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  • 001) and 1.65 (95% CI, 1.18 to 2.28; p = 0.006) respectively, relative to AA homozygote. For the HHEX variant rs1111875 (T/C), heterozygous and homozygous carriers for allele 'C' have odds ratios of 1.13 (95% CI, 0.91 to 1.42; p = 0.27) and 1.58 (95% CI, 1.17 to 2.12; p = 0.003) respectively, relative to the TT homozygote. For CDKN2A/2B variant rs7020996, the heterozygous and homozygous carriers of allele 'C' were protective with odds ratios of 0.65 (95% CI, 0.51 to 0.83; p = 0.0004) and 0.62 (95% CI, 0.27 to 1.39; p = 0.24) respectively, relative to TT homozygote. This is the first study to report on the association of HHEX variant rs1111875 with EOT2D in this population.Single-cell RNA sequencing (scRNA-seq) has been widely applied to provide insights into the cell-by-cell expression difference in a given bulk sample. Accordingly, numerous analysis methods have been developed. As it involves simultaneous analyses of many cell and genes, efficiency of the methods is crucial. https://www.selleckchem.com/products/nvl-655.html The conventional cell type annotation method is laborious and subjective. Here we propose a semi-automatic method that calculates a normalized score for each cell type based on user-supplied cell type-specific marker gene list. The method was applied to a publicly available scRNA-seq data of mouse cardiac non-myocyte cell pool. Annotating the 35 t-stochastic neighbor embedding clusters into 12 cell types was straightforward, and its accuracy was evaluated by constructing co-expression network for each cell type. Gene Ontology analysis was congruent with the annotated cell type and the corollary regulatory network analysis showed upstream transcription factors that have well supported literature evidences. The source code is available as an R script upon request.
    Medullary thyroid carcinoma (MTC) is an aggressive malignancy originating from the parafollicular C cells. Preoperatively, thyroid nodule fine-needle aspiration cytology (FNAC) and pathogenic gene mutations are definitive in approximately one-half of cases. MicroRNAs (miRNAs) are endogenous, noncoding, single-stranded RNAs that regulate gene expression, a characteristic that confers the potential for identifying malignancy. In the current study, the authors hypothesized that differential pairwise (diff-pair) analysis of miRNA expression levels would reliably identify ****in FNA samples.

    The relative abundance of 10 different miRNAs in total nucleic acids was obtained from ThyraMIR test results. Diff-pair analysis was performed by subtracting the critical threshold value of one miRNA from the critical threshold values of other miRNAs. Next-generation sequencing with the ThyGeNEXT panel identified oncogenic gene alterations. The discovery cohort consisted of 30 formalin-fixed, paraffin-embedded benign and mte FNAC findings.
    This study was designed to test the hypothesis that the effectiveness of intensive treatment for locoregionally advanced head and neck cancer (LAHNC) depends on the proportion of patients' overall event risk attributable to cancer.

    This study analyzed 22,339 patients with LAHNC treated in 81 randomized trials testing altered fractionation (AFX; Meta-Analysis of Radiotherapy in Squamous Cell Carcinomas of Head and Neck [MARCH] data set) or chemotherapy (Meta-Analysis of Chemotherapy in Head and Neck Cancer [****-NC] data set). Generalized competing event regression was applied to the control arms in MARCH, and patients were stratified by tertile according to the ω score, which quantified the relative hazard for cancer versus competing events. The classifier was externally validated on the ****-NC data set. The study tested for interactions between the ω score and treatment effects on overall survival (OS).

    Factors associated with a higher ω score were a younger age, a better performance status, an oral cavity site, higher T and N categories, and a p16-negative/unknown status. The effect of AFX on OS was greater in patients with high ω scores (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.85-0.99) and medium ω scores (HR, 0.91; 95% CI, 0.84-0.98) versus low ω scores (HR, 0.97; 95% CI, 0.90-1.05; P for interaction = .086). The effect of chemotherapy on OS was significantly greater in patients with high ω scores (HR, 0.81; 95% CI, 0.75-0.88) and medium ω scores (HR, 0.86; 95% CI, 0.78-0.93) versus low ω scores (HR, 0.96; 95% CI, 0.86-1.08; P for interaction = .011).

    LAHNC patients with a higher risk of cancer progression relative to competing mortality, as reflected by a higher ω score, selectively benefit from more intensive treatment.
    LAHNC patients with a higher risk of cancer progression relative to competing mortality, as reflected by a higher ω score, selectively benefit from more intensive treatment.
    Many group-living primate species have evolved the capacity for some individuals to live alone for part of their lives, but this solitary life stage has rarely been the subject of focused research. The mantled howler monkey (Alouatta palliata) is a social primate species with bisexual dispersal that lives in mixed-sex groups with low male-to-female sex ratios. Consequently, males often spend a long period of their lives as solitary individuals. This study compares the tree use, feeding, and long-distance vocalization behavior of solitary and group-living mantled howler monkey males living within a fragmented rainforest in Costa Rica, La Suerte Biological Research Station. Based on differences in competitive ability between solitary and group-living males, we predicted that lone males would be found in significantly smaller feeding and resting trees, consume more low-quality foods, and produce shorter howling bouts made at lower rates than group-living males.

    We collected data on tree use and feeding during 30-min focal samples on male focal animals, recording data at 2-min intervals. We measured the trees in which the monkeys fed and rested for two or more intervals, and recorded the plant parts consumed. We recorded howling behavior using all-occurrences sampling.

    Lone males used significantly smaller feeding and resting trees, consumed more low-quality foods, and howled at lower rates but had longer howling bouts triggered by anthropogenic noise more than group-living males.

    Our results demonstrate that lone males differ in their behavioral ecology compared to group-living males, thus improving understanding of the solitary male life stage in primates.
    Our results demonstrate that lone males differ in their behavioral ecology compared to group-living males, thus improving understanding of the solitary male life stage in primates.
    001) and 1.65 (95% CI, 1.18 to 2.28; p = 0.006) respectively, relative to AA homozygote. For the HHEX variant rs1111875 (T/C), heterozygous and homozygous carriers for allele 'C' have odds ratios of 1.13 (95% CI, 0.91 to 1.42; p = 0.27) and 1.58 (95% CI, 1.17 to 2.12; p = 0.003) respectively, relative to the TT homozygote. For CDKN2A/2B variant rs7020996, the heterozygous and homozygous carriers of allele 'C' were protective with odds ratios of 0.65 (95% CI, 0.51 to 0.83; p = 0.0004) and 0.62 (95% CI, 0.27 to 1.39; p = 0.24) respectively, relative to TT homozygote. This is the first study to report on the association of HHEX variant rs1111875 with EOT2D in this population.Single-cell RNA sequencing (scRNA-seq) has been widely applied to provide insights into the cell-by-cell expression difference in a given bulk sample. Accordingly, numerous analysis methods have been developed. As it involves simultaneous analyses of many cell and genes, efficiency of the methods is crucial. https://www.selleckchem.com/products/nvl-655.html The conventional cell type annotation method is laborious and subjective. Here we propose a semi-automatic method that calculates a normalized score for each cell type based on user-supplied cell type-specific marker gene list. The method was applied to a publicly available scRNA-seq data of mouse cardiac non-myocyte cell pool. Annotating the 35 t-stochastic neighbor embedding clusters into 12 cell types was straightforward, and its accuracy was evaluated by constructing co-expression network for each cell type. Gene Ontology analysis was congruent with the annotated cell type and the corollary regulatory network analysis showed upstream transcription factors that have well supported literature evidences. The source code is available as an R script upon request. Medullary thyroid carcinoma (MTC) is an aggressive malignancy originating from the parafollicular C cells. Preoperatively, thyroid nodule fine-needle aspiration cytology (FNAC) and pathogenic gene mutations are definitive in approximately one-half of cases. MicroRNAs (miRNAs) are endogenous, noncoding, single-stranded RNAs that regulate gene expression, a characteristic that confers the potential for identifying malignancy. In the current study, the authors hypothesized that differential pairwise (diff-pair) analysis of miRNA expression levels would reliably identify MTC in FNA samples. The relative abundance of 10 different miRNAs in total nucleic acids was obtained from ThyraMIR test results. Diff-pair analysis was performed by subtracting the critical threshold value of one miRNA from the critical threshold values of other miRNAs. Next-generation sequencing with the ThyGeNEXT panel identified oncogenic gene alterations. The discovery cohort consisted of 30 formalin-fixed, paraffin-embedded benign and mte FNAC findings. This study was designed to test the hypothesis that the effectiveness of intensive treatment for locoregionally advanced head and neck cancer (LAHNC) depends on the proportion of patients' overall event risk attributable to cancer. This study analyzed 22,339 patients with LAHNC treated in 81 randomized trials testing altered fractionation (AFX; Meta-Analysis of Radiotherapy in Squamous Cell Carcinomas of Head and Neck [MARCH] data set) or chemotherapy (Meta-Analysis of Chemotherapy in Head and Neck Cancer [MACH-NC] data set). Generalized competing event regression was applied to the control arms in MARCH, and patients were stratified by tertile according to the ω score, which quantified the relative hazard for cancer versus competing events. The classifier was externally validated on the MACH-NC data set. The study tested for interactions between the ω score and treatment effects on overall survival (OS). Factors associated with a higher ω score were a younger age, a better performance status, an oral cavity site, higher T and N categories, and a p16-negative/unknown status. The effect of AFX on OS was greater in patients with high ω scores (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.85-0.99) and medium ω scores (HR, 0.91; 95% CI, 0.84-0.98) versus low ω scores (HR, 0.97; 95% CI, 0.90-1.05; P for interaction = .086). The effect of chemotherapy on OS was significantly greater in patients with high ω scores (HR, 0.81; 95% CI, 0.75-0.88) and medium ω scores (HR, 0.86; 95% CI, 0.78-0.93) versus low ω scores (HR, 0.96; 95% CI, 0.86-1.08; P for interaction = .011). LAHNC patients with a higher risk of cancer progression relative to competing mortality, as reflected by a higher ω score, selectively benefit from more intensive treatment. LAHNC patients with a higher risk of cancer progression relative to competing mortality, as reflected by a higher ω score, selectively benefit from more intensive treatment. Many group-living primate species have evolved the capacity for some individuals to live alone for part of their lives, but this solitary life stage has rarely been the subject of focused research. The mantled howler monkey (Alouatta palliata) is a social primate species with bisexual dispersal that lives in mixed-sex groups with low male-to-female sex ratios. Consequently, males often spend a long period of their lives as solitary individuals. This study compares the tree use, feeding, and long-distance vocalization behavior of solitary and group-living mantled howler monkey males living within a fragmented rainforest in Costa Rica, La Suerte Biological Research Station. Based on differences in competitive ability between solitary and group-living males, we predicted that lone males would be found in significantly smaller feeding and resting trees, consume more low-quality foods, and produce shorter howling bouts made at lower rates than group-living males. We collected data on tree use and feeding during 30-min focal samples on male focal animals, recording data at 2-min intervals. We measured the trees in which the monkeys fed and rested for two or more intervals, and recorded the plant parts consumed. We recorded howling behavior using all-occurrences sampling. Lone males used significantly smaller feeding and resting trees, consumed more low-quality foods, and howled at lower rates but had longer howling bouts triggered by anthropogenic noise more than group-living males. Our results demonstrate that lone males differ in their behavioral ecology compared to group-living males, thus improving understanding of the solitary male life stage in primates. Our results demonstrate that lone males differ in their behavioral ecology compared to group-living males, thus improving understanding of the solitary male life stage in primates.
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  • Meanwhile, since there is no ground truth for the feature maps generated by the AD-LSTM, we propose an adversarial learning algorithm to optimize the AD-LSTM. With the help of adversarial learning, the Siamese network can generate the response maps more accurately, and the AD-LSTM can generate the feature maps of the target more robustly. The experimental results show that our tracker performs favorably against the state-of-the-art trackers on six challenging benchmarks OTB-100, TC-128, VOT2016, VOT2017, GOT-10k, and TrackingNet.Understanding correlation judgement is important to designing effective visualizations of bivariate data. Prior work on correlation perception has not considered how factors including prior beliefs and uncertainty representation impact such judgements. The present work focuses on the impact of uncertainty communication when judging bivariate visualizations. Specifically, we model how users update their beliefs about variable relationships after seeing a scatterplot with and without uncertainty representation. To model and evaluate the belief updating, we present three studies. Study 1 focuses on a proposed "Line + Cone" visual elicitation method for capturing users' beliefs in an accurate and intuitive fashion. The findings reveal that our proposed method of belief solicitation reduces complexity and accurately captures the users' uncertainty about a range of bivariate relationships. Study 2 leverages the "Line + Cone" elicitation method to measure belief updating on the relationship between different sets of variables when seeing correlation visualization with and without uncertainty representation. We compare changes in users beliefs to the predictions of Bayesian cognitive models which provide normative benchmarks for how users should update their prior beliefs about a relationship in light of observed data. The findings from Study 2 revealed that one of the visualization conditions with uncertainty communication led to users being slightly more confident about their judgement compared to visualization without uncertainty information. https://www.selleckchem.com/products/art26-12.html Study 3 builds on findings from Study 2 and explores differences in belief update when the bivariate visualization is congruent or incongruent with users' prior belief. Our results highlight the effects of incorporating uncertainty representation, and the potential of measuring belief updating on correlation judgement with Bayesian cognitive models.Synthesizing realistic 3D mesh deformation sequences is a challenging but important task in computer animation. To achieve this, researchers have long been focusing on shape analysis to develop new interpolation and extrapolation techniques. However, such techniques have limited learning capabilities and therefore often produce unrealistic deformation. Although there are already networks defined on individual meshes, deep architectures that operate directly on mesh sequences with temporal information remain unexplored due to the following major barriers irregular mesh connectivity, rich temporal information, and varied deformation. To address these issues, we utilize convolutional neural networks defined on triangular meshes along with a shape deformation representation to extract useful features, followed by long short-term memory(LSTM) that iteratively processes the features. To fully respect the bidirectional nature of actions, we propose a new share-weight bidirectional scheme to better synthesize deformations. An extensive evaluation shows that our approach outperforms existing methods in sequence generation, both qualitatively and quantitatively.In the last two decades, interactive visualization and analysis have become a central tool in data-driven decision making. Concurrently to the contributions in data visualization, research in data management has produced technology that directly benefits interactive analysis. Here, we contribute a systematic review of 30 years of work in this adjacent field, and highlight techniques and principles we believe to be underappreciated in visualization work. We structure our review along two axes. First, we use task taxonomies from the visualization literature to structure the space of interactions in usual systems. Second, we created a categorization of data management work that strikes a balance between specificity and generality. Concretely, we contribute a characterization of 131 research papers along these two axes. We find that five notions in data management venues fit interactive visualization systems well materialized views, approximate query processing, user modeling and query prediction, muiti-query optimization, lineage techniques, and indexing techniques. In addition, we find a preponderance of work in materialized views and approximate query processing, most targeting a limited subset of the interaction tasks in the taxonomy we used. This suggests natural avenues of future research both in visualization and data management. Our categorization both changes how we visualization researchers design and build our systems, and highlights where future work is necessary.How do analysts think about grouping and spatial operations? This overarching research question incorporates a number of points for investigation, including understanding how analysts begin to explore a dataset, the types of grouping/spatial structures created and the operations performed on them, the relationship between grouping and spatial structures, the decisions analysts make when exploring individual observations, and the role of external information. This work contributes the design and results of such a study, in which a group of participants are asked to organize the data contained within an unfamiliar quantitative dataset. We identify several overarching approaches taken by participants to design their organizational space, discuss the interactions performed by the participants, and propose design recommendations to improve the usability of future high-dimensional data exploration tools that make use of grouping (clustering) and spatial (dimension reduction) operations.Recently, infrared small target detection problem has attracted substantial attention. Many works based on local low-rank model have been proven to be very successful for enhancing the discriminability during detection. However, these methods construct patches by traversing local images and ignore the correlations among different patches. Although the calculation is simplified, some texture information of the target is ignored, and targets of arbitrary forms cannot be accurately identified. In this paper, a novel target-aware method based on a non-local low-rank model and saliency filter regularization is proposed, with which the newly proposed detection framework can be tailored as a non-convex optimization problem, therein enabling joint target saliency learning in a lower dimensional discriminative manifold. More specifically, non-local patch construction is applied for the proposed target-aware low-rank model. By combining similar patches, we reconstruct them together to achieve a better generalization of non-local spatial sparsity constraints.
    Meanwhile, since there is no ground truth for the feature maps generated by the AD-LSTM, we propose an adversarial learning algorithm to optimize the AD-LSTM. With the help of adversarial learning, the Siamese network can generate the response maps more accurately, and the AD-LSTM can generate the feature maps of the target more robustly. The experimental results show that our tracker performs favorably against the state-of-the-art trackers on six challenging benchmarks OTB-100, TC-128, VOT2016, VOT2017, GOT-10k, and TrackingNet.Understanding correlation judgement is important to designing effective visualizations of bivariate data. Prior work on correlation perception has not considered how factors including prior beliefs and uncertainty representation impact such judgements. The present work focuses on the impact of uncertainty communication when judging bivariate visualizations. Specifically, we model how users update their beliefs about variable relationships after seeing a scatterplot with and without uncertainty representation. To model and evaluate the belief updating, we present three studies. Study 1 focuses on a proposed "Line + Cone" visual elicitation method for capturing users' beliefs in an accurate and intuitive fashion. The findings reveal that our proposed method of belief solicitation reduces complexity and accurately captures the users' uncertainty about a range of bivariate relationships. Study 2 leverages the "Line + Cone" elicitation method to measure belief updating on the relationship between different sets of variables when seeing correlation visualization with and without uncertainty representation. We compare changes in users beliefs to the predictions of Bayesian cognitive models which provide normative benchmarks for how users should update their prior beliefs about a relationship in light of observed data. The findings from Study 2 revealed that one of the visualization conditions with uncertainty communication led to users being slightly more confident about their judgement compared to visualization without uncertainty information. https://www.selleckchem.com/products/art26-12.html Study 3 builds on findings from Study 2 and explores differences in belief update when the bivariate visualization is congruent or incongruent with users' prior belief. Our results highlight the effects of incorporating uncertainty representation, and the potential of measuring belief updating on correlation judgement with Bayesian cognitive models.Synthesizing realistic 3D mesh deformation sequences is a challenging but important task in computer animation. To achieve this, researchers have long been focusing on shape analysis to develop new interpolation and extrapolation techniques. However, such techniques have limited learning capabilities and therefore often produce unrealistic deformation. Although there are already networks defined on individual meshes, deep architectures that operate directly on mesh sequences with temporal information remain unexplored due to the following major barriers irregular mesh connectivity, rich temporal information, and varied deformation. To address these issues, we utilize convolutional neural networks defined on triangular meshes along with a shape deformation representation to extract useful features, followed by long short-term memory(LSTM) that iteratively processes the features. To fully respect the bidirectional nature of actions, we propose a new share-weight bidirectional scheme to better synthesize deformations. An extensive evaluation shows that our approach outperforms existing methods in sequence generation, both qualitatively and quantitatively.In the last two decades, interactive visualization and analysis have become a central tool in data-driven decision making. Concurrently to the contributions in data visualization, research in data management has produced technology that directly benefits interactive analysis. Here, we contribute a systematic review of 30 years of work in this adjacent field, and highlight techniques and principles we believe to be underappreciated in visualization work. We structure our review along two axes. First, we use task taxonomies from the visualization literature to structure the space of interactions in usual systems. Second, we created a categorization of data management work that strikes a balance between specificity and generality. Concretely, we contribute a characterization of 131 research papers along these two axes. We find that five notions in data management venues fit interactive visualization systems well materialized views, approximate query processing, user modeling and query prediction, muiti-query optimization, lineage techniques, and indexing techniques. In addition, we find a preponderance of work in materialized views and approximate query processing, most targeting a limited subset of the interaction tasks in the taxonomy we used. This suggests natural avenues of future research both in visualization and data management. Our categorization both changes how we visualization researchers design and build our systems, and highlights where future work is necessary.How do analysts think about grouping and spatial operations? This overarching research question incorporates a number of points for investigation, including understanding how analysts begin to explore a dataset, the types of grouping/spatial structures created and the operations performed on them, the relationship between grouping and spatial structures, the decisions analysts make when exploring individual observations, and the role of external information. This work contributes the design and results of such a study, in which a group of participants are asked to organize the data contained within an unfamiliar quantitative dataset. We identify several overarching approaches taken by participants to design their organizational space, discuss the interactions performed by the participants, and propose design recommendations to improve the usability of future high-dimensional data exploration tools that make use of grouping (clustering) and spatial (dimension reduction) operations.Recently, infrared small target detection problem has attracted substantial attention. Many works based on local low-rank model have been proven to be very successful for enhancing the discriminability during detection. However, these methods construct patches by traversing local images and ignore the correlations among different patches. Although the calculation is simplified, some texture information of the target is ignored, and targets of arbitrary forms cannot be accurately identified. In this paper, a novel target-aware method based on a non-local low-rank model and saliency filter regularization is proposed, with which the newly proposed detection framework can be tailored as a non-convex optimization problem, therein enabling joint target saliency learning in a lower dimensional discriminative manifold. More specifically, non-local patch construction is applied for the proposed target-aware low-rank model. By combining similar patches, we reconstruct them together to achieve a better generalization of non-local spatial sparsity constraints.
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  • Anterograde interference refers to the negative impact of prior learning on the propensity for future learning. There is currently no consensus on whether this phenomenon is transient or long lasting, with studies pointing to an effect in the time scale of hours to days. These inconsistencies might be caused by the method employed to quantify performance, which often confounds changes in learning rate and retention. Here, we aimed to unveil the time course of anterograde interference by tracking its impact on visuomotor adaptation at different intervals throughout a 24-h period. Our empirical and model-based approaches allowed us to measure the capacity for new learning separately from the influence of a previous memory. In agreement with previous reports, we found that prior learning persistently impaired the initial level of performance upon revisiting the task. However, despite this strong initial bias, learning capacity was impaired only when conflicting information was learned up to 1 h apart, recovering thereafter with passage of time. These findings suggest that when adapting to conflicting perturbations, impairments in performance are driven by two distinct mechanisms a long-lasting bias that acts as a prior and hinders initial performance and a short-lasting anterograde interference that originates from a reduction in error sensitivity. https://www.selleckchem.com/products/gunagratinib.html © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail journals.permission@oup.com.CONTEXT Anabolic hormones are important factors in maintaining muscle mass for ageing men, but their role in overall motor unit structure and function is unclear. OBJECTIVE To determine associations of anabolic and reproductive hormone levels with motor unit characteristics in quadriceps muscle in older healthy and frail men. DESIGN Observational cohort study of community dwelling men. PARTICIPANTS Healthy and frail men > 65 years old. INTERVENTION None. OUTCOME MEASURE Quantitative assessments of electromyography-derived motor unit potential size (MUP) and compound muscle action potential size (CMAP) of vastus lateralis muscle. RESULTS We studied 98 men (mean±SD age 73±6 years; BMI 25.7±4.0 kg/m2; diabetes 11%) of whom 45% were prefrail and 18% frail. After adjusting for age, BMI and prevalent diabetes, higher total and free testosterone levels were significantly related to larger CMAP (total testosterone β (95% CI) 0.3 (0.08, 0.53); free testosterone 0.34 (0.13, 0.56)). Exploratory analysis showed the relationship between free testosterone and CMAP was stronger in frail rather than robust men. In univariate analyses, estradiol was associated with CMAP size (0.37 (0.16, 0.57)); and vitamin D was associated with MUP size (0.22 (0.01, 0.43)) but these relationships were no longer significant after adjusting for potential confounders. CONCLUSION Our data highlight the associations between androgen levels and the electrophysiological characteristics of older men, particularly in the frail. Clinical trials involving administration of androgens will help to elucidate the potential benefits of intervention on neuromuscular function and/or frailty status. © Endocrine Society 2020. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.BACKGROUND Cognitive dysfunction is common in older adults, particularly in those with type 2 diabetes (T2D). Higher adherence to the Dietary Guidelines for Americans is associated with better brain health. However, it is unclear if adherence to the Australian Dietary Guidelines (ADG) is associated with cognition or brain structure in older adults. OBJECTIVE The aims of this study were to 1) examine the relation between adherence to the ADG, cognition, and brain MRI and 2) determine whether T2D modifies any associations. METHODS The Cognition and Diabetes in Older Tasmanians Study is a cross-sectional study in 688 people (n = 343 with T2D) aged 55-90 y. A validated 80-item food-frequency questionnaire was used to assess dietary intake. Adherence to the 2013 ADG was estimated using the Dietary Guidelines Index (DGI). Cognitive function in multiple domains was assessed with a comprehensive battery of neuropsychological tests and brain structure with MRI. Multivariable linear models were used to assess the associations between DGI, cognitive z scores, and brain structure. Effect modification for T2D was examined with a DGI × T2D product term. RESULTS The mean age of the sample was 69.9 y (SD 7.4 y), with 57.1% men. The mean DGI was 54.8 (SD 10.7; range 24.1-84.6). No associations were observed between the Australian DGI and cognition or brain MRI measures. T2D did not modify any associations (P > 0.05). CONCLUSIONS This is the first study to investigate associations between adherence to the ADG and brain health in the older adults with and without T2D. Future prospective studies are required to clarify if there are long-term associations. Copyright © The Author(s) 2020.BACKGROUND With the increasing demand for body contouring procedures in the US over the past two decades, more surgeons with diverse specialty training are performing these procedures. However, little is known regarding the comparative outcomes of these patients. OBJECTIVES The purpose of this study was to compare outcomes of body contouring procedures based on the specialty training of the surgeon. METHODS Data from the American College of Surgeons National Surgical Quality Improvement Program (2005-2015) were reviewed for all body contouring procedures. Patients were stratified by surgeon training (Plastic Surgery [PS] vs. General Surgery [GS]). Descriptive statistics and regression analyses were used to evaluate differences in outcomes. RESULTS A total of 11,658 patients were included; 9,502 PS cases and 2,156 GS cases. Most were women (90.4%), aged 40 to 59 (52.7%) and White (79.5%). Compared to PS patients, GS patients were more likely obese (61.4% vs. 40.6%), smokers (13.6% vs. 9.8%), and with ASA≥3 (35.3% vs. 18.6%) (all P less then 0.001). Abdominal contouring procedures were the most common (76%) cases. Multivariate regression revealed that compared to PS cases, those performed by GS were associated with increased wound and infectious complications (adjusted Odds Ratio, aOR 1.81; 95% Confidence Interval, 95%CI 1.44 - 2.27), reoperation (aOR 1.85; 95%CI 1.31 - 2.62), and predicted mean length of stay (1.12 d; 95%CI 0.64 - 1.60). CONCLUSIONS The variable outcomes in body contouring procedures performed by PS compared to GS may imply procedural-algorithmic differences between the subspecialties leading to the noted outcome differential. © 2020 The Aesthetic Society. Reprints and permission journals.permissions@oup.com.
    Anterograde interference refers to the negative impact of prior learning on the propensity for future learning. There is currently no consensus on whether this phenomenon is transient or long lasting, with studies pointing to an effect in the time scale of hours to days. These inconsistencies might be caused by the method employed to quantify performance, which often confounds changes in learning rate and retention. Here, we aimed to unveil the time course of anterograde interference by tracking its impact on visuomotor adaptation at different intervals throughout a 24-h period. Our empirical and model-based approaches allowed us to measure the capacity for new learning separately from the influence of a previous memory. In agreement with previous reports, we found that prior learning persistently impaired the initial level of performance upon revisiting the task. However, despite this strong initial bias, learning capacity was impaired only when conflicting information was learned up to 1 h apart, recovering thereafter with passage of time. These findings suggest that when adapting to conflicting perturbations, impairments in performance are driven by two distinct mechanisms a long-lasting bias that acts as a prior and hinders initial performance and a short-lasting anterograde interference that originates from a reduction in error sensitivity. https://www.selleckchem.com/products/gunagratinib.html © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail journals.permission@oup.com.CONTEXT Anabolic hormones are important factors in maintaining muscle mass for ageing men, but their role in overall motor unit structure and function is unclear. OBJECTIVE To determine associations of anabolic and reproductive hormone levels with motor unit characteristics in quadriceps muscle in older healthy and frail men. DESIGN Observational cohort study of community dwelling men. PARTICIPANTS Healthy and frail men > 65 years old. INTERVENTION None. OUTCOME MEASURE Quantitative assessments of electromyography-derived motor unit potential size (MUP) and compound muscle action potential size (CMAP) of vastus lateralis muscle. RESULTS We studied 98 men (mean±SD age 73±6 years; BMI 25.7±4.0 kg/m2; diabetes 11%) of whom 45% were prefrail and 18% frail. After adjusting for age, BMI and prevalent diabetes, higher total and free testosterone levels were significantly related to larger CMAP (total testosterone β (95% CI) 0.3 (0.08, 0.53); free testosterone 0.34 (0.13, 0.56)). Exploratory analysis showed the relationship between free testosterone and CMAP was stronger in frail rather than robust men. In univariate analyses, estradiol was associated with CMAP size (0.37 (0.16, 0.57)); and vitamin D was associated with MUP size (0.22 (0.01, 0.43)) but these relationships were no longer significant after adjusting for potential confounders. CONCLUSION Our data highlight the associations between androgen levels and the electrophysiological characteristics of older men, particularly in the frail. Clinical trials involving administration of androgens will help to elucidate the potential benefits of intervention on neuromuscular function and/or frailty status. © Endocrine Society 2020. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.BACKGROUND Cognitive dysfunction is common in older adults, particularly in those with type 2 diabetes (T2D). Higher adherence to the Dietary Guidelines for Americans is associated with better brain health. However, it is unclear if adherence to the Australian Dietary Guidelines (ADG) is associated with cognition or brain structure in older adults. OBJECTIVE The aims of this study were to 1) examine the relation between adherence to the ADG, cognition, and brain MRI and 2) determine whether T2D modifies any associations. METHODS The Cognition and Diabetes in Older Tasmanians Study is a cross-sectional study in 688 people (n = 343 with T2D) aged 55-90 y. A validated 80-item food-frequency questionnaire was used to assess dietary intake. Adherence to the 2013 ADG was estimated using the Dietary Guidelines Index (DGI). Cognitive function in multiple domains was assessed with a comprehensive battery of neuropsychological tests and brain structure with MRI. Multivariable linear models were used to assess the associations between DGI, cognitive z scores, and brain structure. Effect modification for T2D was examined with a DGI × T2D product term. RESULTS The mean age of the sample was 69.9 y (SD 7.4 y), with 57.1% men. The mean DGI was 54.8 (SD 10.7; range 24.1-84.6). No associations were observed between the Australian DGI and cognition or brain MRI measures. T2D did not modify any associations (P > 0.05). CONCLUSIONS This is the first study to investigate associations between adherence to the ADG and brain health in the older adults with and without T2D. Future prospective studies are required to clarify if there are long-term associations. Copyright © The Author(s) 2020.BACKGROUND With the increasing demand for body contouring procedures in the US over the past two decades, more surgeons with diverse specialty training are performing these procedures. However, little is known regarding the comparative outcomes of these patients. OBJECTIVES The purpose of this study was to compare outcomes of body contouring procedures based on the specialty training of the surgeon. METHODS Data from the American College of Surgeons National Surgical Quality Improvement Program (2005-2015) were reviewed for all body contouring procedures. Patients were stratified by surgeon training (Plastic Surgery [PS] vs. General Surgery [GS]). Descriptive statistics and regression analyses were used to evaluate differences in outcomes. RESULTS A total of 11,658 patients were included; 9,502 PS cases and 2,156 GS cases. Most were women (90.4%), aged 40 to 59 (52.7%) and White (79.5%). Compared to PS patients, GS patients were more likely obese (61.4% vs. 40.6%), smokers (13.6% vs. 9.8%), and with ASA≥3 (35.3% vs. 18.6%) (all P less then 0.001). Abdominal contouring procedures were the most common (76%) cases. Multivariate regression revealed that compared to PS cases, those performed by GS were associated with increased wound and infectious complications (adjusted Odds Ratio, aOR 1.81; 95% Confidence Interval, 95%CI 1.44 - 2.27), reoperation (aOR 1.85; 95%CI 1.31 - 2.62), and predicted mean length of stay (1.12 d; 95%CI 0.64 - 1.60). CONCLUSIONS The variable outcomes in body contouring procedures performed by PS compared to GS may imply procedural-algorithmic differences between the subspecialties leading to the noted outcome differential. © 2020 The Aesthetic Society. Reprints and permission journals.permissions@oup.com.
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  • Moreover, one case also necessitated rectosigmoidian resection followed by colorectal anastomosis. In all cases no residual disease was encountered at the end of the debulking surgery. CONCLUSION Urinary tract resections might be needed in order to maximize the debulking effort in patients presenting endometrial stromal sarcomas. BACKGROUND/AIM During the last decade it has been widely demonstrated that venous involvement in pancreatic head cancer is not a sign of poor prognostic, while surgery with curative intent is feasible and with encouraging results. However, the location and extent of venous invasion can occasionally pose serious problems in terms of reconstruction. The aim of the paper is to describe a case in which total superior mesenteric and portal vein resection followed by reconstruction were successfully performed. CASE REPORT We present the case of a 74-year-old patient submitted to surgery for locally advanced pancreatic cancer invading the portal and superior mesenteric veins. Surgery consisting of pancreatoduodenectomy en bloc with portal vein and superior mesenteric vein resection was performed. The venous axis was reconstructed by using a venous cadaveric allograft originating from the external iliac vein. https://www.selleckchem.com/products/atezolizumab.html The postoperative outcome was favorable and the histopathological studies confirmed the local invasion of the resected venous structures. CONCLUSION The cadaveric venous allograft can be safely used in order to reconstruct the venous axis following extended vascular resections for pancreatic cancer. BACKGROUND/AIM Circulating tumor cells (CTCs) can be a surrogate biomarker of prospective prognosis. Surgical manipulation can promote the dissemination of CTCs. Prognosis improvement is expected with the no-touch isolation technique (NTIT), preventing surgical manipulation. The Wedge resection of the tumor site before lobectomy could prevent surgical manipulation during lobectomy for non-small cell lung cancer (NSCLC) and reduce the shedding of tumor cells, similar to a NTIT. This study aimed to evaluate the effect of wedge resection technique. PATIENTS AND METHODS A total of 624 resected NSCLC patients were retrospectively analyzed. Patients were divided in two groups Wedge and Non-Wedge. Overall survival (OS) curves were plotted using the Kaplan-Meier method. RESULTS The 5-year OS rates were 89.9% and 84.0% in the Wedge and Non-Wedge groups, respectively (p=0.033). CONCLUSION The OS in the Wedge group was significantly better than that in the Non-Wedge group. Wedge resection technique for NSCLC may be a NTIT. BACKGROUND/AIM Physical function is known to decrease after hematopoietic stem cell transplantation (HSCT), with the most substantial impairment noted at 90 days post-transplantation. Little is known about the natural course of physical function during the acute post-transplant period preciously. The aim of the study was to monitor the changes in physical function through serial evaluations of the physical function, and identify the effect of physical function on QoL during the acute post-transplant period. PATIENTS AND METHODS This prospective cohort study included 41 patients admitted for planned autologous or allogeneic HSCT. Physical impairment was evaluated with decrease in the de Morton Mobility Index (DEMMI) every week and defined as a DEMMI score of more than 2 points after HSCT. The outcome variables for QoL included visual analogue scale (VAS), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), and Zung Self-rating Depression Scale (SDS) at enrodetected in the early period after HSCT. Therefore, monitoring of standardized functional outcome measures is important to prevent physical impairment following HSCT. BACKGROUND/AIM Cancer patients with metastatic disease require personalized treatment regimens. This study was performed to identify prognostic factors for overall survival (OS) following irradiation of bone metastases from kidney cancer. PATIENTS AND METHODS Data of 29 patients irradiated for bone metastases from kidney cancer were retrospectively evaluated. Ten factors were analyzed, including age, gender, performance score, interval from diagnosis of kidney cancer until radiotherapy for bone metastases, visceral metastases, other bone metastases, metastatic sites, number of irradiated sites, surgery of irradiated sites and systemic treatment prior to radiotherapy. RESULTS Using univariate analyses, a longer interval from diagnosis of kidney cancer radiotherapy was associated with better OS (p=0.012). Using Cox regression analysis, this factor remained significant (risk ratio=3.54, p=0.012). CONCLUSION The interval from diagnosis of kidney cancer until radiotherapy is an independent prognostic factor associated with OS following irradiation of bone metastases from kidney cancer. This type of data can help personalize radiation programs. BACKGROUND/AIM To report the outcomes of patients with prostate cancer treated with dose-escalated radiotherapy over a 15-year period at our Institution. PATIENTS AND METHODS Patients with biopsy-proven cT1-4N0M0 disease who received radical external beam radiotherapy (EBRT) were reviewed. The endpoints were 5-year overall survival (OS), freedom from biochemical failure (FFBF) and late treatment toxicities. RESULTS A total of 236 patients were eligible. Median follow-up was 70 months. Low-, intermediate- and high-risk disease was found in 9%; 29% and 62% of patients, respectively. The median radiation dose was 73.8 Gy. Overall 42% of patients had dose escalation to >74 Gy. Five-year OS and FFBF were 95.2%/81.6%/75.4% and 95.0%/98.0%/82.0% for low-/intermediate-/high-risk patients, respectively. Dose escalation to >74 Gy did not improve FFBF (hazard ratio=0.97, 95% confidence intervaI=0.43-2.19, p=0.93) and was associated with a 4.3-fold increase in the odds of grade 3 or more rectal bleeding (p74 Gy did not improve OS or FFBF but was associated with a higher rate of grade 3 or more rectal haemorrhage. BACKGROUND/AIM Spontaneous recanalization of coronary thrombus (SRCT) is a rare in vivo appearance, with a nonspecific angiographic aspect. The aim of this study was to investigate the importance of optical coherence tomography (OCT) use for SRCT identification, characterization of pathogenic mechanisms and optimal treatment. PATIENTS AND METHODS We retrospectively analyzed all patients with angiographic suspicion of SRCT who underwent coronary angiography for suspected coronary artery disease and afterward investigated by OCT imaging. RESULTS We identified 28 cases with angiographic suspicion of SCRT (0.41% of CA) and confirmed it in 4 patients (0.05% of CA). OCT provided insight about the underlying SRCT mechanism possible complicated atherosclerotic plaques in two cases and, respectively, spontaneous coronary artery dissection in other two cases. OCT provided accurate lesion assessment and offered optimal PCI materials selection. CONCLUSION Besides providing the diagnosis, OCT also improved characterization of SRCT pathogenic mechanisms, in the four confirmed SRCT cases, supporting the role of coronary wall in situ complications, namely dissection of an atherosclerotic plaque or spontaneous dissection of a normal coronary wall.
    Moreover, one case also necessitated rectosigmoidian resection followed by colorectal anastomosis. In all cases no residual disease was encountered at the end of the debulking surgery. CONCLUSION Urinary tract resections might be needed in order to maximize the debulking effort in patients presenting endometrial stromal sarcomas. BACKGROUND/AIM During the last decade it has been widely demonstrated that venous involvement in pancreatic head cancer is not a sign of poor prognostic, while surgery with curative intent is feasible and with encouraging results. However, the location and extent of venous invasion can occasionally pose serious problems in terms of reconstruction. The aim of the paper is to describe a case in which total superior mesenteric and portal vein resection followed by reconstruction were successfully performed. CASE REPORT We present the case of a 74-year-old patient submitted to surgery for locally advanced pancreatic cancer invading the portal and superior mesenteric veins. Surgery consisting of pancreatoduodenectomy en bloc with portal vein and superior mesenteric vein resection was performed. The venous axis was reconstructed by using a venous cadaveric allograft originating from the external iliac vein. https://www.selleckchem.com/products/atezolizumab.html The postoperative outcome was favorable and the histopathological studies confirmed the local invasion of the resected venous structures. CONCLUSION The cadaveric venous allograft can be safely used in order to reconstruct the venous axis following extended vascular resections for pancreatic cancer. BACKGROUND/AIM Circulating tumor cells (CTCs) can be a surrogate biomarker of prospective prognosis. Surgical manipulation can promote the dissemination of CTCs. Prognosis improvement is expected with the no-touch isolation technique (NTIT), preventing surgical manipulation. The Wedge resection of the tumor site before lobectomy could prevent surgical manipulation during lobectomy for non-small cell lung cancer (NSCLC) and reduce the shedding of tumor cells, similar to a NTIT. This study aimed to evaluate the effect of wedge resection technique. PATIENTS AND METHODS A total of 624 resected NSCLC patients were retrospectively analyzed. Patients were divided in two groups Wedge and Non-Wedge. Overall survival (OS) curves were plotted using the Kaplan-Meier method. RESULTS The 5-year OS rates were 89.9% and 84.0% in the Wedge and Non-Wedge groups, respectively (p=0.033). CONCLUSION The OS in the Wedge group was significantly better than that in the Non-Wedge group. Wedge resection technique for NSCLC may be a NTIT. BACKGROUND/AIM Physical function is known to decrease after hematopoietic stem cell transplantation (HSCT), with the most substantial impairment noted at 90 days post-transplantation. Little is known about the natural course of physical function during the acute post-transplant period preciously. The aim of the study was to monitor the changes in physical function through serial evaluations of the physical function, and identify the effect of physical function on QoL during the acute post-transplant period. PATIENTS AND METHODS This prospective cohort study included 41 patients admitted for planned autologous or allogeneic HSCT. Physical impairment was evaluated with decrease in the de Morton Mobility Index (DEMMI) every week and defined as a DEMMI score of more than 2 points after HSCT. The outcome variables for QoL included visual analogue scale (VAS), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), and Zung Self-rating Depression Scale (SDS) at enrodetected in the early period after HSCT. Therefore, monitoring of standardized functional outcome measures is important to prevent physical impairment following HSCT. BACKGROUND/AIM Cancer patients with metastatic disease require personalized treatment regimens. This study was performed to identify prognostic factors for overall survival (OS) following irradiation of bone metastases from kidney cancer. PATIENTS AND METHODS Data of 29 patients irradiated for bone metastases from kidney cancer were retrospectively evaluated. Ten factors were analyzed, including age, gender, performance score, interval from diagnosis of kidney cancer until radiotherapy for bone metastases, visceral metastases, other bone metastases, metastatic sites, number of irradiated sites, surgery of irradiated sites and systemic treatment prior to radiotherapy. RESULTS Using univariate analyses, a longer interval from diagnosis of kidney cancer radiotherapy was associated with better OS (p=0.012). Using Cox regression analysis, this factor remained significant (risk ratio=3.54, p=0.012). CONCLUSION The interval from diagnosis of kidney cancer until radiotherapy is an independent prognostic factor associated with OS following irradiation of bone metastases from kidney cancer. This type of data can help personalize radiation programs. BACKGROUND/AIM To report the outcomes of patients with prostate cancer treated with dose-escalated radiotherapy over a 15-year period at our Institution. PATIENTS AND METHODS Patients with biopsy-proven cT1-4N0M0 disease who received radical external beam radiotherapy (EBRT) were reviewed. The endpoints were 5-year overall survival (OS), freedom from biochemical failure (FFBF) and late treatment toxicities. RESULTS A total of 236 patients were eligible. Median follow-up was 70 months. Low-, intermediate- and high-risk disease was found in 9%; 29% and 62% of patients, respectively. The median radiation dose was 73.8 Gy. Overall 42% of patients had dose escalation to >74 Gy. Five-year OS and FFBF were 95.2%/81.6%/75.4% and 95.0%/98.0%/82.0% for low-/intermediate-/high-risk patients, respectively. Dose escalation to >74 Gy did not improve FFBF (hazard ratio=0.97, 95% confidence intervaI=0.43-2.19, p=0.93) and was associated with a 4.3-fold increase in the odds of grade 3 or more rectal bleeding (p74 Gy did not improve OS or FFBF but was associated with a higher rate of grade 3 or more rectal haemorrhage. BACKGROUND/AIM Spontaneous recanalization of coronary thrombus (SRCT) is a rare in vivo appearance, with a nonspecific angiographic aspect. The aim of this study was to investigate the importance of optical coherence tomography (OCT) use for SRCT identification, characterization of pathogenic mechanisms and optimal treatment. PATIENTS AND METHODS We retrospectively analyzed all patients with angiographic suspicion of SRCT who underwent coronary angiography for suspected coronary artery disease and afterward investigated by OCT imaging. RESULTS We identified 28 cases with angiographic suspicion of SCRT (0.41% of CA) and confirmed it in 4 patients (0.05% of CA). OCT provided insight about the underlying SRCT mechanism possible complicated atherosclerotic plaques in two cases and, respectively, spontaneous coronary artery dissection in other two cases. OCT provided accurate lesion assessment and offered optimal PCI materials selection. CONCLUSION Besides providing the diagnosis, OCT also improved characterization of SRCT pathogenic mechanisms, in the four confirmed SRCT cases, supporting the role of coronary wall in situ complications, namely dissection of an atherosclerotic plaque or spontaneous dissection of a normal coronary wall.
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  • This paper reports 2 cases of female carriers of the FMR1 premutation for developing spontaneous coronary artery dissection (SCAD). These women had classical presentations of premutation symptoms, including anxiety, depression, and connective tissue problems, all of which can contribute to SCAD. These cases suggest a possible connection between the fragile X premutation and a predisposition to SCAD.Serratus anterior plane blocks may provide analgesia for rib fractures, thoracic surgery and breast surgery. There remains uncertainty regarding the location of injection, be it superficial or deep to the serratus anterior muscle. We describe the case of a 63-year-old ASA physical status 3 woman undergoing a wire-guided wide local excision of a right breast lump. A modified right serratus anterior plane block was performed under ultrasound guidance, injecting 20 ml of bupivacaine 0.25% deep to the serratus anterior muscle. No immediate complications were noted. Intra-operatively the patient developed arterial desaturation associated with high airway pressures. A subsequent chest radiograph in the post-anaesthetic care unit demonstrated a large right-sided pneumothorax which was treated with immediate needle decompression and chest drain insertion. This is the first case of pneumothorax reported from this approach to serratus anterior plane blockade and serves as a reminder of a potential serious complication. © 2020 Association of Anaesthetists.A 45-year-old man suffered compartment syndrome of the hands as a complication of prolonged cardiopulmonary resuscitation. He was admitted following a hypothermic out-of-hospital cardiac arrest due to cold-water submersion. The patient was in cardiac arrest for 4 h with mechanical cardiopulmonary resuscitation delivered using the **** University Cardiac Arrest System (Jolife AB, ****, Sweden). Cardiopulmonary resuscitation along with aggressive rewarming achieved return of spontaneous circulation. He developed compartment syndrome in his left hand which was likely exacerbated by having his arm strapped to the **** University Cardiac Arrest System device throughout the resuscitation. The compartment syndrome was managed conservatively. Despite preservation of neurological function the patient died of complications from the cardiac arrest after an extended intensive care unit stay. https://www.selleckchem.com/products/rgt-018.html We recommend healthcare providers unstrap patient's hands during prolonged mechanical cardiopulmonary resuscitation. © 2020 Association of Anaesthetists.We report a case of local anaesthetic toxicity in an anaesthetic trainee participating as a subject for an awake tracheal intubation training course. The trainee experienced symptoms of toxicity despite the dose of lidocaine administered being less than the maximum safe dose recommended for airway topicalisation. We argue this highlights the variability in absorption of local anaesthetic and the importance of safety during awake tracheal intubation training courses. It is essential to use the minimum safe dose of local anaesthetic required during topicalisation for awake tracheal intubation. We have now made it our course policy that participants cannot undergo awake tracheal intubation less than 2 weeks before a period of coryzal illness. We recommend that operators remain vigilant for signs of local anaesthetic toxicity when undertaking this procedure and adhere to newly published Difficult Airway Society awake tracheal intubation guidelines. © 2020 Association of Anaesthetists.A plethora of biotechnological methodologies is used to authenticate quality olive oils. Among the DNA-based approaches, SNPs and SSRs combined with high resolution melting (HRM) provide certain advantages such as speed, simplicity and reliability. SNP-HRM and SSR-HRM were used for the authentication of monovarietal olive oils as well as the quantification of varietal composition in olive oil DNA admixtures and olive oil blends of two different cultivars. The SSR-HRM was more efficient in distinguishing monovarietal olive oils while the SNP-HRM assay was more reliable in discriminating olive oil blends. HRM was also used for the detection of adulteration of olive oil with oils of different plant origin by using plastid trnL indels and SNPs. The trnL-indels-HRM showed higher discrimination power than the trnL-SNP-HRM in determining adulteration in olive oil. These results indicate that traceability of adulteration might be more reliable than authentication of the varietal origin in olive oil blends. © 2020 The Authors.Although Amorphous Solid Dispersions (ASDs) effectively increase bioavailability, tablet mass can be high due to the large fraction of excipients needed to stabilize the amorphous drug in the solid state, extend drug supersaturation in solution and achieve robust manufacturability. The aim of this work was to reduce tablet mass of an ASD tablet comprising a low glass transition temperature (Tg), rapidly crystallizing drug without compromising these key attributes. In this approach, erlotinib (Tg = 42 °C, Tm/Tg = 1.4 K/K) was spray dried with the high Tg polymer poly(methyl methacrylate-co-methacrylic acid) (Eudragit® L100, Evonik) (Tg = 187 °C) to facilitate high drug loading while maintaining physical stability. Hydroxypropyl methylcellulose acetate succinate (HPMCAS) (AQOAT® HF, Shin-Etsu) was granulated with the ASD to extend supersaturation in solution. For comparison, a benchmark ASD was spray dried at a lower drug loading with HPMCAS-H (Tg = 119 °C). This High Loaded Dosage Form (HLDF) approach reduced tablet mass by 40%, demonstrated similar physical stability and in vitro performance as the benchmark and exhibited excellent downstream manufacturability. Strategically combining two different polymers in a tablet to maintain physical stability and sustain supersaturation in solution can decrease tablet mass of some low Tg, rapidly crystallizing amorphous drugs. © 2020 The Authors.Simultaneous nitrification-denitrification (SND) is, in theory, a key advantage of aerobic granular sludge systems over conventional activated sludge systems. But practical experience and literature suggests that SND and thus total nitrogen removal are limited during treatment of municipal wastewater using AGS systems. This study thus aims at quantifying the extent and understanding the mechanisms of SND during treatment of municipal wastewater with aerobic granular sludge (AGS) systems. Experiments (long-term and batch-tests) as well as mathematical modelling were performed. Our experimental results demonstrate that SND is significantly limited during treatment of low-strength municipal wastewater with AGS systems (14-39%), while almost full SND is observed when treating synthetic influent containing only diffusible substrate (90%). Our simulations demonstrate that the main mechanisms behind limited SND are (1) the dynamics of anoxic zone formation inside the granule, (2) the diffusibility and availability of electron-donors in those zones and (3) the aeration mode.
    This paper reports 2 cases of female carriers of the FMR1 premutation for developing spontaneous coronary artery dissection (SCAD). These women had classical presentations of premutation symptoms, including anxiety, depression, and connective tissue problems, all of which can contribute to SCAD. These cases suggest a possible connection between the fragile X premutation and a predisposition to SCAD.Serratus anterior plane blocks may provide analgesia for rib fractures, thoracic surgery and breast surgery. There remains uncertainty regarding the location of injection, be it superficial or deep to the serratus anterior muscle. We describe the case of a 63-year-old ASA physical status 3 woman undergoing a wire-guided wide local excision of a right breast lump. A modified right serratus anterior plane block was performed under ultrasound guidance, injecting 20 ml of bupivacaine 0.25% deep to the serratus anterior muscle. No immediate complications were noted. Intra-operatively the patient developed arterial desaturation associated with high airway pressures. A subsequent chest radiograph in the post-anaesthetic care unit demonstrated a large right-sided pneumothorax which was treated with immediate needle decompression and chest drain insertion. This is the first case of pneumothorax reported from this approach to serratus anterior plane blockade and serves as a reminder of a potential serious complication. © 2020 Association of Anaesthetists.A 45-year-old man suffered compartment syndrome of the hands as a complication of prolonged cardiopulmonary resuscitation. He was admitted following a hypothermic out-of-hospital cardiac arrest due to cold-water submersion. The patient was in cardiac arrest for 4 h with mechanical cardiopulmonary resuscitation delivered using the Lund University Cardiac Arrest System (Jolife AB, Lund, Sweden). Cardiopulmonary resuscitation along with aggressive rewarming achieved return of spontaneous circulation. He developed compartment syndrome in his left hand which was likely exacerbated by having his arm strapped to the Lund University Cardiac Arrest System device throughout the resuscitation. The compartment syndrome was managed conservatively. Despite preservation of neurological function the patient died of complications from the cardiac arrest after an extended intensive care unit stay. https://www.selleckchem.com/products/rgt-018.html We recommend healthcare providers unstrap patient's hands during prolonged mechanical cardiopulmonary resuscitation. © 2020 Association of Anaesthetists.We report a case of local anaesthetic toxicity in an anaesthetic trainee participating as a subject for an awake tracheal intubation training course. The trainee experienced symptoms of toxicity despite the dose of lidocaine administered being less than the maximum safe dose recommended for airway topicalisation. We argue this highlights the variability in absorption of local anaesthetic and the importance of safety during awake tracheal intubation training courses. It is essential to use the minimum safe dose of local anaesthetic required during topicalisation for awake tracheal intubation. We have now made it our course policy that participants cannot undergo awake tracheal intubation less than 2 weeks before a period of coryzal illness. We recommend that operators remain vigilant for signs of local anaesthetic toxicity when undertaking this procedure and adhere to newly published Difficult Airway Society awake tracheal intubation guidelines. © 2020 Association of Anaesthetists.A plethora of biotechnological methodologies is used to authenticate quality olive oils. Among the DNA-based approaches, SNPs and SSRs combined with high resolution melting (HRM) provide certain advantages such as speed, simplicity and reliability. SNP-HRM and SSR-HRM were used for the authentication of monovarietal olive oils as well as the quantification of varietal composition in olive oil DNA admixtures and olive oil blends of two different cultivars. The SSR-HRM was more efficient in distinguishing monovarietal olive oils while the SNP-HRM assay was more reliable in discriminating olive oil blends. HRM was also used for the detection of adulteration of olive oil with oils of different plant origin by using plastid trnL indels and SNPs. The trnL-indels-HRM showed higher discrimination power than the trnL-SNP-HRM in determining adulteration in olive oil. These results indicate that traceability of adulteration might be more reliable than authentication of the varietal origin in olive oil blends. © 2020 The Authors.Although Amorphous Solid Dispersions (ASDs) effectively increase bioavailability, tablet mass can be high due to the large fraction of excipients needed to stabilize the amorphous drug in the solid state, extend drug supersaturation in solution and achieve robust manufacturability. The aim of this work was to reduce tablet mass of an ASD tablet comprising a low glass transition temperature (Tg), rapidly crystallizing drug without compromising these key attributes. In this approach, erlotinib (Tg = 42 °C, Tm/Tg = 1.4 K/K) was spray dried with the high Tg polymer poly(methyl methacrylate-co-methacrylic acid) (Eudragit® L100, Evonik) (Tg = 187 °C) to facilitate high drug loading while maintaining physical stability. Hydroxypropyl methylcellulose acetate succinate (HPMCAS) (AQOAT® HF, Shin-Etsu) was granulated with the ASD to extend supersaturation in solution. For comparison, a benchmark ASD was spray dried at a lower drug loading with HPMCAS-H (Tg = 119 °C). This High Loaded Dosage Form (HLDF) approach reduced tablet mass by 40%, demonstrated similar physical stability and in vitro performance as the benchmark and exhibited excellent downstream manufacturability. Strategically combining two different polymers in a tablet to maintain physical stability and sustain supersaturation in solution can decrease tablet mass of some low Tg, rapidly crystallizing amorphous drugs. © 2020 The Authors.Simultaneous nitrification-denitrification (SND) is, in theory, a key advantage of aerobic granular sludge systems over conventional activated sludge systems. But practical experience and literature suggests that SND and thus total nitrogen removal are limited during treatment of municipal wastewater using AGS systems. This study thus aims at quantifying the extent and understanding the mechanisms of SND during treatment of municipal wastewater with aerobic granular sludge (AGS) systems. Experiments (long-term and batch-tests) as well as mathematical modelling were performed. Our experimental results demonstrate that SND is significantly limited during treatment of low-strength municipal wastewater with AGS systems (14-39%), while almost full SND is observed when treating synthetic influent containing only diffusible substrate (90%). Our simulations demonstrate that the main mechanisms behind limited SND are (1) the dynamics of anoxic zone formation inside the granule, (2) the diffusibility and availability of electron-donors in those zones and (3) the aeration mode.
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  • Mung bean is gaining attention as a sustainable and economic source of plant protein. The current study evaluates the techno-functionality, anti-nutrient properties, in vivo protein quality and toxicity of texturized mung bean protein (TMBP) produced under optimized conditions. Our work successfully produces TMBP with improved techno-functionalities that are crucial for meat-based food applications, credited to retained juiciness and fat-binding ability. Alkaline extraction and extrusion significantly reduce trypsin inhibitor, phytic acid and tannin content in TMBP. An in vivo study using Sprague-Dawley rats reveals the good protein quality of TMBP, with a true protein digestibility of 99.26% resembling casein (99.36%, control protein), a net protein utilization of 63.99% and a biological value of 64.46%. The good protein quality, increased lean muscle mass along with reduced cholesterol and triglyceride secures TMBP's potential as a Protein meal replacer and dietary suplement. Non-toxicity of TMBP is confirmed by normal serum biochemical parameters and healthy organs, ascertaining the safety of alkaline extraction. The current study elucidates the production of TMBP with improved techno-functionalities (for meat-based food applications), reduced anti-nutritional factors and high quality (for weight-watchers and malnourished individuals).Al(iii) complexes are extensively studied as [18F]fluoride carriers in positron emission tomography. However, our limited knowledge on their thermodynamic and kinetic properties has hindered efforts to easily prepare radiochemically pure compounds while simultaneously reducing the overall labeling time. https://www.selleckchem.com/products/vx-984.html Thus, to improve our understanding of fluoride binding to coordinatively unsaturated Al(iii) complexes, we investigated the ternary system Al(iii)-H3NTA-F- (H3NTA = nitrilo-triacetic acid) by NMR, potentiometry and X-ray diffraction. Our results show that the [Al(NTA)] complex binds two water molecules, which are replaced by fluorides. Individual species and isomers show separate 19F NMR signals and different stability constants. The two available positions on the [Al(NTA)] complex feature significantly different properties in terms of basicity of the coordinated water molecules and preferential binding of fluoride anions. Fluorides are effectively bound in weakly acidic or neutral solutions, whereas hydroxido species are preferentially formed in alkaline solutions. Our experimental observations were rationalized by theoretical calculations predictions of the energy ordering of complexes and isomers, interpretation of 19F NMR chemical shifts, and natural bonding orbital analysis. Radiolabeling of [Al(NTA)] with [18F]fluoride gave low yields that confirmed a high affinity of the complex for hydroxide anions.While the mechanotransduction-induced fate of adult neural stem/progenitor cells (NPCs) is relatively known, how substrate stiffness regulates the temporal evolution of the biomechanics and phenotype of developmentally relevant human fetal NPCs (hNPCs) and their mechanosensing pathways remain unknown. Here, we primed hNPCs on tissue-culture plastic (TCPS) for 3 days in non-differentiating medium before transferring to TCPS or Geltrex™ gels ( glia subtypes. Higher stress fiber density in cells on stiffer gels explains their significantly different biomechanical properties on these gels. Blebbistatin treatment caused cell polarization, lowered elastic modulus, and enhanced tether forces, implicating the role of non-muscle myosin-II in hNPC mechanosensing, adaptability, and thereby mechanics. Such substrate-mediated temporal evolution of hNPCs guide design of smart scaffolds to investigate morphogenesis, disease modeling, stem cell biology, and biomaterials for tissue engineering.Fine particle samples were collected during summer at an urban (LIM) and a rural/background (AGM) site of Cyprus. They were analyzed for pinene and isoprene secondary organic aerosol (PSOA-ISOA) tracers, linear dicarboxylic acids (DCAs), hydroxyacids (HAs), aromatic acids (AAs), monocarboxylic acids (MCAs) and levoglucosan by GC/MS with prior 3-step derivatization. DCAs, AAs, MCAs and levoglucosan exhibited significantly higher concentrations (p less then 0.05) in LIM, PSOAs and ISOAs in AGM (p less then 0.05), whereas mixed trends were found for HAs. Among DCAs, succinic was the most abundant in both sites, accounting for 42.5% and 36.5% of the total DCAs in LIM and AGM respectively, followed by adipic in LIM (20.1%) and azelaic in AGM (22.4%). Malic, phthalic and palmitic acids were the dominant HA, AA and MCA, respectively. Regarding PSOAs, significant differences were observed between the two sites, with the first-generation products accounting for 59.8% of the total measured PSOAs in AGM, but were remarkably lowered (10.3%) in LIM indicating that they were highly oxidized. 2-Methylerythritol was the dominant ISOA tracer in both sites; nevertheless the elevated relative abundance of 2-methylglyceric acid in LIM implies the influences of higher NOx levels. The increased O3 levels observed in AGM appear to have a significant impact on SOA formation. Source apportionment tools employed revealed factors related to secondary formation processes including oxidation of unsaturated fatty acids, pinene, isoprene and anthropogenic VOCs and factors associated with primary sources such as biomass burning, plant emissions and/or cooking and motor exhaust, with noteworthy differences observed between the two areas.Helicobacter spp. are Gram-negative bacteria that cause a spectrum of disease in the gut, biliary tree and liver. Many Helicobacter spp. produce a range of cholesteryl α-glucosides that have the potential to act as pathogen associated molecular patterns. We report a highly stereoselective α-glucosylation of cholesterol using 3,4,6-tri-O-acetyl-2-O-benzyl-d-glucopyranosyl N-phenyl-2,2,2-trifluoroacetimidate, which allowed the synthesis of cholesteryl α-glucoside (αCG) and representative Helicobacter spp. cholesteryl 6-O-acyl-α-glucosides (αCAGs; acyl = C120, 140, C160, C180, C181). All αCAGs, irrespective of the nature of their acyl chain composition, strongly agonised signalling through the C-type lectin receptor Mincle from human and mouse to similar degrees. By contrast, αCG only weakly signalled through human Mincle, and did not signal through mouse Mincle. These results provide a molecular basis for understanding of the immunobiology of non-pylori Helicobacter infections in humans and other animals.
    Mung bean is gaining attention as a sustainable and economic source of plant protein. The current study evaluates the techno-functionality, anti-nutrient properties, in vivo protein quality and toxicity of texturized mung bean protein (TMBP) produced under optimized conditions. Our work successfully produces TMBP with improved techno-functionalities that are crucial for meat-based food applications, credited to retained juiciness and fat-binding ability. Alkaline extraction and extrusion significantly reduce trypsin inhibitor, phytic acid and tannin content in TMBP. An in vivo study using Sprague-Dawley rats reveals the good protein quality of TMBP, with a true protein digestibility of 99.26% resembling casein (99.36%, control protein), a net protein utilization of 63.99% and a biological value of 64.46%. The good protein quality, increased lean muscle mass along with reduced cholesterol and triglyceride secures TMBP's potential as a Protein meal replacer and dietary suplement. Non-toxicity of TMBP is confirmed by normal serum biochemical parameters and healthy organs, ascertaining the safety of alkaline extraction. The current study elucidates the production of TMBP with improved techno-functionalities (for meat-based food applications), reduced anti-nutritional factors and high quality (for weight-watchers and malnourished individuals).Al(iii) complexes are extensively studied as [18F]fluoride carriers in positron emission tomography. However, our limited knowledge on their thermodynamic and kinetic properties has hindered efforts to easily prepare radiochemically pure compounds while simultaneously reducing the overall labeling time. https://www.selleckchem.com/products/vx-984.html Thus, to improve our understanding of fluoride binding to coordinatively unsaturated Al(iii) complexes, we investigated the ternary system Al(iii)-H3NTA-F- (H3NTA = nitrilo-triacetic acid) by NMR, potentiometry and X-ray diffraction. Our results show that the [Al(NTA)] complex binds two water molecules, which are replaced by fluorides. Individual species and isomers show separate 19F NMR signals and different stability constants. The two available positions on the [Al(NTA)] complex feature significantly different properties in terms of basicity of the coordinated water molecules and preferential binding of fluoride anions. Fluorides are effectively bound in weakly acidic or neutral solutions, whereas hydroxido species are preferentially formed in alkaline solutions. Our experimental observations were rationalized by theoretical calculations predictions of the energy ordering of complexes and isomers, interpretation of 19F NMR chemical shifts, and natural bonding orbital analysis. Radiolabeling of [Al(NTA)] with [18F]fluoride gave low yields that confirmed a high affinity of the complex for hydroxide anions.While the mechanotransduction-induced fate of adult neural stem/progenitor cells (NPCs) is relatively known, how substrate stiffness regulates the temporal evolution of the biomechanics and phenotype of developmentally relevant human fetal NPCs (hNPCs) and their mechanosensing pathways remain unknown. Here, we primed hNPCs on tissue-culture plastic (TCPS) for 3 days in non-differentiating medium before transferring to TCPS or Geltrex™ gels ( glia subtypes. Higher stress fiber density in cells on stiffer gels explains their significantly different biomechanical properties on these gels. Blebbistatin treatment caused cell polarization, lowered elastic modulus, and enhanced tether forces, implicating the role of non-muscle myosin-II in hNPC mechanosensing, adaptability, and thereby mechanics. Such substrate-mediated temporal evolution of hNPCs guide design of smart scaffolds to investigate morphogenesis, disease modeling, stem cell biology, and biomaterials for tissue engineering.Fine particle samples were collected during summer at an urban (LIM) and a rural/background (AGM) site of Cyprus. They were analyzed for pinene and isoprene secondary organic aerosol (PSOA-ISOA) tracers, linear dicarboxylic acids (DCAs), hydroxyacids (HAs), aromatic acids (AAs), monocarboxylic acids (MCAs) and levoglucosan by GC/MS with prior 3-step derivatization. DCAs, AAs, MCAs and levoglucosan exhibited significantly higher concentrations (p less then 0.05) in LIM, PSOAs and ISOAs in AGM (p less then 0.05), whereas mixed trends were found for HAs. Among DCAs, succinic was the most abundant in both sites, accounting for 42.5% and 36.5% of the total DCAs in LIM and AGM respectively, followed by adipic in LIM (20.1%) and azelaic in AGM (22.4%). Malic, phthalic and palmitic acids were the dominant HA, AA and MCA, respectively. Regarding PSOAs, significant differences were observed between the two sites, with the first-generation products accounting for 59.8% of the total measured PSOAs in AGM, but were remarkably lowered (10.3%) in LIM indicating that they were highly oxidized. 2-Methylerythritol was the dominant ISOA tracer in both sites; nevertheless the elevated relative abundance of 2-methylglyceric acid in LIM implies the influences of higher NOx levels. The increased O3 levels observed in AGM appear to have a significant impact on SOA formation. Source apportionment tools employed revealed factors related to secondary formation processes including oxidation of unsaturated fatty acids, pinene, isoprene and anthropogenic VOCs and factors associated with primary sources such as biomass burning, plant emissions and/or cooking and motor exhaust, with noteworthy differences observed between the two areas.Helicobacter spp. are Gram-negative bacteria that cause a spectrum of disease in the gut, biliary tree and liver. Many Helicobacter spp. produce a range of cholesteryl α-glucosides that have the potential to act as pathogen associated molecular patterns. We report a highly stereoselective α-glucosylation of cholesterol using 3,4,6-tri-O-acetyl-2-O-benzyl-d-glucopyranosyl N-phenyl-2,2,2-trifluoroacetimidate, which allowed the synthesis of cholesteryl α-glucoside (αCG) and representative Helicobacter spp. cholesteryl 6-O-acyl-α-glucosides (αCAGs; acyl = C120, 140, C160, C180, C181). All αCAGs, irrespective of the nature of their acyl chain composition, strongly agonised signalling through the C-type lectin receptor Mincle from human and mouse to similar degrees. By contrast, αCG only weakly signalled through human Mincle, and did not signal through mouse Mincle. These results provide a molecular basis for understanding of the immunobiology of non-pylori Helicobacter infections in humans and other animals.
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  • Herein, we review the progress in the use of cellular and molecular markers for the accurate identification of PCNs.Metabolic syndrome (MetS) describes a set of risk factors that can eventually lead to the occurrence of cardiovascular and cerebrovascular disease. A detailed understanding of the MetS mechanism will be helpful in developing effective prevention strategies and appropriate intervention tools. In this article, we discuss the relationship between the clinical symptoms of MetS and differences in the gut microbial community compared with healthy individuals, characterized by the proliferation of potentially harmful bacteria and the inhibition of beneficial ones. Interactions between gut microbiota and host metabolism have been shown to be mediated by a number of factors, including inflammation caused by gut barrier defects, short-chain fatty acids metabolism, and bile acid metabolism. However, although we can clearly establish a causal relationship between gut microbial profiles and MetS in animal experiments, the relationship between them is still controversial in humans. Therefore, we need more clinical studies to augment our understanding of how we can manipulate the gut microbiota and address the role of the gut microbiota in the prevention and treatment of MetS.The human gastrointestinal tract accommodates an entire micro-environment for divergent physiologic processes, the dysbiosis of this micro-ecology has a strong inter-action with the pathogenesis of inflammatory bowel disease (IBD). In the past few years, with the advances in the understanding of microbiome, its metabolites and further application of next generation sequencing, analysis of dynamic alteration of gut micro-environment was realized, which provides numerous information beyond simple microbiota structure or metabolites differences under chronic colitis status. The subsequent intervention strategies targeting the modulation of intestinal micro-environment have been explored as a potential therapy. In this review, we will summarize the recent knowledge about multi-dimensional dysbiosis, the inter-action between fungus and bacteria under inflamed mucosa, and the clinical application of probiotics and fecal microbiota transplantation as a promising therapeutic approach in IBD. Type 2 diabetes mellitus (T2DM), a worldwide epidemic, has caused tremendous economic and social burden, but the pathogenesis remains uncertain. Nowadays, the impact of unrhythmic circadian clock caused by irregular sleep and unhealthy diet on T2DM has started to be increasingly studied. https://www.selleckchem.com/products/vanzacaftor.html However, the contribution of the endogenous circadian clock system to the development of T2DM has not yet been satisfactorily explored. It is now becoming clear that the gut microbiota and the circadian clock interact with each other to regulate the host metabolism. Considering all these above, we review the literature related to the gut microbiota, circadian clock, and T2DM to elucidate the idea that the gut microbiota is closely tied to the regulation of the circadian clock in the development of T2DM, which provides potential for gut microbiota-directed therapies to ameliorate the effects of circadian disruptions linked to the occurrence and development of T2DM.Historically, breast cancer has been regarded as an immunogenic "cold" tumor hence it has not experienced the explosion of immunotherapy. However, the discovery of immune checkpoint inhibitors has made immunotherapy becoming an emerging new treatment modality for breast cancer. This review discusses the immune system, immune features of breast cancer, and the programmed cell death protein-1/programmed cell death protein ligand-1 (PD-1/PD-L1) inhibitors used in the treatment of breast cancer. High T lymphocyte infiltration and mutation burden were observed in triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2 (HER2) breast cancer. Increasing breast cancer immunogenicity and modulating the tumor microenvironment has been reported to improve the therapeutic efficacy of immunotherapy. Recent clinical trials involving PD-1/PD-L1 inhibitors monotherapy in breast cancer has revealed little efficacy and this highlights the need to develop combinations of PD-1/PD-L1 inhibitors with chemotherapy, molecularly targeted therapies, and other immunotherapies to maximize the clinical efficacy. In conclusion, the development of a new combined regimen involving PD-1/PD-L1 inhibitors and the exploration as potential biomarkers is important in breast cancer immunotherapy.BACKGROUND Hyperuricemia and gout have become public health concerns; many important guidelines have recommended xanthine oxidase inhibitors (XOIs) as the first-line uric-lowering therapies (ULTs) to treat chronic gout with hyperuricemia. However, whether treating hyperuricemia and gout with ULTs modifies cardiovascular risks remains controversial. The aim of this study was to assess the incident risk of cardiovascular events (CVE) in hyperuricemia population, assess the cardiovascular benefit-risk of ULTs in hyperuricemia patients with or without gout in diverse cardiovascular risk subgroups, and specify the safety of different ULT. METHODS We searched PubMed, Embase, the Cochrane Library, Wanfang, CQVIP, and China National Knowledge Infrastructure (CNKI) Database for prospective cohort studies and randomized controlled trials (RCTs) in English and Chinese. Potential medications included XOIs, and uricosurics. RCTs were divided into subgroups analysis based on blinding status and patients' history of CV dise incidence of cardiovascular events, and the results suggested that XOIs might reduce the incidence of **** and total CVE. In addition, from the perspective of cardiovascular safety, febuxostat equaled allopurinol in our meta-analysis.BACKGROUND Squamous cell carcinoma (SCC) is the most common malignant tumor of the nail unit. No guidelines currently exist regarding the role of imaging in this specific location. OBJECTIVE To investigate the utility of routine imaging in SCC of the nail apparatus. METHODS A multi-institutional retrospective review of patients treated for nail unit SCC was performed. Data were collected on patient characteristics, tumor qualities, treatment, and radiographic imaging. A change in treatment was defined as more aggressive treatment (amputation) rather than local excision or Mohs micrographic surgery (MMS). RESULTS One hundred seven patients with nail unit SCC were identified. Approximately 44/107 (41.1%) of patients were imaged and 63/107 (58.9%) were not. Mohs micrographic surgery was the most common primary treatment (66.4%). Mohs micrographic surgery was more commonly performed in nonimaged patients, and amputation was more commonly performed in imaged patients (p less then .001). Bony changes were identified in 13/44 (29.
    Herein, we review the progress in the use of cellular and molecular markers for the accurate identification of PCNs.Metabolic syndrome (MetS) describes a set of risk factors that can eventually lead to the occurrence of cardiovascular and cerebrovascular disease. A detailed understanding of the MetS mechanism will be helpful in developing effective prevention strategies and appropriate intervention tools. In this article, we discuss the relationship between the clinical symptoms of MetS and differences in the gut microbial community compared with healthy individuals, characterized by the proliferation of potentially harmful bacteria and the inhibition of beneficial ones. Interactions between gut microbiota and host metabolism have been shown to be mediated by a number of factors, including inflammation caused by gut barrier defects, short-chain fatty acids metabolism, and bile acid metabolism. However, although we can clearly establish a causal relationship between gut microbial profiles and MetS in animal experiments, the relationship between them is still controversial in humans. Therefore, we need more clinical studies to augment our understanding of how we can manipulate the gut microbiota and address the role of the gut microbiota in the prevention and treatment of MetS.The human gastrointestinal tract accommodates an entire micro-environment for divergent physiologic processes, the dysbiosis of this micro-ecology has a strong inter-action with the pathogenesis of inflammatory bowel disease (IBD). In the past few years, with the advances in the understanding of microbiome, its metabolites and further application of next generation sequencing, analysis of dynamic alteration of gut micro-environment was realized, which provides numerous information beyond simple microbiota structure or metabolites differences under chronic colitis status. The subsequent intervention strategies targeting the modulation of intestinal micro-environment have been explored as a potential therapy. In this review, we will summarize the recent knowledge about multi-dimensional dysbiosis, the inter-action between fungus and bacteria under inflamed mucosa, and the clinical application of probiotics and fecal microbiota transplantation as a promising therapeutic approach in IBD. Type 2 diabetes mellitus (T2DM), a worldwide epidemic, has caused tremendous economic and social burden, but the pathogenesis remains uncertain. Nowadays, the impact of unrhythmic circadian clock caused by irregular sleep and unhealthy diet on T2DM has started to be increasingly studied. https://www.selleckchem.com/products/vanzacaftor.html However, the contribution of the endogenous circadian clock system to the development of T2DM has not yet been satisfactorily explored. It is now becoming clear that the gut microbiota and the circadian clock interact with each other to regulate the host metabolism. Considering all these above, we review the literature related to the gut microbiota, circadian clock, and T2DM to elucidate the idea that the gut microbiota is closely tied to the regulation of the circadian clock in the development of T2DM, which provides potential for gut microbiota-directed therapies to ameliorate the effects of circadian disruptions linked to the occurrence and development of T2DM.Historically, breast cancer has been regarded as an immunogenic "cold" tumor hence it has not experienced the explosion of immunotherapy. However, the discovery of immune checkpoint inhibitors has made immunotherapy becoming an emerging new treatment modality for breast cancer. This review discusses the immune system, immune features of breast cancer, and the programmed cell death protein-1/programmed cell death protein ligand-1 (PD-1/PD-L1) inhibitors used in the treatment of breast cancer. High T lymphocyte infiltration and mutation burden were observed in triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2 (HER2) breast cancer. Increasing breast cancer immunogenicity and modulating the tumor microenvironment has been reported to improve the therapeutic efficacy of immunotherapy. Recent clinical trials involving PD-1/PD-L1 inhibitors monotherapy in breast cancer has revealed little efficacy and this highlights the need to develop combinations of PD-1/PD-L1 inhibitors with chemotherapy, molecularly targeted therapies, and other immunotherapies to maximize the clinical efficacy. In conclusion, the development of a new combined regimen involving PD-1/PD-L1 inhibitors and the exploration as potential biomarkers is important in breast cancer immunotherapy.BACKGROUND Hyperuricemia and gout have become public health concerns; many important guidelines have recommended xanthine oxidase inhibitors (XOIs) as the first-line uric-lowering therapies (ULTs) to treat chronic gout with hyperuricemia. However, whether treating hyperuricemia and gout with ULTs modifies cardiovascular risks remains controversial. The aim of this study was to assess the incident risk of cardiovascular events (CVE) in hyperuricemia population, assess the cardiovascular benefit-risk of ULTs in hyperuricemia patients with or without gout in diverse cardiovascular risk subgroups, and specify the safety of different ULT. METHODS We searched PubMed, Embase, the Cochrane Library, Wanfang, CQVIP, and China National Knowledge Infrastructure (CNKI) Database for prospective cohort studies and randomized controlled trials (RCTs) in English and Chinese. Potential medications included XOIs, and uricosurics. RCTs were divided into subgroups analysis based on blinding status and patients' history of CV dise incidence of cardiovascular events, and the results suggested that XOIs might reduce the incidence of MACE and total CVE. In addition, from the perspective of cardiovascular safety, febuxostat equaled allopurinol in our meta-analysis.BACKGROUND Squamous cell carcinoma (SCC) is the most common malignant tumor of the nail unit. No guidelines currently exist regarding the role of imaging in this specific location. OBJECTIVE To investigate the utility of routine imaging in SCC of the nail apparatus. METHODS A multi-institutional retrospective review of patients treated for nail unit SCC was performed. Data were collected on patient characteristics, tumor qualities, treatment, and radiographic imaging. A change in treatment was defined as more aggressive treatment (amputation) rather than local excision or Mohs micrographic surgery (MMS). RESULTS One hundred seven patients with nail unit SCC were identified. Approximately 44/107 (41.1%) of patients were imaged and 63/107 (58.9%) were not. Mohs micrographic surgery was the most common primary treatment (66.4%). Mohs micrographic surgery was more commonly performed in nonimaged patients, and amputation was more commonly performed in imaged patients (p less then .001). Bony changes were identified in 13/44 (29.
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  • On the other hand, this financial strain was also positively related to students' work hours while in the last semester of college, which was positively related to their odds of securing full-time employment upon graduation. Further mediation tests revealed that only the 3-stage indirect effect through job search strain (i.e., student loan debt → financial strain → job search strain → full-time employment) was statistically significant. The theoretical and practical implications of these findings are discussed. (PsycINFO Database Record (c) 2020 APA, all rights reserved).Although the service-profit chain posits that employees and customers are interrelated at the unit level (Heskett, Sasser, & Schlesinger, 1997), most theory and practice give primary emphasis to the employee. In this study, we sought to draw attention to the relatively neglected influence that customers may collectively have on employees. Specifically, we examined how collective customer perceptions of service quality relate to collective employee job satisfaction, service climate, and collective turnover (voluntary and involuntary). Using a sample of 294 bank branches, 1,975 employees, and 52,920 customers, modeled at the branch level over 2 years, we found that collective customer perceptions of service quality produced a stronger effect on collective employee job satisfaction and service climate than vice versa. We also provided the first tests demonstrating that collective customer perceptions of service quality significantly and independently influence collective voluntary turnover, even while simultaneously modeling collective employee job satisfaction and service climate. Further, we showed that the effects of collective turnover (voluntary and involuntary) are primarily related to collective customer perceptions and service climate, but through different paths. Although the turnover base rates are modest, these empirical findings highlight the role that collective customer perceptions can have in shaping collective employee attitudes, climate, and turnover and, thus, should be considered and replicated in future theory and research. https://www.selleckchem.com/products/cetuximab.html (PsycINFO Database Record (c) 2020 APA, all rights reserved).OBJECTIVE Cognitive models of social anxiety disorder propose that maladaptive safety behaviors (SBs; i.e., behaviors intended to avoid, prevent, or manage threat) play an important maintaining role in the disorder. Though targeting these behaviors for elimination is one component of contemporary cognitive-behavioral therapies for social anxiety, it has rarely been examined as a specific treatment strategy, and, to our knowledge, it has not yet been examined in isolation as an intervention for social anxiety. The current study evaluated an SB reduction intervention for social anxiety that consisted of brief text message reminders. METHOD Individuals with elevated social anxiety (N = 94) were recruited from across the United States and randomized to receive one of two 1-month text message interventions consisting of 16 text message reminders to avoid SBs or focus on the present. Symptoms were assessed at pre- and posttreatment, as well as at 1-month follow-up. RESULTS Both treatments were associated with substantial symptom reduction. Compared to the present-focused text message condition, SB elimination led to lower SB frequency at posttreatment (sr² = .044, p = .048) and lower social anxiety at follow-up (sr² = .096, p = .005). CONCLUSIONS These preliminary findings provide novel evidence for the importance of SBs in social anxiety and suggest text message SB reduction may be an effective, highly accessible intervention for individuals with social anxiety. (PsycINFO Database Record (c) 2020 APA, all rights reserved). TRIAL REGISTRATION ClinicalTrials.gov NCT03562650.OBJECTIVE Suicide ideators and suicide attempters might differ in 3 possible ways. First, they might differ in a simple way such that one or a small set of factors are both necessary and sufficient to distinguish between the 2 groups. Second, ideators and attempters might differ in a complicated way such that a specific combination of a large set of factors is necessary and sufficient for the distinction. Third, complex differences might exist many possible combinations of a large set of factors may be sufficient to distinguish the 2 groups, but no combination may be necessary. This study empirically examined these possibilities. METHOD Across 5 samples (total N = 3,869), univariate logistic regressions were conducted to test for simple differences. To test for complicated and complex differences, machine learning (ML) methods were used to identify the optimized algorithm with all variables. Subsequently, the same methods were repeated after removing the top 5 most important or discriminative variables, and a randomly selected 10% subset of variables. Multiple logistic regressions were conducted with all variables. RESULTS Results were consistent across samples. Univariate logistic regressions on average yielded chance-level accuracy. ML algorithms with all variables showed good accuracy; substantial deviation from the optimized algorithms through the removal of variables did not result in significantly poorer performance. Multiple logistic regressions produced poor to fair accuracy. CONCLUSIONS Differences between suicide ideators and attempters are complex. Findings suggest that their differences may be better understood on a psychological primitive level than a biopsychosocial factor level. (PsycINFO Database Record (c) 2020 APA, all rights reserved).BACKGROUND Air pollution contributes to an estimated six million deaths per year. Epidemiological and experimental studies show an association between air pollutant exposure and respiratory allergy. OBJECTIVE We aimed to write a narrative review of the epidemiology of air pollution-related respiratory-related allergic disorders (including asthma and allergic rhinitis) and the effects of air pollutants - with an emphasis on the particulate matter - on respiratory allergy-related health. METHODS PubMed Medline was searched, and representative epidemiologic and controlled-exposure studies were selected by using terms for air pollutants, particulate matter, and respiratory allergy including asthma and allergic rhinitis. RESULTS Epidemiological studies showed methodologic heterogeneity, including variability in study populations, geographical regions, types and sources of pollutants, methods for exposure estimation, approaches to controlling for confounding, and case definitions. This heterogeneity affected measures of association between studies.
    On the other hand, this financial strain was also positively related to students' work hours while in the last semester of college, which was positively related to their odds of securing full-time employment upon graduation. Further mediation tests revealed that only the 3-stage indirect effect through job search strain (i.e., student loan debt → financial strain → job search strain → full-time employment) was statistically significant. The theoretical and practical implications of these findings are discussed. (PsycINFO Database Record (c) 2020 APA, all rights reserved).Although the service-profit chain posits that employees and customers are interrelated at the unit level (Heskett, Sasser, & Schlesinger, 1997), most theory and practice give primary emphasis to the employee. In this study, we sought to draw attention to the relatively neglected influence that customers may collectively have on employees. Specifically, we examined how collective customer perceptions of service quality relate to collective employee job satisfaction, service climate, and collective turnover (voluntary and involuntary). Using a sample of 294 bank branches, 1,975 employees, and 52,920 customers, modeled at the branch level over 2 years, we found that collective customer perceptions of service quality produced a stronger effect on collective employee job satisfaction and service climate than vice versa. We also provided the first tests demonstrating that collective customer perceptions of service quality significantly and independently influence collective voluntary turnover, even while simultaneously modeling collective employee job satisfaction and service climate. Further, we showed that the effects of collective turnover (voluntary and involuntary) are primarily related to collective customer perceptions and service climate, but through different paths. Although the turnover base rates are modest, these empirical findings highlight the role that collective customer perceptions can have in shaping collective employee attitudes, climate, and turnover and, thus, should be considered and replicated in future theory and research. https://www.selleckchem.com/products/cetuximab.html (PsycINFO Database Record (c) 2020 APA, all rights reserved).OBJECTIVE Cognitive models of social anxiety disorder propose that maladaptive safety behaviors (SBs; i.e., behaviors intended to avoid, prevent, or manage threat) play an important maintaining role in the disorder. Though targeting these behaviors for elimination is one component of contemporary cognitive-behavioral therapies for social anxiety, it has rarely been examined as a specific treatment strategy, and, to our knowledge, it has not yet been examined in isolation as an intervention for social anxiety. The current study evaluated an SB reduction intervention for social anxiety that consisted of brief text message reminders. METHOD Individuals with elevated social anxiety (N = 94) were recruited from across the United States and randomized to receive one of two 1-month text message interventions consisting of 16 text message reminders to avoid SBs or focus on the present. Symptoms were assessed at pre- and posttreatment, as well as at 1-month follow-up. RESULTS Both treatments were associated with substantial symptom reduction. Compared to the present-focused text message condition, SB elimination led to lower SB frequency at posttreatment (sr² = .044, p = .048) and lower social anxiety at follow-up (sr² = .096, p = .005). CONCLUSIONS These preliminary findings provide novel evidence for the importance of SBs in social anxiety and suggest text message SB reduction may be an effective, highly accessible intervention for individuals with social anxiety. (PsycINFO Database Record (c) 2020 APA, all rights reserved). TRIAL REGISTRATION ClinicalTrials.gov NCT03562650.OBJECTIVE Suicide ideators and suicide attempters might differ in 3 possible ways. First, they might differ in a simple way such that one or a small set of factors are both necessary and sufficient to distinguish between the 2 groups. Second, ideators and attempters might differ in a complicated way such that a specific combination of a large set of factors is necessary and sufficient for the distinction. Third, complex differences might exist many possible combinations of a large set of factors may be sufficient to distinguish the 2 groups, but no combination may be necessary. This study empirically examined these possibilities. METHOD Across 5 samples (total N = 3,869), univariate logistic regressions were conducted to test for simple differences. To test for complicated and complex differences, machine learning (ML) methods were used to identify the optimized algorithm with all variables. Subsequently, the same methods were repeated after removing the top 5 most important or discriminative variables, and a randomly selected 10% subset of variables. Multiple logistic regressions were conducted with all variables. RESULTS Results were consistent across samples. Univariate logistic regressions on average yielded chance-level accuracy. ML algorithms with all variables showed good accuracy; substantial deviation from the optimized algorithms through the removal of variables did not result in significantly poorer performance. Multiple logistic regressions produced poor to fair accuracy. CONCLUSIONS Differences between suicide ideators and attempters are complex. Findings suggest that their differences may be better understood on a psychological primitive level than a biopsychosocial factor level. (PsycINFO Database Record (c) 2020 APA, all rights reserved).BACKGROUND Air pollution contributes to an estimated six million deaths per year. Epidemiological and experimental studies show an association between air pollutant exposure and respiratory allergy. OBJECTIVE We aimed to write a narrative review of the epidemiology of air pollution-related respiratory-related allergic disorders (including asthma and allergic rhinitis) and the effects of air pollutants - with an emphasis on the particulate matter - on respiratory allergy-related health. METHODS PubMed Medline was searched, and representative epidemiologic and controlled-exposure studies were selected by using terms for air pollutants, particulate matter, and respiratory allergy including asthma and allergic rhinitis. RESULTS Epidemiological studies showed methodologic heterogeneity, including variability in study populations, geographical regions, types and sources of pollutants, methods for exposure estimation, approaches to controlling for confounding, and case definitions. This heterogeneity affected measures of association between studies.
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  • Distinguishing GBFDE from SJS and TEN is salient and will be stressed GBFDE has more rapid onset in 1-24 h rather than in weeks, less or no mucosal involvement, less or no systemic involvement, and a tendency for a more favorable prognosis; however, recent experience suggests it may be just as life-threatening. This review will provide a comprehensive update and approach to diagnosis and management.BACKGROUND 18F-Flurpiridaz is a promising investigational radiotracer for PET myocardial perfusion imaging with favorable properties for quantification of myocardial blood flow (MBF). We sought to validate the incremental diagnostic value of absolute MBF quantification in a large multicenter trial against quantitative coronary angiography. METHODS We retrospectively analyzed a subset of patients (N = 231) from the first phase 3 flurpiridaz trial (NCT01347710). Dynamic PET data at rest and pharmacologic stress were fit to a previously validated 2-tissue-compartment model. Absolute MBF and myocardial flow reserve (MFR) were compared with coronary artery disease severity quantified by invasive coronary angiography on a per-patient and per-vessel basis. RESULTS Stress MBF per-vessel accurately identified obstructive disease (c-index 0.79) and progressively declined with increasing stenosis severity (2.35 ± 0.71 in patients without ***; 1.92 ± 0.49 in non-obstructed territories of *** patients; and 1.54 ± 0.50 in diseased territories, P  less then  0.05). MFR similarly declined with increasing stenosis severity (3.03 ± 0.94; 2.69 ± 0.95; and 2.33 ± 0.86, respectively, P  less then  0.05). https://www.selleckchem.com/products/odn-1826-sodium.html In multivariable logistic regression modeling, stress MBF and MFR provided incremental diagnostic value beyond patient characteristics and relative perfusion analysis. CONCLUSIONS Clinical myocardial blood flow measurement with 18F-flurpiridaz cardiac PET shows promise for routine application.BACKGROUND The present study was performed to compare the relationship of 18F-fluorodeoxyglucose (FDG) uptake and late gadolinium enhancement (LGE) transmurality with the improvement of left ventricular function in patients with coronary chronic total occlusion (CTO) assessed by hybrid FDG positron emission tomography (PET)/magnetic resonance imaging (MRI). METHODS Thirty-eight consecutive patients with CTO underwent FDG PET/MRI. Twenty-three patients then underwent percutaneous coronary intervention (PCI), and the final study population comprised 15 patients who underwent both initial and follow-up MRI. The degree of wall motion abnormality in each of the 17 myocardial segments was evaluated based on the extent of wall thickening on cine MRI using a 5-point scale. RESULTS Among all 646 myocardial segments at baseline, FDG uptake significantly decreased as the transmurality of LGE is advanced. Of the 15 patients who underwent PCI, 152 segments showed wall motion abnormalities at baseline. The functional recovery of the wall motion abnormality of the PET-viable/MRI-viable segments was highest, and that of the PET-nonviable/MRI-nonviable segments was lowest. There were no differences in functional recovery between the PET-viable/MRI-nonviable and PET-nonviable/MRI-viable segments. CONCLUSION Simultaneous assessment of FDG and LGE using a hybrid PET/MRI system can help to predict functional recovery after PCI in patients with CTO.BACKGROUND Despite the many advantages of recombinant subunit vaccines, they have critical weaknesses that include a low efficacy for promoting cellular and humoral immune responses against antigens because of their poor immunogenicity, and a rapidly cleared properties as a result of proteolytic enzymes in the body. To circumvent these problems, we developed mannan-decorated inulin acetate microparticles (M-IA MPs) that functioned as carriers and adjuvants for immunization with the recombinant foot-and-mouth disease multi-epitope subunit vaccine (M5BT). METHODS The M5BT-loaded M-IA MPs were obtained by a double-emulsion solvent-evaporation method. Their properties including morphology, size and release ability were determined by field emission scanning electron microscope, dynamic light-scattering spectrophotometer and spectrophotometer. To assess the immunization efficacy of the MPs, **** were immunized with MPs and their sera were analyzed by ELISA. RESULTS The M-IA MPs obtained by a double-emulsion solvent-evaporation method were spherical and approximately 2-3 µm, and M5BT was encapsulated in the M-IA MPs. The M5BT-loaded M-IA MPs showed higher antigen-specific IgG, IgG1, IgG2a and anti-FMDV antibodies than the M5BT-loaded IA MPs and the Freund's adjuvant as a control. CONCLUSION The M-IA MPs showed a powerful and multifunctional polymeric system that combined two toll-like receptor agonists compared to the conventional adjuvant.BACKGROUND Gene therapy shows the ability to restore neuronal dysfunction via therapeutic gene expression. The efficiency of gene expression and delivery to hypoxic injury sites is important for successful gene therapy. Therefore, we established a gene/stem cell therapy system using neuron-specific enolase promoter and induced neural stem cells in combination with valproic acid to increase therapeutic gene expression in hypoxic spinal cord injury. METHODS To examine the effect of combined method on enhancing gene expression, we compared neuronal cell-inducible luciferase levels under normoxia or hypoxia conditions in induced neural stem cells with valproic acid. Therapeutic gene, vascular endothelial growth factor, expression with combined method was investigated in hypoxic spinal cord injury model. We verified gene expression levels and the effect of different methods of valproic acid administration in vivo. RESULTS The results showed that neuron-specific enolase promoter enhanced gene expression levels in induced neural stem cells compared to Simian Virus 40 promoter under hypoxic conditions. Valproic acid treatment showed higher gene expression of neuron-specific enolase promoter than without treatment. In addition, gene expression levels and cell viability were different depending on the various concentration of valproic acid. The gene expression levels were increased significantly when valproic acid was directly injected with induced neural stem cells in vivo. CONCLUSION In this study, we demonstrated that the combination of neuron-specific enolase promoter and valproic acid induced gene overexpression in induced neural stem cells under hypoxic conditions and also in spinal cord injury depending on valproic acid administration in vivo. Combination of valproic acid and neuron-specific enolase promoter in induced neural stem cells could be an effective gene therapy system for hypoxic spinal cord injury.
    Distinguishing GBFDE from SJS and TEN is salient and will be stressed GBFDE has more rapid onset in 1-24 h rather than in weeks, less or no mucosal involvement, less or no systemic involvement, and a tendency for a more favorable prognosis; however, recent experience suggests it may be just as life-threatening. This review will provide a comprehensive update and approach to diagnosis and management.BACKGROUND 18F-Flurpiridaz is a promising investigational radiotracer for PET myocardial perfusion imaging with favorable properties for quantification of myocardial blood flow (MBF). We sought to validate the incremental diagnostic value of absolute MBF quantification in a large multicenter trial against quantitative coronary angiography. METHODS We retrospectively analyzed a subset of patients (N = 231) from the first phase 3 flurpiridaz trial (NCT01347710). Dynamic PET data at rest and pharmacologic stress were fit to a previously validated 2-tissue-compartment model. Absolute MBF and myocardial flow reserve (MFR) were compared with coronary artery disease severity quantified by invasive coronary angiography on a per-patient and per-vessel basis. RESULTS Stress MBF per-vessel accurately identified obstructive disease (c-index 0.79) and progressively declined with increasing stenosis severity (2.35 ± 0.71 in patients without CAD; 1.92 ± 0.49 in non-obstructed territories of CAD patients; and 1.54 ± 0.50 in diseased territories, P  less then  0.05). MFR similarly declined with increasing stenosis severity (3.03 ± 0.94; 2.69 ± 0.95; and 2.33 ± 0.86, respectively, P  less then  0.05). https://www.selleckchem.com/products/odn-1826-sodium.html In multivariable logistic regression modeling, stress MBF and MFR provided incremental diagnostic value beyond patient characteristics and relative perfusion analysis. CONCLUSIONS Clinical myocardial blood flow measurement with 18F-flurpiridaz cardiac PET shows promise for routine application.BACKGROUND The present study was performed to compare the relationship of 18F-fluorodeoxyglucose (FDG) uptake and late gadolinium enhancement (LGE) transmurality with the improvement of left ventricular function in patients with coronary chronic total occlusion (CTO) assessed by hybrid FDG positron emission tomography (PET)/magnetic resonance imaging (MRI). METHODS Thirty-eight consecutive patients with CTO underwent FDG PET/MRI. Twenty-three patients then underwent percutaneous coronary intervention (PCI), and the final study population comprised 15 patients who underwent both initial and follow-up MRI. The degree of wall motion abnormality in each of the 17 myocardial segments was evaluated based on the extent of wall thickening on cine MRI using a 5-point scale. RESULTS Among all 646 myocardial segments at baseline, FDG uptake significantly decreased as the transmurality of LGE is advanced. Of the 15 patients who underwent PCI, 152 segments showed wall motion abnormalities at baseline. The functional recovery of the wall motion abnormality of the PET-viable/MRI-viable segments was highest, and that of the PET-nonviable/MRI-nonviable segments was lowest. There were no differences in functional recovery between the PET-viable/MRI-nonviable and PET-nonviable/MRI-viable segments. CONCLUSION Simultaneous assessment of FDG and LGE using a hybrid PET/MRI system can help to predict functional recovery after PCI in patients with CTO.BACKGROUND Despite the many advantages of recombinant subunit vaccines, they have critical weaknesses that include a low efficacy for promoting cellular and humoral immune responses against antigens because of their poor immunogenicity, and a rapidly cleared properties as a result of proteolytic enzymes in the body. To circumvent these problems, we developed mannan-decorated inulin acetate microparticles (M-IA MPs) that functioned as carriers and adjuvants for immunization with the recombinant foot-and-mouth disease multi-epitope subunit vaccine (M5BT). METHODS The M5BT-loaded M-IA MPs were obtained by a double-emulsion solvent-evaporation method. Their properties including morphology, size and release ability were determined by field emission scanning electron microscope, dynamic light-scattering spectrophotometer and spectrophotometer. To assess the immunization efficacy of the MPs, mice were immunized with MPs and their sera were analyzed by ELISA. RESULTS The M-IA MPs obtained by a double-emulsion solvent-evaporation method were spherical and approximately 2-3 µm, and M5BT was encapsulated in the M-IA MPs. The M5BT-loaded M-IA MPs showed higher antigen-specific IgG, IgG1, IgG2a and anti-FMDV antibodies than the M5BT-loaded IA MPs and the Freund's adjuvant as a control. CONCLUSION The M-IA MPs showed a powerful and multifunctional polymeric system that combined two toll-like receptor agonists compared to the conventional adjuvant.BACKGROUND Gene therapy shows the ability to restore neuronal dysfunction via therapeutic gene expression. The efficiency of gene expression and delivery to hypoxic injury sites is important for successful gene therapy. Therefore, we established a gene/stem cell therapy system using neuron-specific enolase promoter and induced neural stem cells in combination with valproic acid to increase therapeutic gene expression in hypoxic spinal cord injury. METHODS To examine the effect of combined method on enhancing gene expression, we compared neuronal cell-inducible luciferase levels under normoxia or hypoxia conditions in induced neural stem cells with valproic acid. Therapeutic gene, vascular endothelial growth factor, expression with combined method was investigated in hypoxic spinal cord injury model. We verified gene expression levels and the effect of different methods of valproic acid administration in vivo. RESULTS The results showed that neuron-specific enolase promoter enhanced gene expression levels in induced neural stem cells compared to Simian Virus 40 promoter under hypoxic conditions. Valproic acid treatment showed higher gene expression of neuron-specific enolase promoter than without treatment. In addition, gene expression levels and cell viability were different depending on the various concentration of valproic acid. The gene expression levels were increased significantly when valproic acid was directly injected with induced neural stem cells in vivo. CONCLUSION In this study, we demonstrated that the combination of neuron-specific enolase promoter and valproic acid induced gene overexpression in induced neural stem cells under hypoxic conditions and also in spinal cord injury depending on valproic acid administration in vivo. Combination of valproic acid and neuron-specific enolase promoter in induced neural stem cells could be an effective gene therapy system for hypoxic spinal cord injury.
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