arrhythmia, decreased the malondialdehyde and increased the superoxide dismutase, and alleviated the activation of Na+-K+-ATPase and connexin-43. DFD suppressed Nav1.5dose-dependently with an IC50 of 24.0 ± 2.4 mg/mL. Conclusions The clinical antiarrhythmic mechanisms of DFD are based on its antioxidant potential, alleviation of Na+-K+-ATPase and connexin-43, and class I antiarrhythmic properties by suppressing Nav1.
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  • is of the isolated samples were compared with the World database; all isolates were found to be 100% genotype B and 99% genotype E. In this study, the sequence analysis of the ompA gene of C.psittaci from domestic pigeon feces was determined for the first time in Turkey. Although the presence of C.psittaci in domestic pigeons is low, it is a zoonotic bacterium and is important for the public health.Sexually transmitted infections (STIs) are important as a public health problem all over the world. There are some difficulties in prevention and control programs of STIs due to clinical and laboratory diagnostic problems.The most common STIs are Chlamydia trachomatis infections, trichomoniasis and gonorrhea. The study aimed to investigate the direct microscopic examination, culture and polymerase chain reaction (PCR) tests in the diagnosis of Trichomonas vaginalis infection; to determine other microbiological agents that may cause vaginal discharge and to evaluate the various social variables in women with vaginal discharge admitted to the outpatient clinic of Obstetrics and Gynecology in Akdeniz University Hospital. Two hundred and fifteen patients were enrolled in the study. The socio-demographic features of the patients were recorded. Vaginal/endocervical swab specimens taken from patients were evaluated by microscopic examination. Swab specimens were inoculated into blood agar, MacConkey agar and chocolaigher in women who have had two or more pregnancies (p less then 0.05). In our study, T.vaginalis together with N.gonorrhoeae and C.trachomatis were investigated by PCR method in women with vaginal discharge. The use of multiplex PCR test allowed simultaneous investigation of multiple pathogens in the patient samples.Micafungin is recommended especially in patients with liver and kidney failure and in the presence of other side effects due to antifungals apart from its known priority indications such as invasive candidiasis. The aim of this study was to evaluate the children who have received micafungin treatment. In the study, 125 children who were hospitalized in the pediatric wards and intensive care units of our hospital and had used micafungin between November 2016 and January 2019 were analyzed retrospectively. Clinical data, micafungin indication, blood values on the first and fourth days of the treatment, side effects of the drug and efficacy were evaluated. Sixty percent (75/125) of the patients were male and the mean age of all the patients were 58 ± 67 (0-215, 30) months. Approximately half of the cases (48%) had malignancy and 13% of them were premature. Sixty-two percent (n= 37) of the malignencies were hematological (27 acute lymphocytic leukemia, nine acute myeloid leukemia, one myelodysplastic syndrome) anficant side effects were observed in any of the patients. Our study showed that micafungin could be a safe and effective option in pediatric cases including newborns with high liver and kidney function tests.Anti-HCV and HCV RNA tests are used in laboratory diagnosis of hepatitis C virus (HCV) infections. False positive results are frequently observed in anti-HCV tests used as screening tests in societies with low prevalence of HCV. https://www.selleckchem.com/products/4-hydroxynonenal.html The HCV RNA test, which is a confirmatory test, is not performed in every laboratory because it is a high-cost and high-tech test, which can lead to delay in the diagnosis and treatment of patients. In this study, it was aimed to obtain an optimal anti-HCV S/CO value in our laboratory for demonstrating true antibody positivity and viremia in patients by analyzing the relationship between anti-HCV, alanine aminotransferase (ALT) and HCV RNA using retrospective data. Between July 2014 and July 2017, 754.190 anti-HCV tests were performed. Patients aged 18 years or older who were reactive with anti-HCV and those with simultaneous HCV RNA and ALT prompts were included in the study. The second generation CMIA (Abbott, USA) method was used for anti-HCV detection. For quantitative HCV RNA anaesenting for screening can be predicted without waiting for the HCV RNA result. In anti-HCV reactivities determined above 7.13, the possibility of absence of viremia should be considered due to the low positive predictive value.Chronic hepatitis B (CHB) is an important public health problem in the world and Turkey. The aim of this study was to evaluate the histological, virological, serological and biochemical response rates in CHB patients receiving tenofovir or entecavir therapy. Control liver biopsies were performed on patients who received tenofovir or entecavir therapy for one year or longer. Histopathological grading was scored according to the modified Knodell system. Eighty-seven CHB patients were included in this study, 56 patients were receiving tenofovir and 31 patients were receiving entecavir therapy. Patients in two treatment groups were similar in terms of baseline parameters (p> 0.05). At the end of the treatment, there was a significant decrease in mean values of HBV DNA, alanine aminotransferase and necroinflammatory scores for both groups (p 0.05). Similar histological, virological, serological and biochemical responses were obtained in patients with CHB receving tenofovir and entecavir treatments. Further studies involving a large number of patients receiving long-term therapy should be done to understand the effects of antiviral treatments on healing of liver histology.While acyclovir, a nucleoside analogue, is widely used for herpes simplex virus type 1 (HSV-1), emergence of drug-resistant viruses due to frequent usage of this class of medicines, and their toxic side effects require exploring novel active molecules. Despite the studies on developing synthetic molecules in medical sciences and pharmacology, herbs as a natural source of biologically-active compounds remain popular. In this in vitro study, olive leaf extract (OLE) and propolis alone or in combination with acyclovir were investigated for their antiviral efficacy in HSV-1.Toxic doses of OLE, propolis, and dimethyl sulfoxide, propolis diluent, for Hep-2 (ATCC, CCL-23) cells were determined by conventional cell culture. Using "endpoint" method, the viral dose infecting half of the cell culture (TCID50) was calculated, and viral quantity was determined with Spearman-Karber method. Antiviral effects of OLE and propolis on HSV-1 were investigated by conventional cell culture and real-time cell analysis (RTCA). Combinations of the two extracts with one another and with acyclovir were evaluated by RTCA.
    is of the isolated samples were compared with the World database; all isolates were found to be 100% genotype B and 99% genotype E. In this study, the sequence analysis of the ompA gene of C.psittaci from domestic pigeon feces was determined for the first time in Turkey. Although the presence of C.psittaci in domestic pigeons is low, it is a zoonotic bacterium and is important for the public health.Sexually transmitted infections (STIs) are important as a public health problem all over the world. There are some difficulties in prevention and control programs of STIs due to clinical and laboratory diagnostic problems.The most common STIs are Chlamydia trachomatis infections, trichomoniasis and gonorrhea. The study aimed to investigate the direct microscopic examination, culture and polymerase chain reaction (PCR) tests in the diagnosis of Trichomonas vaginalis infection; to determine other microbiological agents that may cause vaginal discharge and to evaluate the various social variables in women with vaginal discharge admitted to the outpatient clinic of Obstetrics and Gynecology in Akdeniz University Hospital. Two hundred and fifteen patients were enrolled in the study. The socio-demographic features of the patients were recorded. Vaginal/endocervical swab specimens taken from patients were evaluated by microscopic examination. Swab specimens were inoculated into blood agar, MacConkey agar and chocolaigher in women who have had two or more pregnancies (p less then 0.05). In our study, T.vaginalis together with N.gonorrhoeae and C.trachomatis were investigated by PCR method in women with vaginal discharge. The use of multiplex PCR test allowed simultaneous investigation of multiple pathogens in the patient samples.Micafungin is recommended especially in patients with liver and kidney failure and in the presence of other side effects due to antifungals apart from its known priority indications such as invasive candidiasis. The aim of this study was to evaluate the children who have received micafungin treatment. In the study, 125 children who were hospitalized in the pediatric wards and intensive care units of our hospital and had used micafungin between November 2016 and January 2019 were analyzed retrospectively. Clinical data, micafungin indication, blood values on the first and fourth days of the treatment, side effects of the drug and efficacy were evaluated. Sixty percent (75/125) of the patients were male and the mean age of all the patients were 58 ± 67 (0-215, 30) months. Approximately half of the cases (48%) had malignancy and 13% of them were premature. Sixty-two percent (n= 37) of the malignencies were hematological (27 acute lymphocytic leukemia, nine acute myeloid leukemia, one myelodysplastic syndrome) anficant side effects were observed in any of the patients. Our study showed that micafungin could be a safe and effective option in pediatric cases including newborns with high liver and kidney function tests.Anti-HCV and HCV RNA tests are used in laboratory diagnosis of hepatitis C virus (HCV) infections. False positive results are frequently observed in anti-HCV tests used as screening tests in societies with low prevalence of HCV. https://www.selleckchem.com/products/4-hydroxynonenal.html The HCV RNA test, which is a confirmatory test, is not performed in every laboratory because it is a high-cost and high-tech test, which can lead to delay in the diagnosis and treatment of patients. In this study, it was aimed to obtain an optimal anti-HCV S/CO value in our laboratory for demonstrating true antibody positivity and viremia in patients by analyzing the relationship between anti-HCV, alanine aminotransferase (ALT) and HCV RNA using retrospective data. Between July 2014 and July 2017, 754.190 anti-HCV tests were performed. Patients aged 18 years or older who were reactive with anti-HCV and those with simultaneous HCV RNA and ALT prompts were included in the study. The second generation CMIA (Abbott, USA) method was used for anti-HCV detection. For quantitative HCV RNA anaesenting for screening can be predicted without waiting for the HCV RNA result. In anti-HCV reactivities determined above 7.13, the possibility of absence of viremia should be considered due to the low positive predictive value.Chronic hepatitis B (CHB) is an important public health problem in the world and Turkey. The aim of this study was to evaluate the histological, virological, serological and biochemical response rates in CHB patients receiving tenofovir or entecavir therapy. Control liver biopsies were performed on patients who received tenofovir or entecavir therapy for one year or longer. Histopathological grading was scored according to the modified Knodell system. Eighty-seven CHB patients were included in this study, 56 patients were receiving tenofovir and 31 patients were receiving entecavir therapy. Patients in two treatment groups were similar in terms of baseline parameters (p> 0.05). At the end of the treatment, there was a significant decrease in mean values of HBV DNA, alanine aminotransferase and necroinflammatory scores for both groups (p 0.05). Similar histological, virological, serological and biochemical responses were obtained in patients with CHB receving tenofovir and entecavir treatments. Further studies involving a large number of patients receiving long-term therapy should be done to understand the effects of antiviral treatments on healing of liver histology.While acyclovir, a nucleoside analogue, is widely used for herpes simplex virus type 1 (HSV-1), emergence of drug-resistant viruses due to frequent usage of this class of medicines, and their toxic side effects require exploring novel active molecules. Despite the studies on developing synthetic molecules in medical sciences and pharmacology, herbs as a natural source of biologically-active compounds remain popular. In this in vitro study, olive leaf extract (OLE) and propolis alone or in combination with acyclovir were investigated for their antiviral efficacy in HSV-1.Toxic doses of OLE, propolis, and dimethyl sulfoxide, propolis diluent, for Hep-2 (ATCC, CCL-23) cells were determined by conventional cell culture. Using "endpoint" method, the viral dose infecting half of the cell culture (TCID50) was calculated, and viral quantity was determined with Spearman-Karber method. Antiviral effects of OLE and propolis on HSV-1 were investigated by conventional cell culture and real-time cell analysis (RTCA). Combinations of the two extracts with one another and with acyclovir were evaluated by RTCA.
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  • Bergenin, 11-O-galloylbergenin, arbutin, catechin-3-O-gallate, and other components play a synergistic role in treating osteoarthritis. This study analyzed the chemical components of Bergenia purpurascens and preliminarily revealed potential mechanisms of treating osteoarthritis, providing a basis for further evaluating the drug's efficacy.Porcine sapelovirus (PSV) is a causative agent of acute diarrhoea, pneumonia and reproductive disorders in *****. Since PSV infection interrupts the growth of other viruses due to its high replication capability in cell culture, the prevention of PSV replication is a keystone to the isolation of non-PSV agents from PSV-contaminated samples. In the present study, we established the PSV infection-resistant cell line N1380 and isolated three mammalian orthoreoviruses (MRV) strains, sR1521, sR1677 and sR1590, from ***** in Taiwan. These Taiwanese isolates induced an extensive cytopathic effect in N1380 cells upon infection. The complete and empty virus particles were purified from the cell culture supernatants. Next-generation sequencing analyses revealed that the complete virus particles contained 10 segments, including 3 large (L1, L2 and L3), 3 medium (M1, M2 and M3) and 4 small (S1, S2, S3 and S4) segments. In contrast, the empty virus particles without genome were non-infectious. Phylogenetic analyses revealed that the Taiwanese strains belong to serotype 2 MRV (MRV2). We established an ELISA for the detection of IgG antibody against MRV2 by using the empty virus particles as the antigen. A total of 540 ***** and 95 wild boar serum samples were collected in Japan, and the positive rates were 100% and 52.6%, respectively. These results demonstrated that MRV infection occurred frequently in both ***** and wild boar in Japan. We established a cell line that is efficient for the isolation of MRV, and the ELISA based on the naturally occurring empty particles would be of great value for the surveillance of MRV-related diseases.Objectives To explore male human papillomavirus (HPV) contemporary genotyping epidemiology and correlations to peniscopy, cytology, and histopatology. Methods Medical records of patients who had been submitted to HPV infection screening with genotyping, peniscopy, cytology, and histopathology in a period of 2 years were reviewed. Frequency analysis and correlations between the diagnostic tools were established. Results Genotype of 1132 men resulted in 69.2% (784) positivity for HPV DNA, 78% classified as high risk of oncogenesis. Co-infections occurred in 429 (54.7%) and the most frequently identified types were HPV-6, HPV-42, and HPV-16, in 133 (17%), 94 (12%), and 86 (11%) patients, respectively. Positive/negative predictive values of peniscopy, cytology, and histopathology were 83/31%, 92/32%, and 87/33%, respectively. As a result, though significant, the correlations between genotype and non-molecular tests were poor. https://www.selleckchem.com/products/talabostat.html Conclusions In the current contemporary representative male cohort, over two thirds are positive for human HPV DNA, 78% of high risk and with over half co-infections. Though significant, its correlation with non-molecular tests is poor and while the positive predictive values of peniscopy, cytology, and histopatology are between 83% and 92%, their negative predictive values are as low as 31% to 33%.It has been found that the non-B form DNA structures, like G-quadruplex (G4) and i-motif, are involved in many important biological processes. Our previous study showed that the silkworm transcription factor BmLARK binds to the G4 structure in the promoter of the transcription factor BmPOUM2 and regulates its promoter activity. However, the binding mechanism between BmLARK and BmPOUM2 G4 structure remains unclear. In this study, binding domains and key amino acid residues involved in the interaction between BmLARK and BmPOUM2 G4 were studied. The EMSA results indicated that the two RNA-recognition motifs (RRM) of BmLARK are simultaneously required for the binding with the G4 structure. Either RRM1 or RRM2 alone could not bind with the G4 structure. The zinc-finger motif was not involved in the binding. A series of mutant proteins with specific amino acid mutations were expressed and used to identify the key amino acid residues involving the interaction. The results indicated that β sheets, especially the β1 and β3 sheets, in the RRM domains of BmLARK played critical roles in the binding with the G4 structure. Several amino acid mutations of RRM1/2 in ribonucleoprotein domain 1 (RNP1) (motif in β3 strand) and RNP2 (motif in β1 strand) caused loss of binding ability, indicating that these amino acids are the key sites for the binding. All the results suggest that RRM domains, particularly it's the RNP1 and RNP2 motifs, play important roles not only in RNA recognition, but also in the G4 structure binding. This article is protected by copyright. All rights reserved.2-Formyl-2'-deoxyadenosine triphosphate (dCHO ATP) was synthesized and tested as a substrate in enzymatic synthesis of DNA modified in the minor groove with a reactive aldehyde group. The multistep synthesis of dCHO ATP was based on the preparation of protected 2-dihydroxyethyl-2'-deoxyadenosine intemediate, which was triphosphorylated and converted to aldehyde through oxidative cleavage. The dCHO ATP triphosphate was a moderate substrate for KOD XL DNA polymerase, and was used for enzymatic synthesis of some sequences using primer extension (PEX). On the other hand, longer sequences (31-mer) with higher number of modifications, or sequences with modifications at adjacent positions did not give full extension. Single-nucleotide extension followed by PEX was used for site-specific incorporation of one aldehyde-linked adenosine into a longer 49-mer sequence. The reactive formyl group was used for cross-linking with peptides and proteins using reductive amination and for fluorescent labelling through oxime formation with an AlexaFluor647-linked hydroxylamine.Klinefelter syndrome (KS; 47,XXY) is the most common sex chromosome abnormality in males (150 per 100,000 males). The condition leads to hypergonadotropic hypogonadism and ever since the condition was described approximately 80 years ago, testosterone treatment has been the cornerstone in care for individuals with KS. However, KS is associated with an array of health-related and socioeconomic challenges and it is becoming progressively clear that proper care for boys and men with KS reaches far beyond simply supplementing with testosterone. There are no widely implemented guidelines for KS care, and studies investigating crucial aspects of testosterone treatment in individuals with KS, including both beneficial and potentially adverse effects, have only begun to emerge during the last decades. For this descriptive review, we present an overview of literature describing health-related outcomes of testosterone treatment in KS and outline the clinical applications of testosterone treatment in KS. Collectively, beneficial effects of testosterone treatment on overall health in KS are described with few apparent adverse effects.
    Bergenin, 11-O-galloylbergenin, arbutin, catechin-3-O-gallate, and other components play a synergistic role in treating osteoarthritis. This study analyzed the chemical components of Bergenia purpurascens and preliminarily revealed potential mechanisms of treating osteoarthritis, providing a basis for further evaluating the drug's efficacy.Porcine sapelovirus (PSV) is a causative agent of acute diarrhoea, pneumonia and reproductive disorders in swine. Since PSV infection interrupts the growth of other viruses due to its high replication capability in cell culture, the prevention of PSV replication is a keystone to the isolation of non-PSV agents from PSV-contaminated samples. In the present study, we established the PSV infection-resistant cell line N1380 and isolated three mammalian orthoreoviruses (MRV) strains, sR1521, sR1677 and sR1590, from swine in Taiwan. These Taiwanese isolates induced an extensive cytopathic effect in N1380 cells upon infection. The complete and empty virus particles were purified from the cell culture supernatants. Next-generation sequencing analyses revealed that the complete virus particles contained 10 segments, including 3 large (L1, L2 and L3), 3 medium (M1, M2 and M3) and 4 small (S1, S2, S3 and S4) segments. In contrast, the empty virus particles without genome were non-infectious. Phylogenetic analyses revealed that the Taiwanese strains belong to serotype 2 MRV (MRV2). We established an ELISA for the detection of IgG antibody against MRV2 by using the empty virus particles as the antigen. A total of 540 swine and 95 wild boar serum samples were collected in Japan, and the positive rates were 100% and 52.6%, respectively. These results demonstrated that MRV infection occurred frequently in both swine and wild boar in Japan. We established a cell line that is efficient for the isolation of MRV, and the ELISA based on the naturally occurring empty particles would be of great value for the surveillance of MRV-related diseases.Objectives To explore male human papillomavirus (HPV) contemporary genotyping epidemiology and correlations to peniscopy, cytology, and histopatology. Methods Medical records of patients who had been submitted to HPV infection screening with genotyping, peniscopy, cytology, and histopathology in a period of 2 years were reviewed. Frequency analysis and correlations between the diagnostic tools were established. Results Genotype of 1132 men resulted in 69.2% (784) positivity for HPV DNA, 78% classified as high risk of oncogenesis. Co-infections occurred in 429 (54.7%) and the most frequently identified types were HPV-6, HPV-42, and HPV-16, in 133 (17%), 94 (12%), and 86 (11%) patients, respectively. Positive/negative predictive values of peniscopy, cytology, and histopathology were 83/31%, 92/32%, and 87/33%, respectively. As a result, though significant, the correlations between genotype and non-molecular tests were poor. https://www.selleckchem.com/products/talabostat.html Conclusions In the current contemporary representative male cohort, over two thirds are positive for human HPV DNA, 78% of high risk and with over half co-infections. Though significant, its correlation with non-molecular tests is poor and while the positive predictive values of peniscopy, cytology, and histopatology are between 83% and 92%, their negative predictive values are as low as 31% to 33%.It has been found that the non-B form DNA structures, like G-quadruplex (G4) and i-motif, are involved in many important biological processes. Our previous study showed that the silkworm transcription factor BmLARK binds to the G4 structure in the promoter of the transcription factor BmPOUM2 and regulates its promoter activity. However, the binding mechanism between BmLARK and BmPOUM2 G4 structure remains unclear. In this study, binding domains and key amino acid residues involved in the interaction between BmLARK and BmPOUM2 G4 were studied. The EMSA results indicated that the two RNA-recognition motifs (RRM) of BmLARK are simultaneously required for the binding with the G4 structure. Either RRM1 or RRM2 alone could not bind with the G4 structure. The zinc-finger motif was not involved in the binding. A series of mutant proteins with specific amino acid mutations were expressed and used to identify the key amino acid residues involving the interaction. The results indicated that β sheets, especially the β1 and β3 sheets, in the RRM domains of BmLARK played critical roles in the binding with the G4 structure. Several amino acid mutations of RRM1/2 in ribonucleoprotein domain 1 (RNP1) (motif in β3 strand) and RNP2 (motif in β1 strand) caused loss of binding ability, indicating that these amino acids are the key sites for the binding. All the results suggest that RRM domains, particularly it's the RNP1 and RNP2 motifs, play important roles not only in RNA recognition, but also in the G4 structure binding. This article is protected by copyright. All rights reserved.2-Formyl-2'-deoxyadenosine triphosphate (dCHO ATP) was synthesized and tested as a substrate in enzymatic synthesis of DNA modified in the minor groove with a reactive aldehyde group. The multistep synthesis of dCHO ATP was based on the preparation of protected 2-dihydroxyethyl-2'-deoxyadenosine intemediate, which was triphosphorylated and converted to aldehyde through oxidative cleavage. The dCHO ATP triphosphate was a moderate substrate for KOD XL DNA polymerase, and was used for enzymatic synthesis of some sequences using primer extension (PEX). On the other hand, longer sequences (31-mer) with higher number of modifications, or sequences with modifications at adjacent positions did not give full extension. Single-nucleotide extension followed by PEX was used for site-specific incorporation of one aldehyde-linked adenosine into a longer 49-mer sequence. The reactive formyl group was used for cross-linking with peptides and proteins using reductive amination and for fluorescent labelling through oxime formation with an AlexaFluor647-linked hydroxylamine.Klinefelter syndrome (KS; 47,XXY) is the most common sex chromosome abnormality in males (150 per 100,000 males). The condition leads to hypergonadotropic hypogonadism and ever since the condition was described approximately 80 years ago, testosterone treatment has been the cornerstone in care for individuals with KS. However, KS is associated with an array of health-related and socioeconomic challenges and it is becoming progressively clear that proper care for boys and men with KS reaches far beyond simply supplementing with testosterone. There are no widely implemented guidelines for KS care, and studies investigating crucial aspects of testosterone treatment in individuals with KS, including both beneficial and potentially adverse effects, have only begun to emerge during the last decades. For this descriptive review, we present an overview of literature describing health-related outcomes of testosterone treatment in KS and outline the clinical applications of testosterone treatment in KS. Collectively, beneficial effects of testosterone treatment on overall health in KS are described with few apparent adverse effects.
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  • Purpose Diffuse cortical damage in relapsing-remitting multiple sclerosis (RRMS) is clinically relevant but cannot be directly assessed with conventional MRI. In this study, it was aimed to use diffusion tensor imaging (DTI) techniques with optimized intrinsic eddy current compensation to quantify and characterize cortical mean diffusivity (MD) and fractional anisotropy (FA) changes in RRMS and to analyze the distribution of these changes across the cortex. Materials and Methods Three-Tesla MRI acquisition, mapping of the MD providing information about the integrity of microstructural barriers and of the FA reflecting axonal density and surface-based analysis with Freesurfer were performed for 24 RRMS patients and 25 control subjects. Results Across the whole cortex, MD was increased in patients (p less then 0.001), while surface-based analysis revealed focal cortical FA decreases. MD and FA changes were distributed inhomogeneously across the cortex, the MD increase being more widespread than the FA decrease. Cortical MD correlated with the Expanded Disability Status Scale (EDSS, r = 0.38, p = 0.03). Conclusion Damage of microstructural barriers occurs inhomogeneously across the cortex in RRMS and might be spatially more widespread than axonal degeneration. The results and, in particular, the correlation with the clinical status indicate that DTI might be a promising technique for the monitoring of cortical damage under treatment in larger clinical studies. Copyright © 2020 Stock, Shrestha, Seiler, Foerch, Hattingen, Steinmetz, Deichmann, Wagner and Gracien.Introduction Obstructive sleep apnea (OSA) has been associated with non-dipping blood pressure (BP). The precise mechanism is still under investigation, but repetitive oxygen desaturation and arousal induced sleep fragmentation are considered the main contributors. Methods We analyzed beat-to-beat measurements of hemodynamic parameters (HPs) during a 25-min period of wake-sleep transition. Differences in the mean HP values for heart rate (HR), systolic BP (SBP), and stroke volume (SV) during wake and sleep and their standard deviations (SDs) were compared between 34 controls (C) and 22 OSA patients. The Student's t-test for independent samples and the effect size by Cohen's d (d) were calculated. HP evolution was investigated by plotting the measured HP values against each consecutive pulse wave. After a simple regression analysis, the calculated coefficient beta (SCB) was used to indicate the HP evolution. We furthermore explored by a hierarchical block regression which variables increased the prediction forhat the addition of the AI to BMI, age, and AHI increases the prediction of the HP evolution following sleep onset for both SBP and SV and may be the most important variable. Copyright © 2020 Staats, Barros, Fernandes, Grencho, Reis, Matos, Valença, Marôco, de Almeida and Bárbara.Roylea cinerea (D. Don) Baill. (Lamiaceae) is an indigenous plant of Western Himalayas, and has been used by the native population for the treatment of various diseases such as fever, malaria, diabetes, jaundice, and skin ailments. However, limited proportion of pharmacological and toxicological information is available on the bioactive properties of this plant. Therefore, the present study was designed to explore the anti-oxidant and anti-proliferative activities of Roylea cinerea. Methanolic extracts of leaves and stem of Roylea cinerea were prepared through maceration procedure and evaluated for the antioxidant activity using hydrogen/electron donating and hydroxyl radical scavenging assay. Significant antioxidant activity was observed for the methanolic extract of leaves in DPPH (EC50 239 µg/ml), molybdate ion reduction assay (29.73 µg ascorbic acid equivalent/mg dry weight of extract) as well as in plasmid nicking assay. Anti-proliferative and apoptotic activity in L6 rat skeletal muscle cell line was done using in vitro assays, i.e., MTT, Lactate dehydrogenase, mitochondrial membrane potential assay along with phase contrast, confocal, and scanning electron microscopy. The methanol extract of leaves and stem inhibited the growth of L6 cells with IC50 value of 69.41µg/ml and 124.93 µg/ml, respectively, and the lactate dehydrogenase activity was 20.29% and 0.3%, respectively. Cell cycle analysis by flow cytometry exhibited the arrest of cells in G1 and sub-G1 phase by methanolic leaves extract. Furthermore, the results of microscopic and docking analysis strengthened the observation made in the present study regarding the apoptotic mode of cell death in the L6 cell line. The in vitro findings of our studies revealed that the bioactive ingredients present in the methanolic extract of leaves and stem of Roylea cinerea have the anticancer potential. Further in vivo studies are needed to verify the in vitro results. Copyright © 2020 Bhatia, Singh Buttar, Arora, Singh, Singh, Kaur and Arora.Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), is a hereditary small-vessels angiopathy caused by mutations in the NOTCH 3 gene, located on chromosome 19, usually affecting middle-ages adults, whose clinical manifestations include migraine with aura, recurrent strokes, mood disorders, and cognitive impairment leading to dementia and disability. In this review, we provide an overview of the current knowledge on the pathogenic mechanisms underlying the disease, focus on the corresponding therapeutic targets, and discuss the most promising treatment strategies currently under investigations. The hypothesis that CADASIL is an appropriate model to explore the pathogenesis of sporadic cerebral small vessel disease is also reviewed. Copyright © 2020 Locatelli, Padovani and Pezzini.Apelin, an endogenous neuropeptide, has been identified as the cognate ligand for the G-protein-coupled receptor APJ. Apelin, APJ messenger RNA, and protein are widely expressed in the central nervous system and peripheral tissues of humans and animals. The apelin/APJ system has been implicated in diverse physiological and pathological processes. The present article reviews the progress of the latest research investigating the apelin/APJ system in pain, depression, anxiety, memory, epilepsy, neuroprotection, stroke, and brain injury and protection, and highlights its promising potential as a therapeutic target for treatment of psychosis and neuropathy. https://www.selleckchem.com/products/Dexamethasone.html Copyright © 2020 Lv, Chen and Wang.
    Purpose Diffuse cortical damage in relapsing-remitting multiple sclerosis (RRMS) is clinically relevant but cannot be directly assessed with conventional MRI. In this study, it was aimed to use diffusion tensor imaging (DTI) techniques with optimized intrinsic eddy current compensation to quantify and characterize cortical mean diffusivity (MD) and fractional anisotropy (FA) changes in RRMS and to analyze the distribution of these changes across the cortex. Materials and Methods Three-Tesla MRI acquisition, mapping of the MD providing information about the integrity of microstructural barriers and of the FA reflecting axonal density and surface-based analysis with Freesurfer were performed for 24 RRMS patients and 25 control subjects. Results Across the whole cortex, MD was increased in patients (p less then 0.001), while surface-based analysis revealed focal cortical FA decreases. MD and FA changes were distributed inhomogeneously across the cortex, the MD increase being more widespread than the FA decrease. Cortical MD correlated with the Expanded Disability Status Scale (EDSS, r = 0.38, p = 0.03). Conclusion Damage of microstructural barriers occurs inhomogeneously across the cortex in RRMS and might be spatially more widespread than axonal degeneration. The results and, in particular, the correlation with the clinical status indicate that DTI might be a promising technique for the monitoring of cortical damage under treatment in larger clinical studies. Copyright © 2020 Stock, Shrestha, Seiler, Foerch, Hattingen, Steinmetz, Deichmann, Wagner and Gracien.Introduction Obstructive sleep apnea (OSA) has been associated with non-dipping blood pressure (BP). The precise mechanism is still under investigation, but repetitive oxygen desaturation and arousal induced sleep fragmentation are considered the main contributors. Methods We analyzed beat-to-beat measurements of hemodynamic parameters (HPs) during a 25-min period of wake-sleep transition. Differences in the mean HP values for heart rate (HR), systolic BP (SBP), and stroke volume (SV) during wake and sleep and their standard deviations (SDs) were compared between 34 controls (C) and 22 OSA patients. The Student's t-test for independent samples and the effect size by Cohen's d (d) were calculated. HP evolution was investigated by plotting the measured HP values against each consecutive pulse wave. After a simple regression analysis, the calculated coefficient beta (SCB) was used to indicate the HP evolution. We furthermore explored by a hierarchical block regression which variables increased the prediction forhat the addition of the AI to BMI, age, and AHI increases the prediction of the HP evolution following sleep onset for both SBP and SV and may be the most important variable. Copyright © 2020 Staats, Barros, Fernandes, Grencho, Reis, Matos, Valença, Marôco, de Almeida and Bárbara.Roylea cinerea (D. Don) Baill. (Lamiaceae) is an indigenous plant of Western Himalayas, and has been used by the native population for the treatment of various diseases such as fever, malaria, diabetes, jaundice, and skin ailments. However, limited proportion of pharmacological and toxicological information is available on the bioactive properties of this plant. Therefore, the present study was designed to explore the anti-oxidant and anti-proliferative activities of Roylea cinerea. Methanolic extracts of leaves and stem of Roylea cinerea were prepared through maceration procedure and evaluated for the antioxidant activity using hydrogen/electron donating and hydroxyl radical scavenging assay. Significant antioxidant activity was observed for the methanolic extract of leaves in DPPH (EC50 239 µg/ml), molybdate ion reduction assay (29.73 µg ascorbic acid equivalent/mg dry weight of extract) as well as in plasmid nicking assay. Anti-proliferative and apoptotic activity in L6 rat skeletal muscle cell line was done using in vitro assays, i.e., MTT, Lactate dehydrogenase, mitochondrial membrane potential assay along with phase contrast, confocal, and scanning electron microscopy. The methanol extract of leaves and stem inhibited the growth of L6 cells with IC50 value of 69.41µg/ml and 124.93 µg/ml, respectively, and the lactate dehydrogenase activity was 20.29% and 0.3%, respectively. Cell cycle analysis by flow cytometry exhibited the arrest of cells in G1 and sub-G1 phase by methanolic leaves extract. Furthermore, the results of microscopic and docking analysis strengthened the observation made in the present study regarding the apoptotic mode of cell death in the L6 cell line. The in vitro findings of our studies revealed that the bioactive ingredients present in the methanolic extract of leaves and stem of Roylea cinerea have the anticancer potential. Further in vivo studies are needed to verify the in vitro results. Copyright © 2020 Bhatia, Singh Buttar, Arora, Singh, Singh, Kaur and Arora.Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), is a hereditary small-vessels angiopathy caused by mutations in the NOTCH 3 gene, located on chromosome 19, usually affecting middle-ages adults, whose clinical manifestations include migraine with aura, recurrent strokes, mood disorders, and cognitive impairment leading to dementia and disability. In this review, we provide an overview of the current knowledge on the pathogenic mechanisms underlying the disease, focus on the corresponding therapeutic targets, and discuss the most promising treatment strategies currently under investigations. The hypothesis that CADASIL is an appropriate model to explore the pathogenesis of sporadic cerebral small vessel disease is also reviewed. Copyright © 2020 Locatelli, Padovani and Pezzini.Apelin, an endogenous neuropeptide, has been identified as the cognate ligand for the G-protein-coupled receptor APJ. Apelin, APJ messenger RNA, and protein are widely expressed in the central nervous system and peripheral tissues of humans and animals. The apelin/APJ system has been implicated in diverse physiological and pathological processes. The present article reviews the progress of the latest research investigating the apelin/APJ system in pain, depression, anxiety, memory, epilepsy, neuroprotection, stroke, and brain injury and protection, and highlights its promising potential as a therapeutic target for treatment of psychosis and neuropathy. https://www.selleckchem.com/products/Dexamethasone.html Copyright © 2020 Lv, Chen and Wang.
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  • Entwickelte ein Patient klinische Anzeichen einer Infektion wurden erneut Abstriche auf MRE entnommen. Ergebnisse Insgesamt gab es im Studienzeitraum 198 Aufnahmen von 118 unterschiedlichen Patienten auf die Kinderpalliativstation. 18% der Patienten waren mit einem MRE besiedelt. Am häufigsten traten E. coli (8.1%) und Pseudomonas ssp. (8.1%) auf. Bei 58% der Patienten mit einem Tracheostoma konnte ein MRE im Trachealsekret nachgewiesen werden. Die Inzidenzdichte der NI lag bei 0,99 pro 1000 Patiententage. Es trat keine NI durch einen MRE auf. Schlussfolgerung Die hohe Anzahl an MRE besiedelten Patienten auf der Kinderpalliativstation spricht dafür, pädiatrische Palliativpatienten vor einem stationären Aufenthalt auf MRE zu screenen. Besonders sind dabei die Patienten mit einem Tracheostoma zu beachten. Unsere Ergebnisse geben erste Hinweise darauf, dass soziale Teilhabe auf der pädiatrischen Palliativstation für Patienten mit MRE Besiedlung sicher ist, wenn entsprechende Hygienekonzepte angewandt werden.Objective Patients with hereditary bleeding disorders rarely present with intraocular or orbital hemorrhage as the initial symptom. The presence of such a condition can be easily overlooked when contemplating ophthalmic surgery, and can give rise to intraoperative and postoperative complications. Awareness of such conditions can improve surgical decisions. Methods This is a case report of an eight-year-old Filipino male who sustained blunt trauma to his right eye, causing traumatic total hyphema with corneal staining. Subretinal hemorrhage was seen on ultrasound. The patient underwent anterior chamber washout with temporary keratoprosthesis and pars plana vitrectomy with silicone oil tamponade. Clearance of the hyphema was noted postoperatively. However, on follow-up after 19 days, the patient presented with recurrence of hyphema, new onset proptosis and peribulbar hemorrhage. Results Imaging of the orbit revealed new-onset pseudoproptosis with intraocular and peribulbar hemorrhage. https://www.selleckchem.com/products/Imatinib-Mesylate.html A bleeding disorder was suspected at this point. Further probing revealed a family history of prolonged bleeding time in an X-linked genetic inheritance pattern spanning three generations. Laboratory testing of prothrombin, partial thromboplastin, and factor assays were done, which revealed factor VIII deficiency, diagnostic of hemophilia A. No further surgery was done. The patient was given transfusions of fresh frozen plasma, which resolved the hemorrhage. Conclusions Bleeding disorders present a dilemma in the surgical management of patients. In cases of traumatic hemorrhage, adequate history and physical examination should always be done to rule these out. Surgical outcomes in hemophiliacs can be improved with preoperative prophylactic treatment and close postoperative monitoring and care. Copyright © 2020 Aquino et al.A nine-month-old female baby with normal birth history presented with her mother complaining of a white spot in the baby's right eye, which the mother had noticed at five months of age. External photograph showed a retrolental fibroplastic membrane visible in the superior half of the dilated pupil. Retcam fundus photo revealed myelinated nerve fibers extending from the disc till the ora superiorly and forming a membranous fold. Intraoperative OCT confirmed thickened RNFL with compact retina. Thus, the retrolental fibroplasia turned out to be a masquerade for myelinated nerve fibers. Since it was not involving the visual axis with no coexisting traction, the mother was reassured regarding the benign nature of the condition. Copyright © 2020 Sen et al.Objective To report a case of unintentional retina artery amputation during macular peeling. Methods Observational case report Results A 73-year-old female underwent surgery to treat epiretinal membrane (ERM) associated with severe staphyloma in her left eye. While the ERM/posterior hyaloid membrane visually enhanced with triamcinolone (TA) was peeled, a movement of the forceps unintentionally involved the inferior temporal branch artery near the inner edge of the staphyloma. The artery was avulsed and amputated. Oozing from the retinal cleft that had once enfolded the artery and microscopic bleeding from the amputation stump were observed. The vitreous hemorrhage obscured a view of the fundus more than 4 weeks after the surgery. After 8 weeks, postoperative visual acuity was improved; however, the superior nasal visual field was lost, and the patient was aware of the broken vessel as a floater in her vision. Conclusions Macular peeling is technically challenging, so meticulous attention must be paid to avoid any damage on vessels. The retina tissue was stretched in a staphyloma and vessels were bulged into the vitreous space especially at the inner edge of the staphyloma. High levels of TA dye here buried the texture of the retina. Excessive TA should be removed prior to macular peeling. Copyright © 2020 Shimada.Purpose To present an extremely rare case of corneal melanoma. Method An 84-year-old female patient presented to our department with a pigmented corneal lesion in her right eye (OD), 6x4 mm, complaining of mild pain and inability of complete eyelid closure. Tumor growth had been noted the previous year. She had undergone cataract surgery in her right eye three years before, followed by an unspecified postoperative complication. Her visual acuity was 3/10 OD and 9/10 OS. Ophthalmic evaluation and ultrasonography (A- and B-scan) did not reveal any other pathology. The pigmented lesion was surgically removed and the patient underwent a protocol therapy of topical chemotherapy (mitomycin 0.03%, 2x4 for 2 weeks and dexamethasone 0.1%, 2x4 for the following 2 weeks, followed by another cycle of mitomycin 0.03%, 2x4 for another 2 weeks). Results The surgical removal of the lesion was uncomplicated, as was the postoperative period. The patient's visual acuity improved to 6/10 three months postoperatively. The histologic examination revealed malignant melanoma. Conclusions Despite its rarity, primary melanoma of the cornea is an existing entity. Treatment of corneal melanoma consists of surgical removal and postoperative topical chemotherapy. Postoperative follow-up is mandatory. Copyright © 2020 Panagiotou et al.
    Entwickelte ein Patient klinische Anzeichen einer Infektion wurden erneut Abstriche auf MRE entnommen. Ergebnisse Insgesamt gab es im Studienzeitraum 198 Aufnahmen von 118 unterschiedlichen Patienten auf die Kinderpalliativstation. 18% der Patienten waren mit einem MRE besiedelt. Am häufigsten traten E. coli (8.1%) und Pseudomonas ssp. (8.1%) auf. Bei 58% der Patienten mit einem Tracheostoma konnte ein MRE im Trachealsekret nachgewiesen werden. Die Inzidenzdichte der NI lag bei 0,99 pro 1000 Patiententage. Es trat keine NI durch einen MRE auf. Schlussfolgerung Die hohe Anzahl an MRE besiedelten Patienten auf der Kinderpalliativstation spricht dafür, pädiatrische Palliativpatienten vor einem stationären Aufenthalt auf MRE zu screenen. Besonders sind dabei die Patienten mit einem Tracheostoma zu beachten. Unsere Ergebnisse geben erste Hinweise darauf, dass soziale Teilhabe auf der pädiatrischen Palliativstation für Patienten mit MRE Besiedlung sicher ist, wenn entsprechende Hygienekonzepte angewandt werden.Objective Patients with hereditary bleeding disorders rarely present with intraocular or orbital hemorrhage as the initial symptom. The presence of such a condition can be easily overlooked when contemplating ophthalmic surgery, and can give rise to intraoperative and postoperative complications. Awareness of such conditions can improve surgical decisions. Methods This is a case report of an eight-year-old Filipino male who sustained blunt trauma to his right eye, causing traumatic total hyphema with corneal staining. Subretinal hemorrhage was seen on ultrasound. The patient underwent anterior chamber washout with temporary keratoprosthesis and pars plana vitrectomy with silicone oil tamponade. Clearance of the hyphema was noted postoperatively. However, on follow-up after 19 days, the patient presented with recurrence of hyphema, new onset proptosis and peribulbar hemorrhage. Results Imaging of the orbit revealed new-onset pseudoproptosis with intraocular and peribulbar hemorrhage. https://www.selleckchem.com/products/Imatinib-Mesylate.html A bleeding disorder was suspected at this point. Further probing revealed a family history of prolonged bleeding time in an X-linked genetic inheritance pattern spanning three generations. Laboratory testing of prothrombin, partial thromboplastin, and factor assays were done, which revealed factor VIII deficiency, diagnostic of hemophilia A. No further surgery was done. The patient was given transfusions of fresh frozen plasma, which resolved the hemorrhage. Conclusions Bleeding disorders present a dilemma in the surgical management of patients. In cases of traumatic hemorrhage, adequate history and physical examination should always be done to rule these out. Surgical outcomes in hemophiliacs can be improved with preoperative prophylactic treatment and close postoperative monitoring and care. Copyright © 2020 Aquino et al.A nine-month-old female baby with normal birth history presented with her mother complaining of a white spot in the baby's right eye, which the mother had noticed at five months of age. External photograph showed a retrolental fibroplastic membrane visible in the superior half of the dilated pupil. Retcam fundus photo revealed myelinated nerve fibers extending from the disc till the ora superiorly and forming a membranous fold. Intraoperative OCT confirmed thickened RNFL with compact retina. Thus, the retrolental fibroplasia turned out to be a masquerade for myelinated nerve fibers. Since it was not involving the visual axis with no coexisting traction, the mother was reassured regarding the benign nature of the condition. Copyright © 2020 Sen et al.Objective To report a case of unintentional retina artery amputation during macular peeling. Methods Observational case report Results A 73-year-old female underwent surgery to treat epiretinal membrane (ERM) associated with severe staphyloma in her left eye. While the ERM/posterior hyaloid membrane visually enhanced with triamcinolone (TA) was peeled, a movement of the forceps unintentionally involved the inferior temporal branch artery near the inner edge of the staphyloma. The artery was avulsed and amputated. Oozing from the retinal cleft that had once enfolded the artery and microscopic bleeding from the amputation stump were observed. The vitreous hemorrhage obscured a view of the fundus more than 4 weeks after the surgery. After 8 weeks, postoperative visual acuity was improved; however, the superior nasal visual field was lost, and the patient was aware of the broken vessel as a floater in her vision. Conclusions Macular peeling is technically challenging, so meticulous attention must be paid to avoid any damage on vessels. The retina tissue was stretched in a staphyloma and vessels were bulged into the vitreous space especially at the inner edge of the staphyloma. High levels of TA dye here buried the texture of the retina. Excessive TA should be removed prior to macular peeling. Copyright © 2020 Shimada.Purpose To present an extremely rare case of corneal melanoma. Method An 84-year-old female patient presented to our department with a pigmented corneal lesion in her right eye (OD), 6x4 mm, complaining of mild pain and inability of complete eyelid closure. Tumor growth had been noted the previous year. She had undergone cataract surgery in her right eye three years before, followed by an unspecified postoperative complication. Her visual acuity was 3/10 OD and 9/10 OS. Ophthalmic evaluation and ultrasonography (A- and B-scan) did not reveal any other pathology. The pigmented lesion was surgically removed and the patient underwent a protocol therapy of topical chemotherapy (mitomycin 0.03%, 2x4 for 2 weeks and dexamethasone 0.1%, 2x4 for the following 2 weeks, followed by another cycle of mitomycin 0.03%, 2x4 for another 2 weeks). Results The surgical removal of the lesion was uncomplicated, as was the postoperative period. The patient's visual acuity improved to 6/10 three months postoperatively. The histologic examination revealed malignant melanoma. Conclusions Despite its rarity, primary melanoma of the cornea is an existing entity. Treatment of corneal melanoma consists of surgical removal and postoperative topical chemotherapy. Postoperative follow-up is mandatory. Copyright © 2020 Panagiotou et al.
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