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9 المنشورات
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0 الصور
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0 الفيديوهات
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Male
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20/07/1981
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متابَع بواسطة 0 أشخاص
التحديثات الأخيرة
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Z depend on sex and the type of task, and are influenced by history of stress. These data suggest that H2A.Z may be a sex-specific epigenetic risk factor for PTSD susceptibility, with implications for developing sex-specific therapeutic interventions.Increased adoption of improved agricultural technologies is considered an essential step to address global poverty and hunger, and agronomic trials suggest intensification in developing countries could result in large yield gains. Yet the promise of new technologies does not always carry over from trials to real-life conditions, and diffusion of many technologies remains limited. We show how parcel and farmer selection, together with behavioural responses in agronomic trials, can explain why yield gain estimates from trials may differ from the yield gains of smallholders using the same inputs under real-life conditions. We provide quantitative evidence by exploiting variation in farmer selection and detailed data collection from research trials in Western Kenya on which large yield increments were observed from improved input packages for maize and soybean. After adjusting for selection, behavioural responses, and other corrections, estimates of yield gains fall to being not significantly different from zero for the input package tested on one of the crops (soybean), but remain high for the other (maize). These results suggest that testing new agricultural technologies in real-world conditions and without researcher interference early in the agricultural research and development process might help with identifying which innovations are more likely to be taken up at scale.We study the performance of an electromechanical harmonic oscillator chain as an energy harvester to extract power from finite-bandwidth ambient random vibrations, which are modelled by colored noise. The proposed device is numerically simulated and its performance assessed by means of the net electrical power generated and its efficiency in converting the external noise-supplied power into electrical power. Our main result is a **** enhanced performance, both in the net electrical power delivered and in efficiency, of the harmonic chain with respect to the popular single oscillator resonator. Our numerical findings are explained by means of an analytical approximation, in excellent agreement with numerics.We consider asymmetric and symmetric dimerized two-leg ladders, comprising of four different lattice points per unit cell, illuminated by circularly polarized light. In the asymmetric dimerized ladder case, rungs are not perpendicular to the ladder's legs whereas the rungs are perpendicular to the legs for the symmetric one. Using the Floquet theory, we obtain an effective Hamiltonian to study topological properties of the systems. Depending on the dimerization strength and driving amplitude, it is shown that topologically protected edge states manifest themselves not only as a zero-energy band within the gap between conduction and valence band but also as finite-energy curved bands inside the gap of subbands. The latter one can penetrate into bulk states and hybridize with the bulk states revealing hybridized Floquet topological metal phase with delocalized edge states in the asymmetric ladder case. However, in the symmetric ladder, the finite-energy edge states while remaining localized can coexist with the extended bulk states manifesting Floquet topological metal phase.Plant-pathogen interactions follow spatial and temporal developmental dynamics where gene expression in pathogen and host undergo crucial changes. Therefore, it is of great interest to detect, quantify and localise where and when key genes are active to understand these processes. Many pathosystems are not accessible for genetic amendments or other spatially-resolved gene expression monitoring methods. Here, we adapt single molecule FISH techniques to demonstrate the presence and activity of mRNAs at the single-cell level using phytomyxids in their plant and algal host in lab and field material. This allowed us to monitor and quantify the expression of genes from the clubroot pathogen Plasmodiophora brassicae, several species of its Brassica hosts, and of several brown algae, including the genome model Ectocarpus siliculosus, infected with the phytomyxid Maullinia ectocarpii. We show that mRNAs are localised along a spatiotemporal gradient, thus providing a proof-of-concept of the usefulness of single-molecule FISH to increase knowledge about the interactions between plants, algae and phytomyxids. The methods used are easily applicable to any interaction between microbes and their algal or plant host, and have therefore the potential to rapidly increase our understanding of key, spatially- and temporally-resolved processes underpinning complex plant-microbe interactions.Rivers around the world are threatened by altered flow due to water resource development. Altered flow can change food webs and impact riverine energetics. The Fitzroy River, in northern Australia, is targeted for development but uncertainty remains about the sources of carbon supporting the food web, particularly in the lowlands-the region most likely to be impacted by water extraction. This study used stable isotopes to investigate if algal biofilm is the main carbon source sustaining fish in lowland habitats. We also sought evidence that large-bodied migratory fish were transporting remote carbon around the system. Our results revealed that local algal biofilm carbon was the dominant source of energy sustaining fish in wet season floodplain habitats, but that fish in main-channel pools during the dry season were increasingly dependent on other carbon sources, such as leaf litter or phytoplankton. We found no evidence that large-bodied fish were transporting remote carbon from the floodplain or estuary into the lower main-channel of the river. We recommend that water planners take a precautionary approach to policy until sufficient food web evidence is amassed.Worldwide demand for tef (Eragrostis tef) as a functional food for human consumption is increasing, thanks to its nutritional benefits and gluten-free properties. https://www.selleckchem.com/products/cpi-455.html As a result, tef in now grown outside its native environment in Ethiopia and thus information is required regarding plant nutrition demands in these areas, as well as resulting grain health-related composition. In the current work, two tef genotypes were grown in Israel under irrigation in two platforms, plots in the field and pots in a greenhouse, with four and five nitrogen treatments, respectively. Nutritional and health-related quality traits were analyzed, including mineral content, fatty acid composition, hydrophilic and lipophilic antioxidative capacity, total phenolic content and basic polyphenolic profile. Our results show that tef genotypes differ in their nutritional composition, e.g. higher phenolic contents in the brown compared to the white genotype. Additionally, nitrogen availability positively affected grain fatty acid composition and iron levels in both experiments, while negatively affecting total phenolics in the field trials.
Z depend on sex and the type of task, and are influenced by history of stress. These data suggest that H2A.Z may be a sex-specific epigenetic risk factor for PTSD susceptibility, with implications for developing sex-specific therapeutic interventions.Increased adoption of improved agricultural technologies is considered an essential step to address global poverty and hunger, and agronomic trials suggest intensification in developing countries could result in large yield gains. Yet the promise of new technologies does not always carry over from trials to real-life conditions, and diffusion of many technologies remains limited. We show how parcel and farmer selection, together with behavioural responses in agronomic trials, can explain why yield gain estimates from trials may differ from the yield gains of smallholders using the same inputs under real-life conditions. We provide quantitative evidence by exploiting variation in farmer selection and detailed data collection from research trials in Western Kenya on which large yield increments were observed from improved input packages for maize and soybean. After adjusting for selection, behavioural responses, and other corrections, estimates of yield gains fall to being not significantly different from zero for the input package tested on one of the crops (soybean), but remain high for the other (maize). These results suggest that testing new agricultural technologies in real-world conditions and without researcher interference early in the agricultural research and development process might help with identifying which innovations are more likely to be taken up at scale.We study the performance of an electromechanical harmonic oscillator chain as an energy harvester to extract power from finite-bandwidth ambient random vibrations, which are modelled by colored noise. The proposed device is numerically simulated and its performance assessed by means of the net electrical power generated and its efficiency in converting the external noise-supplied power into electrical power. Our main result is a much enhanced performance, both in the net electrical power delivered and in efficiency, of the harmonic chain with respect to the popular single oscillator resonator. Our numerical findings are explained by means of an analytical approximation, in excellent agreement with numerics.We consider asymmetric and symmetric dimerized two-leg ladders, comprising of four different lattice points per unit cell, illuminated by circularly polarized light. In the asymmetric dimerized ladder case, rungs are not perpendicular to the ladder's legs whereas the rungs are perpendicular to the legs for the symmetric one. Using the Floquet theory, we obtain an effective Hamiltonian to study topological properties of the systems. Depending on the dimerization strength and driving amplitude, it is shown that topologically protected edge states manifest themselves not only as a zero-energy band within the gap between conduction and valence band but also as finite-energy curved bands inside the gap of subbands. The latter one can penetrate into bulk states and hybridize with the bulk states revealing hybridized Floquet topological metal phase with delocalized edge states in the asymmetric ladder case. However, in the symmetric ladder, the finite-energy edge states while remaining localized can coexist with the extended bulk states manifesting Floquet topological metal phase.Plant-pathogen interactions follow spatial and temporal developmental dynamics where gene expression in pathogen and host undergo crucial changes. Therefore, it is of great interest to detect, quantify and localise where and when key genes are active to understand these processes. Many pathosystems are not accessible for genetic amendments or other spatially-resolved gene expression monitoring methods. Here, we adapt single molecule FISH techniques to demonstrate the presence and activity of mRNAs at the single-cell level using phytomyxids in their plant and algal host in lab and field material. This allowed us to monitor and quantify the expression of genes from the clubroot pathogen Plasmodiophora brassicae, several species of its Brassica hosts, and of several brown algae, including the genome model Ectocarpus siliculosus, infected with the phytomyxid Maullinia ectocarpii. We show that mRNAs are localised along a spatiotemporal gradient, thus providing a proof-of-concept of the usefulness of single-molecule FISH to increase knowledge about the interactions between plants, algae and phytomyxids. The methods used are easily applicable to any interaction between microbes and their algal or plant host, and have therefore the potential to rapidly increase our understanding of key, spatially- and temporally-resolved processes underpinning complex plant-microbe interactions.Rivers around the world are threatened by altered flow due to water resource development. Altered flow can change food webs and impact riverine energetics. The Fitzroy River, in northern Australia, is targeted for development but uncertainty remains about the sources of carbon supporting the food web, particularly in the lowlands-the region most likely to be impacted by water extraction. This study used stable isotopes to investigate if algal biofilm is the main carbon source sustaining fish in lowland habitats. We also sought evidence that large-bodied migratory fish were transporting remote carbon around the system. Our results revealed that local algal biofilm carbon was the dominant source of energy sustaining fish in wet season floodplain habitats, but that fish in main-channel pools during the dry season were increasingly dependent on other carbon sources, such as leaf litter or phytoplankton. We found no evidence that large-bodied fish were transporting remote carbon from the floodplain or estuary into the lower main-channel of the river. We recommend that water planners take a precautionary approach to policy until sufficient food web evidence is amassed.Worldwide demand for tef (Eragrostis tef) as a functional food for human consumption is increasing, thanks to its nutritional benefits and gluten-free properties. https://www.selleckchem.com/products/cpi-455.html As a result, tef in now grown outside its native environment in Ethiopia and thus information is required regarding plant nutrition demands in these areas, as well as resulting grain health-related composition. In the current work, two tef genotypes were grown in Israel under irrigation in two platforms, plots in the field and pots in a greenhouse, with four and five nitrogen treatments, respectively. Nutritional and health-related quality traits were analyzed, including mineral content, fatty acid composition, hydrophilic and lipophilic antioxidative capacity, total phenolic content and basic polyphenolic profile. Our results show that tef genotypes differ in their nutritional composition, e.g. higher phenolic contents in the brown compared to the white genotype. Additionally, nitrogen availability positively affected grain fatty acid composition and iron levels in both experiments, while negatively affecting total phenolics in the field trials.0 التعليقات 0 المشاركات 26 مشاهدة 0 معاينةالرجاء تسجيل الدخول , للأعجاب والمشاركة والتعليق على هذا! -
OBJECTIVES The study explored job stress, burnout, work-life balance, well-being, and job satisfaction among pathology residents and fellows. The aims were to examine the prevalence and sources of stress and burnout, as well as identify resources to promote work-life balance and well-being and prevent burnout. METHODS The study used a cross-sectional survey deployed online to a large national sample of pathology residents and fellows. RESULTS Job stress and burnout were prevalent, with more than a third of the respondents reporting that they were currently experiencing burnout. The respondents, particularly residents, were struggling with academics, and higher percentages were struggling with work-life balance and emotional well-being. Overall, the majority of respondents who rated their work-life balance indicated that it was poor or fair. Among the factors contributing to job stress and burnout and detracting from work-life balance, workload was the leading factor. CONCLUSIONS The factors contributing to job stress and burnout included organizational factors such as workload, value, and aspects of the learning environment, as well as personal factors such as work-life integration. One of the overarching implications is the need to address a range of interdependent considerations in designing resources to reduce job stress, promote work-life balance, and prevent burnout. © American Society for Clinical Pathology, 2020. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.AIM The human papilloma virus has been associated with anal, cervical, vaginal, and penile cancers. The primary aim of this population-based study is to determine whether HPV-associated cancers are more commonplace in patients with inflammatory bowel disease (IBD). METHOD The Hospital Episode Statistics (HES) database from 1997 to 2012, linked with officer for age standardized rates (ASR), were calculated using population data, and Cox regression analysis was used to determine whether IBD patients have poorer survival compared with non-IBD patients. RESULTS A total of 61,648 patients were included in this study; of these, 837 patients had a preexisting diagnosis of IBD (1.4%). Inflammatory bowel disease patients had a significantly higher ASR of anal cancers than the non-IBD population 5.5 per 100,000 in the IBD group compared with 1.8 in the non-IBD group. The IBD group was also diagnosed with anal cancers at a younger age (60 years compared with 66 years in the non-IBD group, P less then 0.001). The survival of IBD patients with anal cancer was also poorer than the non-IBD group (hazard ratio, 1.32; 95% confidence interval, 1.15-1.52; P less then 0.001). On average, survival was significantly shorter in the IBD group with anal cancer (46 months) compared with the non-IBD group (61 months, P less then 0.001). Age standardized rates for cervical cancer was significantly higher in the IBD group (5.2 of 100,000) compared with the non-IBD group (4.6 of 100,000 P = 0.042). CONCLUSION Patients with IBD have a higher rate of anal cancer compared with the general population. Survival is also worse for anal cancers in the IBD group. © 2020 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. https://www.selleckchem.com/products/cpi-455.html For permissions, please e-mail journals.permissions@oup.com.BACKGROUND AND AIMS Gadolinium-enhanced sequences are not included in the simplified Magnetic Resonance Index of Activity (sMARIA), but in the derivation of this index readers had access to these sequences. The current study aimed to validate the sMARIA without gadolinium-enhanced sequences for assessing disease activity, severity, and response to treatment in patients with Crohn's disease. PATIENTS AND METHODS We prospectively included patients with active Crohn's disease and at least one segment with severe inflammation (ulcers) at ileocolonoscopy who required treatment with biological drugs. Patients were evaluated by both MRE and ileocolonoscopy at baseline and 46 weeks after initiation of medical treatment. We compared the quantification of disease activity and response to treatment with sMARIA versus with ileocolonoscopy (CDEIS), considered the gold standard. RESULTS Data from both MRE and ileocolonoscopy 46 weeks after treatment initiation were available for 39 of the 50 patients. As in the derivation study, the optimal cutoffs were sMARIA≥1 for predicting active disease (area under the curve [AUC] 0.92) and sMARIA≥2 for predicting the presence of ulcers at ileocolonoscopy (AUC 0.93). In evaluating the response to treatment, the sMARIA detected endoscopic ulcer healing at the segment level (sMARIA less then 2) with 89.5% sensitivity and 87.5% specificity. The sMARIA decreased significantly (p less then 0.001) in segments achieving endoscopic ulcer healing, but did not change (p=0.222) in segments with persistent ulceration. © The Author(s) 2020. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email journals.permissions@oup.com.Importance Several randomized clinical trials have recently established the safety and efficacy of endovascular treatment (EVT) of acute ischemic stroke in the anterior circulation. However, it remains uncertain whether patients with acute basilar artery occlusion (BAO) benefit from EVT. Objective To evaluate the association between EVT and clinical outcomes of patients with acute BAO. Design, Setting, and Participants This nonrandomized cohort study, the EVT for Acute Basilar Artery Occlusion Study (BASILAR) study, was a nationwide prospective registry of consecutive patients presenting with an acute, symptomatic, radiologically confirmed BAO to 47 comprehensive stroke centers across 15 provinces in China between January 2014 and May 2019. Patients with acute BAO within 24 hours of estimated occlusion time were divided into groups receiving standard medical treatment plus EVT or standard medical treatment alone. Main Outcomes and Measures The primary outcome was the improvement in modified Rankin Scale scorele scores of 3 or less (adjusted odds ratio, 4.70 [95% CI, 2.53-8.75]; P less then .001) and a lower rate of 90-day mortality (adjusted odds ratio, 2.93 [95% CI, 1.95-4.40]; P less then .001) despite an increase in symptomatic intracerebral hemorrhage (45 of 636 patients [7.1%] vs 1 of 182 patients [0.5%]; P less then .001). Conclusions and Relevance Among patients with acute BAO, EVT administered within 24 hours of estimated occlusion time is associated with better functional outcomes and reduced mortality.
OBJECTIVES The study explored job stress, burnout, work-life balance, well-being, and job satisfaction among pathology residents and fellows. The aims were to examine the prevalence and sources of stress and burnout, as well as identify resources to promote work-life balance and well-being and prevent burnout. METHODS The study used a cross-sectional survey deployed online to a large national sample of pathology residents and fellows. RESULTS Job stress and burnout were prevalent, with more than a third of the respondents reporting that they were currently experiencing burnout. The respondents, particularly residents, were struggling with academics, and higher percentages were struggling with work-life balance and emotional well-being. Overall, the majority of respondents who rated their work-life balance indicated that it was poor or fair. Among the factors contributing to job stress and burnout and detracting from work-life balance, workload was the leading factor. CONCLUSIONS The factors contributing to job stress and burnout included organizational factors such as workload, value, and aspects of the learning environment, as well as personal factors such as work-life integration. One of the overarching implications is the need to address a range of interdependent considerations in designing resources to reduce job stress, promote work-life balance, and prevent burnout. © American Society for Clinical Pathology, 2020. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.AIM The human papilloma virus has been associated with anal, cervical, vaginal, and penile cancers. The primary aim of this population-based study is to determine whether HPV-associated cancers are more commonplace in patients with inflammatory bowel disease (IBD). METHOD The Hospital Episode Statistics (HES) database from 1997 to 2012, linked with officer for age standardized rates (ASR), were calculated using population data, and Cox regression analysis was used to determine whether IBD patients have poorer survival compared with non-IBD patients. RESULTS A total of 61,648 patients were included in this study; of these, 837 patients had a preexisting diagnosis of IBD (1.4%). Inflammatory bowel disease patients had a significantly higher ASR of anal cancers than the non-IBD population 5.5 per 100,000 in the IBD group compared with 1.8 in the non-IBD group. The IBD group was also diagnosed with anal cancers at a younger age (60 years compared with 66 years in the non-IBD group, P less then 0.001). The survival of IBD patients with anal cancer was also poorer than the non-IBD group (hazard ratio, 1.32; 95% confidence interval, 1.15-1.52; P less then 0.001). On average, survival was significantly shorter in the IBD group with anal cancer (46 months) compared with the non-IBD group (61 months, P less then 0.001). Age standardized rates for cervical cancer was significantly higher in the IBD group (5.2 of 100,000) compared with the non-IBD group (4.6 of 100,000 P = 0.042). CONCLUSION Patients with IBD have a higher rate of anal cancer compared with the general population. Survival is also worse for anal cancers in the IBD group. © 2020 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. https://www.selleckchem.com/products/cpi-455.html For permissions, please e-mail journals.permissions@oup.com.BACKGROUND AND AIMS Gadolinium-enhanced sequences are not included in the simplified Magnetic Resonance Index of Activity (sMARIA), but in the derivation of this index readers had access to these sequences. The current study aimed to validate the sMARIA without gadolinium-enhanced sequences for assessing disease activity, severity, and response to treatment in patients with Crohn's disease. PATIENTS AND METHODS We prospectively included patients with active Crohn's disease and at least one segment with severe inflammation (ulcers) at ileocolonoscopy who required treatment with biological drugs. Patients were evaluated by both MRE and ileocolonoscopy at baseline and 46 weeks after initiation of medical treatment. We compared the quantification of disease activity and response to treatment with sMARIA versus with ileocolonoscopy (CDEIS), considered the gold standard. RESULTS Data from both MRE and ileocolonoscopy 46 weeks after treatment initiation were available for 39 of the 50 patients. As in the derivation study, the optimal cutoffs were sMARIA≥1 for predicting active disease (area under the curve [AUC] 0.92) and sMARIA≥2 for predicting the presence of ulcers at ileocolonoscopy (AUC 0.93). In evaluating the response to treatment, the sMARIA detected endoscopic ulcer healing at the segment level (sMARIA less then 2) with 89.5% sensitivity and 87.5% specificity. The sMARIA decreased significantly (p less then 0.001) in segments achieving endoscopic ulcer healing, but did not change (p=0.222) in segments with persistent ulceration. © The Author(s) 2020. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email journals.permissions@oup.com.Importance Several randomized clinical trials have recently established the safety and efficacy of endovascular treatment (EVT) of acute ischemic stroke in the anterior circulation. However, it remains uncertain whether patients with acute basilar artery occlusion (BAO) benefit from EVT. Objective To evaluate the association between EVT and clinical outcomes of patients with acute BAO. Design, Setting, and Participants This nonrandomized cohort study, the EVT for Acute Basilar Artery Occlusion Study (BASILAR) study, was a nationwide prospective registry of consecutive patients presenting with an acute, symptomatic, radiologically confirmed BAO to 47 comprehensive stroke centers across 15 provinces in China between January 2014 and May 2019. Patients with acute BAO within 24 hours of estimated occlusion time were divided into groups receiving standard medical treatment plus EVT or standard medical treatment alone. Main Outcomes and Measures The primary outcome was the improvement in modified Rankin Scale scorele scores of 3 or less (adjusted odds ratio, 4.70 [95% CI, 2.53-8.75]; P less then .001) and a lower rate of 90-day mortality (adjusted odds ratio, 2.93 [95% CI, 1.95-4.40]; P less then .001) despite an increase in symptomatic intracerebral hemorrhage (45 of 636 patients [7.1%] vs 1 of 182 patients [0.5%]; P less then .001). Conclusions and Relevance Among patients with acute BAO, EVT administered within 24 hours of estimated occlusion time is associated with better functional outcomes and reduced mortality.0 التعليقات 0 المشاركات 24 مشاهدة 0 معاينة -
In the past five years, droplet microfluidic techniques have unlocked new opportunities for the high-throughput genome-wide analysis of single cells, transforming our understanding of cellular diversity and function. However, the field lacks an accessible method to screen and sort droplets based on cellular phenotype upstream of genetic analysis, particularly for large and complex cells. To meet this need, we developed Dropception, a robust, easy-to-use workflow for precise single-cell encapsulation into picoliter-scale double emulsion droplets compatible with high-throughput screening via fluorescence-activated cell sorting (FACS). We demonstrate the capabilities of this method by encapsulating five standardized mammalian cell lines of varying sizes and morphologies as well as a heterogeneous cell mixture of a whole dissociated flatworm (5-25 μm in diameter) within highly monodisperse double emulsions (35 μm in diameter). We optimize for preferential encapsulation of single cells with extremely low multiple-cell loading events ( less then 2% of cell-containing droplets), thereby allowing direct linkage of cellular phenotype to genotype. Across all cell lines, cell loading efficiency approaches the theoretical limit with no observable bias by cell size. FACS measurements reveal the ability to discriminate empty droplets from those containing cells with good agreement to single-cell occupancies quantified via microscopy, establishing robust droplet screening at single-cell resolution. High-throughput FACS screening of cellular picoreactors has the potential to shift the landscape of single-cell droplet microfluidics by expanding the repertoire of current nucleic acid droplet assays to include functional phenotyping.Growing antimicrobial resistance (AMR) is a serious global threat to human health. Current methods to detect resistance include phenotypic antibiotic sensitivity testing (AST), which measures bacterial growth and is therefore hampered by a slow time to obtain results (∼12-24 h). Therefore, new rapid phenotypic methods for AST are urgently needed. Nanomechanical cantilever sensors have recently shown promise for rapid AST but challenges of bacterial immobilization can lead to variable results. Herein, a novel cantilever-based method is described for detecting phenotypic antibiotic resistance within ∼45 min, capable of detecting single bacteria. This method does not require complex, variable bacterial immobilization and instead uses a laser and detector system to detect single bacterial cells in media as they pass through the laser focus. This provides a simple readout of bacterial antibiotic resistance by detecting growth (resistant) or death (sensitive), **** faster than the current methods. The potential of this technique is demonstrated by determining the resistance in both laboratory and clinical strains of Escherichia coli (E. https://www.selleckchem.com/products/bms-345541.html coli), a key species responsible for clinically burdensome urinary tract infections. This work provides the basis for a simple and fast diagnostic tool to detect antibiotic resistance in bacteria, reducing the health and economic burdens of AMR.In this work, a unique comprehensive and comparative analysis of photoinduced charge generation, recombination kinetics, and energy losses has been carried out to study the effect of different fullerene-based acceptors (FBAs) and nonfullerene acceptors (NFAs) on the performance of organic solar cells (OSCs). For this, different FBAs, specifically ICBA, PC60BM, and PC70BM, and NFAs, namely, ITIC, IT-4F, and IEICO-4F, were employed independently along with a particular donor polymer, PBDB-T, to fabricate bulk heterojunction OSCs and their performances have been compared. This donor molecule is known to give similar power conversion efficiency (PCE) with FBAs and NFAs and hence is ideal for comparative studies. The origin of the higher PCE of NFA-based OSCs vs FBA-based OSCs is analyzed in terms of spectral coverage, charge generation, recombination, and energy loss. It is found that the energy loss (ΔEloss) is ∼0.8 to 1 eV for FBA-based OSCs, while it is 0.5-0.7 eV for NFA-based OSCs. Interestingly, for the PBDB-TIEICO-4F-based system, energy losses due to charge generation (ΔECT) are ∼0 eV and therefore this system has minimum ΔEloss among all of the studied devices. Providing a systematic, comprehensive, and comparative outlook, our study may further be extended to new upcoming NFA systems and beyond the donor system used in this work.Fluorescence methods are important tools to identify RNA-binding small molecules and further employed to study RNA-protein interactions. Most reported fluorescence strategies are based on covalent labeling of ligand or RNA, which can impede the binding between them to some extent, or light-off fluorescent indicator displacement methods, which ask for particular indicators. Herein, a label-free fluorescence strategy based on the light-on aggregation-induced emission (AIE) feature of tetraphenylethene (TPE) derivative to screen RNA-binding small molecules is presented. As a result of electrostatic interaction, the selected peptides can induce self-assembly of the TPE derivative to produce strong fluorescent emission; when the peptides are bound to RNA molecules, the TPE derivative is in the deaggregated form and shows no or minimum fluorescence. Based on the phenomenon, a competitive displacement assay combined with the TPE reporter was employed to characterize selected small molecules for their binding abilities to HIV-I RNAs. This AIE feature enables the fluorescence-off state of the TPE derivative in the presence of RNA-peptide complex to be "lightened up" quickly as the RNA-binding molecule is introduced and the peptide is competitively released. This strategy was carried out to test several small molecule binders, and the results are consistent with previous reports. This report gives an inspiring example of AIE-based fluorescent assay for HIV-I RNA-binding molecule screening, which may further be explored to build a drug screening platform for RNA-protein interference.Drug-induced hepatic damage has drawn great attention on public health problems. Drugs are biotransformed in the liver by enzymatic processes, accompanied by the production of reactive free radicals, which is the main cause of drug-induced hepatotoxicity. However, the limited penetration of optics makes the use of current luminescence imaging more difficult for acquiring free radicals mapping for lesion location, when applied to whole-body imaging in vivo. In this work, we develop an activatable nanoprobe based on Prussian blue (PB) that can combine magnetic resonance imaging (MRI) and photoacoustic imaging (PAI) for deep-tissue ONOO- imaging. We discover that ONOO- can oxidize FeII within PB into FeIII and meanwhile destroy the crystal structure of PB so that the strong absorption of PB at 710 nm that originated from the electron transferring between FeII and FeIII is greatly diminished. As a result, the reduced photoacoustic imaging (PA) signal of PB is able to function as an indicator for sensing ONOO-. Importantly, after reaction with ONOO-, the reduced size of PB results in the decrease of rotational correlation time (τR), leading to the activatable MRI signal for sensing ONOO-.
In the past five years, droplet microfluidic techniques have unlocked new opportunities for the high-throughput genome-wide analysis of single cells, transforming our understanding of cellular diversity and function. However, the field lacks an accessible method to screen and sort droplets based on cellular phenotype upstream of genetic analysis, particularly for large and complex cells. To meet this need, we developed Dropception, a robust, easy-to-use workflow for precise single-cell encapsulation into picoliter-scale double emulsion droplets compatible with high-throughput screening via fluorescence-activated cell sorting (FACS). We demonstrate the capabilities of this method by encapsulating five standardized mammalian cell lines of varying sizes and morphologies as well as a heterogeneous cell mixture of a whole dissociated flatworm (5-25 μm in diameter) within highly monodisperse double emulsions (35 μm in diameter). We optimize for preferential encapsulation of single cells with extremely low multiple-cell loading events ( less then 2% of cell-containing droplets), thereby allowing direct linkage of cellular phenotype to genotype. Across all cell lines, cell loading efficiency approaches the theoretical limit with no observable bias by cell size. FACS measurements reveal the ability to discriminate empty droplets from those containing cells with good agreement to single-cell occupancies quantified via microscopy, establishing robust droplet screening at single-cell resolution. High-throughput FACS screening of cellular picoreactors has the potential to shift the landscape of single-cell droplet microfluidics by expanding the repertoire of current nucleic acid droplet assays to include functional phenotyping.Growing antimicrobial resistance (AMR) is a serious global threat to human health. Current methods to detect resistance include phenotypic antibiotic sensitivity testing (AST), which measures bacterial growth and is therefore hampered by a slow time to obtain results (∼12-24 h). Therefore, new rapid phenotypic methods for AST are urgently needed. Nanomechanical cantilever sensors have recently shown promise for rapid AST but challenges of bacterial immobilization can lead to variable results. Herein, a novel cantilever-based method is described for detecting phenotypic antibiotic resistance within ∼45 min, capable of detecting single bacteria. This method does not require complex, variable bacterial immobilization and instead uses a laser and detector system to detect single bacterial cells in media as they pass through the laser focus. This provides a simple readout of bacterial antibiotic resistance by detecting growth (resistant) or death (sensitive), much faster than the current methods. The potential of this technique is demonstrated by determining the resistance in both laboratory and clinical strains of Escherichia coli (E. https://www.selleckchem.com/products/bms-345541.html coli), a key species responsible for clinically burdensome urinary tract infections. This work provides the basis for a simple and fast diagnostic tool to detect antibiotic resistance in bacteria, reducing the health and economic burdens of AMR.In this work, a unique comprehensive and comparative analysis of photoinduced charge generation, recombination kinetics, and energy losses has been carried out to study the effect of different fullerene-based acceptors (FBAs) and nonfullerene acceptors (NFAs) on the performance of organic solar cells (OSCs). For this, different FBAs, specifically ICBA, PC60BM, and PC70BM, and NFAs, namely, ITIC, IT-4F, and IEICO-4F, were employed independently along with a particular donor polymer, PBDB-T, to fabricate bulk heterojunction OSCs and their performances have been compared. This donor molecule is known to give similar power conversion efficiency (PCE) with FBAs and NFAs and hence is ideal for comparative studies. The origin of the higher PCE of NFA-based OSCs vs FBA-based OSCs is analyzed in terms of spectral coverage, charge generation, recombination, and energy loss. It is found that the energy loss (ΔEloss) is ∼0.8 to 1 eV for FBA-based OSCs, while it is 0.5-0.7 eV for NFA-based OSCs. Interestingly, for the PBDB-TIEICO-4F-based system, energy losses due to charge generation (ΔECT) are ∼0 eV and therefore this system has minimum ΔEloss among all of the studied devices. Providing a systematic, comprehensive, and comparative outlook, our study may further be extended to new upcoming NFA systems and beyond the donor system used in this work.Fluorescence methods are important tools to identify RNA-binding small molecules and further employed to study RNA-protein interactions. Most reported fluorescence strategies are based on covalent labeling of ligand or RNA, which can impede the binding between them to some extent, or light-off fluorescent indicator displacement methods, which ask for particular indicators. Herein, a label-free fluorescence strategy based on the light-on aggregation-induced emission (AIE) feature of tetraphenylethene (TPE) derivative to screen RNA-binding small molecules is presented. As a result of electrostatic interaction, the selected peptides can induce self-assembly of the TPE derivative to produce strong fluorescent emission; when the peptides are bound to RNA molecules, the TPE derivative is in the deaggregated form and shows no or minimum fluorescence. Based on the phenomenon, a competitive displacement assay combined with the TPE reporter was employed to characterize selected small molecules for their binding abilities to HIV-I RNAs. This AIE feature enables the fluorescence-off state of the TPE derivative in the presence of RNA-peptide complex to be "lightened up" quickly as the RNA-binding molecule is introduced and the peptide is competitively released. This strategy was carried out to test several small molecule binders, and the results are consistent with previous reports. This report gives an inspiring example of AIE-based fluorescent assay for HIV-I RNA-binding molecule screening, which may further be explored to build a drug screening platform for RNA-protein interference.Drug-induced hepatic damage has drawn great attention on public health problems. Drugs are biotransformed in the liver by enzymatic processes, accompanied by the production of reactive free radicals, which is the main cause of drug-induced hepatotoxicity. However, the limited penetration of optics makes the use of current luminescence imaging more difficult for acquiring free radicals mapping for lesion location, when applied to whole-body imaging in vivo. In this work, we develop an activatable nanoprobe based on Prussian blue (PB) that can combine magnetic resonance imaging (MRI) and photoacoustic imaging (PAI) for deep-tissue ONOO- imaging. We discover that ONOO- can oxidize FeII within PB into FeIII and meanwhile destroy the crystal structure of PB so that the strong absorption of PB at 710 nm that originated from the electron transferring between FeII and FeIII is greatly diminished. As a result, the reduced photoacoustic imaging (PA) signal of PB is able to function as an indicator for sensing ONOO-. Importantly, after reaction with ONOO-, the reduced size of PB results in the decrease of rotational correlation time (τR), leading to the activatable MRI signal for sensing ONOO-.0 التعليقات 0 المشاركات 25 مشاهدة 0 معاينة -
Over the last 30 years, genetically engineered DNA has been tested as novel vaccination strategy against various diseases, including human immunodeficiency virus (HIV), hepatitis B, several parasites, and cancers. However, the clinical breakthrough of the technique is confined by the low transfection efficacy and immunogenicity of the employed vaccines. Therefore, carrier materials were designed to prevent the rapid degradation and systemic clearance of DNA in the body. In this context, biopolymers are a particularly promising DNA vaccine carrier platform due to their beneficial biochemical and physical characteristics, including biocompatibility, stability, and low toxicity. This article reviews the applications, fabrication, and modification of biopolymers as carrier medium for genetic vaccines.
Although recent advances in immunotherapy have transformed the treatment landscape for many anatomically defined cancers, these therapies are currently not approved for patients diagnosed with cancer of unknown primary (CUP). Molecular cancer classification using gene expression profiling (GEP) assays has the potential to identify tumor type and putative primary cancers and thereby may allow consideration of immune checkpoint inhibitor (ICI) therapy options for a subset of patients with CUP. Herein, we evaluated and characterized the ability of a 92-gene assay (CancerTYPE ID) to provide a molecular diagnosis and identify putative tumor types that are known to be sensitive to ICI therapies in patients with CUP or uncertain diagnosis.
A total of 24,426 cases from a large-scale research database of 92-gene assay clinical cases were classified, of which 9,350 (38%) were predicted to have an ICI-eligible tumor type. All ICIs with approved indications as of March 2020 were included in the analysis. Non-small cell lung cancer (NSCLC) was the most frequent molecular diagnosis and accounted for 33% of the ICI-eligible tumor types identified and 13% of the overall reportable results. In addition to NSCLC, the assay also frequently identified urothelial carcinomas, gastric cancer, and head and neck squamous cell carcinoma. The distributions of identified tumor types with indications for ICI therapy were similar across age and gender.
Results suggest that molecular profiling with the 92-gene assay identifies a subset of ICI-eligible putative primary cancers in patients with CUP. We propose a treatment strategy based on available tests, including clinicopathologic features, GEP, and ICI biomarkers of response.
Results suggest that molecular profiling with the 92-gene assay identifies a subset of ICI-eligible putative primary cancers in patients with CUP. We propose a treatment strategy based on available tests, including clinicopathologic features, GEP, and ICI biomarkers of response.Due to the rapid development of industrial society, air pollution is becoming a serious problem which has being a huge threat to human health. Ultrafine particles (UFPs), one of the major air pollutants, are often the culprits of human diseases. At present, most of the toxicological studies of UFPs focus on their biological effects on lung cells and tissues, but there are less researches taking aim at the negative effects on functional proteins within the body. Therefore, we experimentally explored the effects of ultrafine carbon black (UFCB) on the structure and function of trypsin. After a short-term exposure to UFCB, the trypsin aromatic amino acid microenvironment, protein backbone and secondary structure were changed significantly, and the enzyme activity showed a trend that rose at first, then dropped. In addition, UFCB interacts with trypsin in the form of a complex. https://www.selleckchem.com/products/FTY720.html These studies demonstrated the negative effects of UFCB on trypsin, evidencing potential effects on animals and humans.The current study investigates the total bacterial contamination in various packed and unpacked ras malai samples of 14 different localities of Lahore, Pakistan. The bacterial colonies such as Bacillus sp. and Gamella sp. were isolated from ras malai samples and grown on agar-broth media under sterile environmental conditions. Serial dilution technique was used to compose the replicates to get a viable count of bacteria in the samples. Results indicated that in case of packed ras malai samples, maximum bacterial count was observed in Sample 1 (422 × 10-2 to 402 × 10-6 ) and minimum bacterial count was in Sample 4 (21 × 10-2 to 9.3 × 10-6 ). For unpacked ras malai samples, maximum bacterial count was in Sample 3 (200.3 × 10-2 to 181.3 × 10-6 ) and minimum bacterial count was observed in Sample 1 (110 × 10-2 to 90.4 × 10-6 ). It was concluded that the marketed samples contain more bacterial count as compared to the standard sterilization values. Such products could possibly become the cause of many health problems in children.
Proton pump inhibitors (eg, omeprazole) commonly are administered concurrently with nonsteroidal anti-inflammatory drugs (NSAIDs; eg, carprofen) as prophylaxis to decrease the risk of gastrointestinal (GI) injury. However, evidence to support this practice is weak, and it might exacerbate dysbiosis and inflammation.
To evaluate the effect of carprofen alone or combined with omeprazole in dogs. We hypothesized that coadministration of omeprazole and carprofen would significantly increase GI permeability and dysbiosis index (DI) compared to no treatment or carprofen alone.
Six healthy adult colony beagle dogs.
Gastrointestinal permeability and inflammation were assessed by serum lipopolysaccharide (LPS) concentration, plasma iohexol concentration, fecal DI, and fecal calprotectin concentration in a prospective, 3-period design. In the first 7-day period, dogs received no intervention (baseline). During the 2nd period, dogs received 4 mg/kg of carprofen q24h PO for 7 days. In the 3rd period, dogs receivetors for GI bleeding.
Inflammation plays an important role in the initiation and progression of cervicocranial arterial dissection (CCAD). New inflammatory indices derived from full cell blood count may be associated with increased risk of acute ischemic stroke (AIS) caused by CCAD. The goal of this study is to evaluate the diagnostic performances of neutrophil to lymphocyte ratio (NLR) and lymphocyte to monocyte ratio (LMR) in CCAD.
We retrospectively analyzed 52 patients with AIS caused by CCAD from emergency room (group I), 51 patients with CCAD from emergency room or clinic(group II) and 52 controls (group III), age and sex matched. Data were collected on the admission including NLR and LMR.
Neutrophil to lymphocyte ratio and LMR have significant differences among three groups, especially in group I vs both groups II and III (P < .001). There was a negative correlation between admission NLR and LMR. Low LMR level and high NLR level may be associated with severity of AIS caused by CCAD and significantly predict AIS in CCAD.
Over the last 30 years, genetically engineered DNA has been tested as novel vaccination strategy against various diseases, including human immunodeficiency virus (HIV), hepatitis B, several parasites, and cancers. However, the clinical breakthrough of the technique is confined by the low transfection efficacy and immunogenicity of the employed vaccines. Therefore, carrier materials were designed to prevent the rapid degradation and systemic clearance of DNA in the body. In this context, biopolymers are a particularly promising DNA vaccine carrier platform due to their beneficial biochemical and physical characteristics, including biocompatibility, stability, and low toxicity. This article reviews the applications, fabrication, and modification of biopolymers as carrier medium for genetic vaccines. Although recent advances in immunotherapy have transformed the treatment landscape for many anatomically defined cancers, these therapies are currently not approved for patients diagnosed with cancer of unknown primary (CUP). Molecular cancer classification using gene expression profiling (GEP) assays has the potential to identify tumor type and putative primary cancers and thereby may allow consideration of immune checkpoint inhibitor (ICI) therapy options for a subset of patients with CUP. Herein, we evaluated and characterized the ability of a 92-gene assay (CancerTYPE ID) to provide a molecular diagnosis and identify putative tumor types that are known to be sensitive to ICI therapies in patients with CUP or uncertain diagnosis. A total of 24,426 cases from a large-scale research database of 92-gene assay clinical cases were classified, of which 9,350 (38%) were predicted to have an ICI-eligible tumor type. All ICIs with approved indications as of March 2020 were included in the analysis. Non-small cell lung cancer (NSCLC) was the most frequent molecular diagnosis and accounted for 33% of the ICI-eligible tumor types identified and 13% of the overall reportable results. In addition to NSCLC, the assay also frequently identified urothelial carcinomas, gastric cancer, and head and neck squamous cell carcinoma. The distributions of identified tumor types with indications for ICI therapy were similar across age and gender. Results suggest that molecular profiling with the 92-gene assay identifies a subset of ICI-eligible putative primary cancers in patients with CUP. We propose a treatment strategy based on available tests, including clinicopathologic features, GEP, and ICI biomarkers of response. Results suggest that molecular profiling with the 92-gene assay identifies a subset of ICI-eligible putative primary cancers in patients with CUP. We propose a treatment strategy based on available tests, including clinicopathologic features, GEP, and ICI biomarkers of response.Due to the rapid development of industrial society, air pollution is becoming a serious problem which has being a huge threat to human health. Ultrafine particles (UFPs), one of the major air pollutants, are often the culprits of human diseases. At present, most of the toxicological studies of UFPs focus on their biological effects on lung cells and tissues, but there are less researches taking aim at the negative effects on functional proteins within the body. Therefore, we experimentally explored the effects of ultrafine carbon black (UFCB) on the structure and function of trypsin. After a short-term exposure to UFCB, the trypsin aromatic amino acid microenvironment, protein backbone and secondary structure were changed significantly, and the enzyme activity showed a trend that rose at first, then dropped. In addition, UFCB interacts with trypsin in the form of a complex. https://www.selleckchem.com/products/FTY720.html These studies demonstrated the negative effects of UFCB on trypsin, evidencing potential effects on animals and humans.The current study investigates the total bacterial contamination in various packed and unpacked ras malai samples of 14 different localities of Lahore, Pakistan. The bacterial colonies such as Bacillus sp. and Gamella sp. were isolated from ras malai samples and grown on agar-broth media under sterile environmental conditions. Serial dilution technique was used to compose the replicates to get a viable count of bacteria in the samples. Results indicated that in case of packed ras malai samples, maximum bacterial count was observed in Sample 1 (422 × 10-2 to 402 × 10-6 ) and minimum bacterial count was in Sample 4 (21 × 10-2 to 9.3 × 10-6 ). For unpacked ras malai samples, maximum bacterial count was in Sample 3 (200.3 × 10-2 to 181.3 × 10-6 ) and minimum bacterial count was observed in Sample 1 (110 × 10-2 to 90.4 × 10-6 ). It was concluded that the marketed samples contain more bacterial count as compared to the standard sterilization values. Such products could possibly become the cause of many health problems in children. Proton pump inhibitors (eg, omeprazole) commonly are administered concurrently with nonsteroidal anti-inflammatory drugs (NSAIDs; eg, carprofen) as prophylaxis to decrease the risk of gastrointestinal (GI) injury. However, evidence to support this practice is weak, and it might exacerbate dysbiosis and inflammation. To evaluate the effect of carprofen alone or combined with omeprazole in dogs. We hypothesized that coadministration of omeprazole and carprofen would significantly increase GI permeability and dysbiosis index (DI) compared to no treatment or carprofen alone. Six healthy adult colony beagle dogs. Gastrointestinal permeability and inflammation were assessed by serum lipopolysaccharide (LPS) concentration, plasma iohexol concentration, fecal DI, and fecal calprotectin concentration in a prospective, 3-period design. In the first 7-day period, dogs received no intervention (baseline). During the 2nd period, dogs received 4 mg/kg of carprofen q24h PO for 7 days. In the 3rd period, dogs receivetors for GI bleeding. Inflammation plays an important role in the initiation and progression of cervicocranial arterial dissection (CCAD). New inflammatory indices derived from full cell blood count may be associated with increased risk of acute ischemic stroke (AIS) caused by CCAD. The goal of this study is to evaluate the diagnostic performances of neutrophil to lymphocyte ratio (NLR) and lymphocyte to monocyte ratio (LMR) in CCAD. We retrospectively analyzed 52 patients with AIS caused by CCAD from emergency room (group I), 51 patients with CCAD from emergency room or clinic(group II) and 52 controls (group III), age and sex matched. Data were collected on the admission including NLR and LMR. Neutrophil to lymphocyte ratio and LMR have significant differences among three groups, especially in group I vs both groups II and III (P < .001). There was a negative correlation between admission NLR and LMR. Low LMR level and high NLR level may be associated with severity of AIS caused by CCAD and significantly predict AIS in CCAD.0 التعليقات 0 المشاركات 25 مشاهدة 0 معاينة -
In addition, IL-1β and NF-κB levels were found to be downregulated after 10% HS treatment. Therefore, results from the present study suggested that HS may protect against brain edema induced by TBI by modulating the expression levels of AQP4, NF-κB and IL-1β.Multi infarct dementia (MID) is a form of dementia that is preventable and treatable. However, at present, the drugs used in MID treatment were developed for Alzheimer's disease. While only a limited range of drugs is available, the incidence of MID is increasing year on year. The present study aimed to investigate the effect and underlying mechanisms of a combination of ginsenosides and astragalosides (CGA) on cognitive decline in rats with MID. A rat model of MID was established using micro-thromboembolism, and the behavioral changes in the rats were evaluated using the Morris water maze and open field tests at 60 days post-CGA intervention. The pathological morphology of the hippocampal CA1 area was observed using hematoxylin and eosin staining. https://www.selleckchem.com/products/oul232.html The contents of ATP, ADP and AMP were determined using high-performance liquid chromatography. Mitochondrial swelling and changes in the membrane potential in the hippocampus were detected using flow cytometry, and the changes in insulin, glutamate and γ-aminobutyric acid (GABA) content were detected using ELISA. Additionally, the expression of PI3K and AKT proteins was detected using western blot analysis. In a rat model of MID, CGA shortened the escape latency, increased the frequency of platform crossing, improved the disordered vertebral cell arrangement and reduced the cell number in the hippocampal CA1 area. CGA also reduced the degree of mitochondrial swelling, increased the mitochondrial membrane potential, and elevated the energy load and ATP content in the brain of rats with MID. Furthermore, CGA increased the insulin content and upregulated the expression of PI3K and AKT in the brain of rats with MID. In addition, in the rat model of MID, CGA also enhanced the movement time and the frequency of standing, and decreased the concentration of glutamate and GABA in the brain tissue. Amelioration of the cognitive decline in rats with MID by CGA was associated with its regulatory effect on the PI3K/AKT signaling pathway and neurotransmitter systems.It has been previously reported that the long non-coding RNA nuclear enriched abundant transcript 1 (NEAT1) can regulate cell apoptosis. The present study aimed to investigate the involvement of NEAT1 in premature ovarian failure (POF). A total of 60 patients with POF admitted at the Sixth Affiliated Hospital of Sun Yat-sen University between December 2016 and December 2018 were enrolled in the present study. Reverse transcription-quantitative PCR (RT-qPCR) was performed to measure NEAT1 expression level in tissue samples from patients with POF and healthy controls. Transient transfections were performed on two normal Chinese hamster ovary cell lines Lec8 and CHO, followed by RT-qPCR and western blot to evaluate gene interaction. Flow cytometry was performed to assess cell apoptosis. The results from the present study demonstrated that NEAT1 expression in ovarian tissues was significantly downregulated in patients with POF compared with healthy controls. Furthermore, the expression of p53 was upregulated in ovarian tissues from patients with POF compared with healthy controls and was inversely associated with NEAT1 expression. In hamster ovary cells, overexpression of NEAT1 led to inhibition of p53, whereas NEAT1 knockdown promoted the expression of p53. In addition, ovary cell apoptosis was inhibited following NEAT1 overexpression and stimulated following p53 overexpression. In conclusion, overexpression of NEAT1 may inhibit the expression of p53 and improve premature ovarian failure.MicroRNAs (miRNAs/miRs) negatively regulate gene expression and participate in various cellular processes. miRNA dysregulation is associated with cancer progression. The present study aimed to identify the miRNAs that participate in breast cancer tumorigenesis and determine the mechanism that underlies this. miRNA microarray data analysis and validation assays indicated that miR-376c-3p was downregulated in breast tumour tissues and breast cancer stem cells (BCSCs) compared with adjacent non-cancerous tissues and MCF-10A cells, respectively. Ras-related protein Rab-2A (RAB2A) was predicted as a target of miR-376c-3p, which was confirmed by conducting further experiments. miR-376c-3p regulated the BCSC population and the expression of stem cell regulatory genes by targeting RAB2A. By performing mammosphere, Cell Counting Kit-8, colony formation and transwell invasion assays, it was demonstrated that miR-376c-3p also inhibited BCSC self-renewal, proliferation and invasion by regulating RAB2A expression. Using a xenograft mouse model, it was revealed that miR-376c-3p overexpression suppressed breast cancer growth in vivo. In conclusion, the results indicated that miR-376c-3p targeted RAB2A to regulate BCSC fate and properties; therefore, miR-376c-3p may serve as a potential therapeutic target for breast cancer.Peptide profiles change significantly with aging and peptide biomarkers discovered in adult patients may not be suitable for the evaluation of pediatric patients. The present study was designed to explore alterations in the serum peptidome profile of pediatric patients with IgA nephropathy (IgAN). A total of 17 children diagnosed with IgAN were recruited as the experimental group, 11 sex-matched healthy children were recruited as a healthy control group and 18 sex-matched children with other glomerular diseases were recruited as a disease control group. Serum peptides of each subject were enriched and analyzed by liquid chromatography with tandem mass spectrometry and the subsequently identified IgAN-specific peptides were evaluated using Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analysis. Subsequently, the function of the IgAN-specific peptides was predicted via sequence comparison with other known functional bioactive peptides. A total of 123 peptides with a fold change >2 (P5 (P less then 0.
In addition, IL-1β and NF-κB levels were found to be downregulated after 10% HS treatment. Therefore, results from the present study suggested that HS may protect against brain edema induced by TBI by modulating the expression levels of AQP4, NF-κB and IL-1β.Multi infarct dementia (MID) is a form of dementia that is preventable and treatable. However, at present, the drugs used in MID treatment were developed for Alzheimer's disease. While only a limited range of drugs is available, the incidence of MID is increasing year on year. The present study aimed to investigate the effect and underlying mechanisms of a combination of ginsenosides and astragalosides (CGA) on cognitive decline in rats with MID. A rat model of MID was established using micro-thromboembolism, and the behavioral changes in the rats were evaluated using the Morris water maze and open field tests at 60 days post-CGA intervention. The pathological morphology of the hippocampal CA1 area was observed using hematoxylin and eosin staining. https://www.selleckchem.com/products/oul232.html The contents of ATP, ADP and AMP were determined using high-performance liquid chromatography. Mitochondrial swelling and changes in the membrane potential in the hippocampus were detected using flow cytometry, and the changes in insulin, glutamate and γ-aminobutyric acid (GABA) content were detected using ELISA. Additionally, the expression of PI3K and AKT proteins was detected using western blot analysis. In a rat model of MID, CGA shortened the escape latency, increased the frequency of platform crossing, improved the disordered vertebral cell arrangement and reduced the cell number in the hippocampal CA1 area. CGA also reduced the degree of mitochondrial swelling, increased the mitochondrial membrane potential, and elevated the energy load and ATP content in the brain of rats with MID. Furthermore, CGA increased the insulin content and upregulated the expression of PI3K and AKT in the brain of rats with MID. In addition, in the rat model of MID, CGA also enhanced the movement time and the frequency of standing, and decreased the concentration of glutamate and GABA in the brain tissue. Amelioration of the cognitive decline in rats with MID by CGA was associated with its regulatory effect on the PI3K/AKT signaling pathway and neurotransmitter systems.It has been previously reported that the long non-coding RNA nuclear enriched abundant transcript 1 (NEAT1) can regulate cell apoptosis. The present study aimed to investigate the involvement of NEAT1 in premature ovarian failure (POF). A total of 60 patients with POF admitted at the Sixth Affiliated Hospital of Sun Yat-sen University between December 2016 and December 2018 were enrolled in the present study. Reverse transcription-quantitative PCR (RT-qPCR) was performed to measure NEAT1 expression level in tissue samples from patients with POF and healthy controls. Transient transfections were performed on two normal Chinese hamster ovary cell lines Lec8 and CHO, followed by RT-qPCR and western blot to evaluate gene interaction. Flow cytometry was performed to assess cell apoptosis. The results from the present study demonstrated that NEAT1 expression in ovarian tissues was significantly downregulated in patients with POF compared with healthy controls. Furthermore, the expression of p53 was upregulated in ovarian tissues from patients with POF compared with healthy controls and was inversely associated with NEAT1 expression. In hamster ovary cells, overexpression of NEAT1 led to inhibition of p53, whereas NEAT1 knockdown promoted the expression of p53. In addition, ovary cell apoptosis was inhibited following NEAT1 overexpression and stimulated following p53 overexpression. In conclusion, overexpression of NEAT1 may inhibit the expression of p53 and improve premature ovarian failure.MicroRNAs (miRNAs/miRs) negatively regulate gene expression and participate in various cellular processes. miRNA dysregulation is associated with cancer progression. The present study aimed to identify the miRNAs that participate in breast cancer tumorigenesis and determine the mechanism that underlies this. miRNA microarray data analysis and validation assays indicated that miR-376c-3p was downregulated in breast tumour tissues and breast cancer stem cells (BCSCs) compared with adjacent non-cancerous tissues and MCF-10A cells, respectively. Ras-related protein Rab-2A (RAB2A) was predicted as a target of miR-376c-3p, which was confirmed by conducting further experiments. miR-376c-3p regulated the BCSC population and the expression of stem cell regulatory genes by targeting RAB2A. By performing mammosphere, Cell Counting Kit-8, colony formation and transwell invasion assays, it was demonstrated that miR-376c-3p also inhibited BCSC self-renewal, proliferation and invasion by regulating RAB2A expression. Using a xenograft mouse model, it was revealed that miR-376c-3p overexpression suppressed breast cancer growth in vivo. In conclusion, the results indicated that miR-376c-3p targeted RAB2A to regulate BCSC fate and properties; therefore, miR-376c-3p may serve as a potential therapeutic target for breast cancer.Peptide profiles change significantly with aging and peptide biomarkers discovered in adult patients may not be suitable for the evaluation of pediatric patients. The present study was designed to explore alterations in the serum peptidome profile of pediatric patients with IgA nephropathy (IgAN). A total of 17 children diagnosed with IgAN were recruited as the experimental group, 11 sex-matched healthy children were recruited as a healthy control group and 18 sex-matched children with other glomerular diseases were recruited as a disease control group. Serum peptides of each subject were enriched and analyzed by liquid chromatography with tandem mass spectrometry and the subsequently identified IgAN-specific peptides were evaluated using Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analysis. Subsequently, the function of the IgAN-specific peptides was predicted via sequence comparison with other known functional bioactive peptides. A total of 123 peptides with a fold change >2 (P5 (P less then 0.0 التعليقات 0 المشاركات 25 مشاهدة 0 معاينة -
Wilson's disease (WD) is a rare autosomal-recessive inborn error of copper metabolism characterized by the toxic accumulation of copper in liver, brain, cornea, and other tissues. It has a variable clinical presentation. Musculoskeletal presentations are very unusual. We report a 17-year-old male who presented to us with juvenile idiopathic arthritis (JIA), which later proved to be a case of WD.Objectives Achilles tendon rupture (ATR) in adults often results from sporting activities, especially in young adults. There is no consensus in the literature on the best treatment approach in the treatment of these ruptures. The objective of this study was to evaluate the clinical long-term results of the augmented ATR repair using the modified Lindholm procedure (MLP). Methods Patients who underwent MLP due to ATR in the orthopedics and traumatology clinic of our hospital between 2007 and 2014 were retrospectively evaluated. Medical history of the patients was noted, and preoperative physical examination was routinely performed using the Thompson compression test. Patients' demographic data such as age and gender, tendon rupture side, postoperative follow-up duration, and gap range values were recorded and evaluated. Results The mean age of the patients was 29.43 ± 7.10 years. The mean postoperative follow-up duration was 50.1 ± 8.20 months. Of the patients, 16 were injured during football, 10 during basketball, 2 during volleyball, and the remaining 8 during other sporting activities. When Arner-Lindholm scores were evaluated during follow-up, excellent outcome was achieved in 30 patients and good outcome was achieved in 6 patients, whereas there was no patient with poor outcome. None of the patients developed tendon re-rupture. At the end of the fourth postoperative month, the range of ankle motion was 100% in all patients. Conclusions In patients with spontaneous AT tendon rupture, MLP seems to prevent the re-rupture in the long-term period and should be considered as a safe procedure to repair ATR.Chondrosarcoma is a unique kind of tumor that originates from the cartilage-producing neoplastic mesenchymal cells and appears in both the appendicular and atlantoaxial skeleton. It is the second most prevalent neoplastic bone tumor, with an occurrence of 0.79/100,000/year. The biological presentation of this cancer fluctuates extensively, depending on the grade and anatomical location. Since chondrosarcoma is predominantly resistant to conventional chemo- and radiation therapy, surgical resection remains the sole curative treatment, although at present new treatment modalities are under investigation.Introduction Increasing demands for healthcare manpower has necessitated the utilization of advanced practice providers (APPs). The effect of APPs in primary care has been well-characterized but is less studied in surgical subspecialties. The objective of this study is to assess the patient acceptability of APPs in an outpatient neurosurgery setting. Methods We conducted a prospective, survey-based study among 78 adult patients in the neurosurgical outpatient clinic. The survey consisted of 10 questions assessing the hypothetical acceptability of care provided by neurosurgeons and APPs. These were compared as pre-specified dyads, with patients blinded to dyad composition. The data were analyzed with Chi-square tests. Results Patients preferred to see their neurosurgeon for their first clinic visit even with a longer lag time (29% acceptability difference, p = 0.012). Patients also preferred to see the neurosurgeon for their first postoperative visit (20% difference, p = 0.009). For all visits, patients preferred to see an APP if the clinic visit would be on time, rather than see the surgeon with a significant delay (30% difference, p = 0.0002). https://www.selleckchem.com/products/oul232.html If their visit was scheduled with an APP, patients preferred that the neurosurgeon review their treatment plan before they left the clinic (15% difference, p = 0.04). Overall, seeing an APP was acceptable if patients were informed ahead of time (37% difference, p less then 0.0001). Conclusions Team-based care utilizing APPs is acceptable to patients. Patients had strong preferences for seeing their surgeon for the first neurosurgical clinic visit and first post-operative visit. Patients were satisfied with seeing an APP if they could be seen more expeditiously. Patients also preferred to know ahead of time if they were going to see an APP.Shoulder injury related to vaccine administration (SIRVA) is an increasingly reported phenomenon that causes inflammation of surrounding structures, along with pain and decreased range of motion of the affected shoulder. Current literature emphasizes proper injection techniques and locations to decrease incidence; however, there is limited information available on successful treatments. The aim of this report is to describe a case of SIRVA and review treatment options, specifically the role of osteopathic manipulative medicine (OMM) in the resolution of symptoms refractory to standard care. Here we present a case of chronic SIRVA in a 58-year-old female due to a poorly administered influenza vaccination with emphasis on a stepwise osteopathic therapy approach as a lasting treatment to decrease the effects of the inflammatory process and improve daily function of the shoulder. OMM, with the option of anesthesia, can be performed in outpatient family medicine practices as a noninvasive and safe adjunct treatment. Specifically, the Spencer technique has been shown to improve shoulder-related pathologies that include adhesions, capsulitis, and inflammation and was used in this case under anesthesia. The patient reported good improvement in her symptoms and increased range of motion. SIRVA is an underdiagnosed phenomenon that involves inflammation of surrounding structures after a vaccine administration. In chronic cases, such as in this patient, OMM may be enhanced with the use of anesthesia to optimize the treatment's effect on scar tissue and fibrosis.Introduction Systemic sclerosis (SSc) is known to increase the risk of ischemic stroke and other cerebrovascular events. It is, however, unclear if SSc negatively impacts the outcomes of ischemic stroke hospitalizations. This study aims to compare the outcomes of patients primarily admitted for ischemic stroke with and without a secondary diagnosis of SSc. Methods Data were extracted from the National Inpatient Sample (NIS) 2016 and 2017 database. NIS is the largest hospitalization database in the United States. We searched the database for hospitalizations of adult patients admitted with a principal diagnosis of ischemic stroke, with and without SSc as the secondary diagnosis using International Classification of Diseases, Tenth Revision (ICD-10) codes. The primary outcome was inpatient mortality, and secondary outcomes were hospital length of stay (LOS), total hospital charge, odds of undergoing mechanical thrombectomy, and receiving tissue plasminogen activator (TPA). Multivariate logistic and linear regression analysis was used to adjust for confounders.
Wilson's disease (WD) is a rare autosomal-recessive inborn error of copper metabolism characterized by the toxic accumulation of copper in liver, brain, cornea, and other tissues. It has a variable clinical presentation. Musculoskeletal presentations are very unusual. We report a 17-year-old male who presented to us with juvenile idiopathic arthritis (JIA), which later proved to be a case of WD.Objectives Achilles tendon rupture (ATR) in adults often results from sporting activities, especially in young adults. There is no consensus in the literature on the best treatment approach in the treatment of these ruptures. The objective of this study was to evaluate the clinical long-term results of the augmented ATR repair using the modified Lindholm procedure (MLP). Methods Patients who underwent MLP due to ATR in the orthopedics and traumatology clinic of our hospital between 2007 and 2014 were retrospectively evaluated. Medical history of the patients was noted, and preoperative physical examination was routinely performed using the Thompson compression test. Patients' demographic data such as age and gender, tendon rupture side, postoperative follow-up duration, and gap range values were recorded and evaluated. Results The mean age of the patients was 29.43 ± 7.10 years. The mean postoperative follow-up duration was 50.1 ± 8.20 months. Of the patients, 16 were injured during football, 10 during basketball, 2 during volleyball, and the remaining 8 during other sporting activities. When Arner-Lindholm scores were evaluated during follow-up, excellent outcome was achieved in 30 patients and good outcome was achieved in 6 patients, whereas there was no patient with poor outcome. None of the patients developed tendon re-rupture. At the end of the fourth postoperative month, the range of ankle motion was 100% in all patients. Conclusions In patients with spontaneous AT tendon rupture, MLP seems to prevent the re-rupture in the long-term period and should be considered as a safe procedure to repair ATR.Chondrosarcoma is a unique kind of tumor that originates from the cartilage-producing neoplastic mesenchymal cells and appears in both the appendicular and atlantoaxial skeleton. It is the second most prevalent neoplastic bone tumor, with an occurrence of 0.79/100,000/year. The biological presentation of this cancer fluctuates extensively, depending on the grade and anatomical location. Since chondrosarcoma is predominantly resistant to conventional chemo- and radiation therapy, surgical resection remains the sole curative treatment, although at present new treatment modalities are under investigation.Introduction Increasing demands for healthcare manpower has necessitated the utilization of advanced practice providers (APPs). The effect of APPs in primary care has been well-characterized but is less studied in surgical subspecialties. The objective of this study is to assess the patient acceptability of APPs in an outpatient neurosurgery setting. Methods We conducted a prospective, survey-based study among 78 adult patients in the neurosurgical outpatient clinic. The survey consisted of 10 questions assessing the hypothetical acceptability of care provided by neurosurgeons and APPs. These were compared as pre-specified dyads, with patients blinded to dyad composition. The data were analyzed with Chi-square tests. Results Patients preferred to see their neurosurgeon for their first clinic visit even with a longer lag time (29% acceptability difference, p = 0.012). Patients also preferred to see the neurosurgeon for their first postoperative visit (20% difference, p = 0.009). For all visits, patients preferred to see an APP if the clinic visit would be on time, rather than see the surgeon with a significant delay (30% difference, p = 0.0002). https://www.selleckchem.com/products/oul232.html If their visit was scheduled with an APP, patients preferred that the neurosurgeon review their treatment plan before they left the clinic (15% difference, p = 0.04). Overall, seeing an APP was acceptable if patients were informed ahead of time (37% difference, p less then 0.0001). Conclusions Team-based care utilizing APPs is acceptable to patients. Patients had strong preferences for seeing their surgeon for the first neurosurgical clinic visit and first post-operative visit. Patients were satisfied with seeing an APP if they could be seen more expeditiously. Patients also preferred to know ahead of time if they were going to see an APP.Shoulder injury related to vaccine administration (SIRVA) is an increasingly reported phenomenon that causes inflammation of surrounding structures, along with pain and decreased range of motion of the affected shoulder. Current literature emphasizes proper injection techniques and locations to decrease incidence; however, there is limited information available on successful treatments. The aim of this report is to describe a case of SIRVA and review treatment options, specifically the role of osteopathic manipulative medicine (OMM) in the resolution of symptoms refractory to standard care. Here we present a case of chronic SIRVA in a 58-year-old female due to a poorly administered influenza vaccination with emphasis on a stepwise osteopathic therapy approach as a lasting treatment to decrease the effects of the inflammatory process and improve daily function of the shoulder. OMM, with the option of anesthesia, can be performed in outpatient family medicine practices as a noninvasive and safe adjunct treatment. Specifically, the Spencer technique has been shown to improve shoulder-related pathologies that include adhesions, capsulitis, and inflammation and was used in this case under anesthesia. The patient reported good improvement in her symptoms and increased range of motion. SIRVA is an underdiagnosed phenomenon that involves inflammation of surrounding structures after a vaccine administration. In chronic cases, such as in this patient, OMM may be enhanced with the use of anesthesia to optimize the treatment's effect on scar tissue and fibrosis.Introduction Systemic sclerosis (SSc) is known to increase the risk of ischemic stroke and other cerebrovascular events. It is, however, unclear if SSc negatively impacts the outcomes of ischemic stroke hospitalizations. This study aims to compare the outcomes of patients primarily admitted for ischemic stroke with and without a secondary diagnosis of SSc. Methods Data were extracted from the National Inpatient Sample (NIS) 2016 and 2017 database. NIS is the largest hospitalization database in the United States. We searched the database for hospitalizations of adult patients admitted with a principal diagnosis of ischemic stroke, with and without SSc as the secondary diagnosis using International Classification of Diseases, Tenth Revision (ICD-10) codes. The primary outcome was inpatient mortality, and secondary outcomes were hospital length of stay (LOS), total hospital charge, odds of undergoing mechanical thrombectomy, and receiving tissue plasminogen activator (TPA). Multivariate logistic and linear regression analysis was used to adjust for confounders.0 التعليقات 0 المشاركات 24 مشاهدة 0 معاينة -
We conducted an extended time course study to compare markers of liver damage, inflammation and proliferation between male and female **** exposed postnatally to 600 nmol ABP or 10 mg/kg DEN, and also in HBV transgenic (HBVTg) ****, over the duration of time that **** are normally maintained for standard liver tumor development protocols. Postnatal exposure to either ABP or DEN produced no evidence of either acute or chronic hepatocyte damage, liver inflammation or proliferation in either male or female ****. In contrast, HBVTg **** showed increased liver damage, inflammation and proliferation with age, but with no observed sex difference. These findings suggest that although chronic liver damage, inflammation and proliferation may be drivers for liver cancer development, they are unlikely to contribute directly to observed sex differences in liver tumor risk.The specific mechanism of paraquat (PQ)-induced acute lung injury (ALI) is unclear, though inflammation is a likely contributor. Amlexanox, a TANK binding kinase 1 (TBK1) inhibitor, is a strong anti-inflammatory drug. We investigated the role of TBK1 and the potential therapeutic effect of amlexanox in the pathogenesis of PQ-induced ALI. After 30 mg/kg PQ treatment for 72 h, mouse lung pathological injury occurred, and the protein concentration in alveolar lavage fluid was increased. Next, RAW264.7 mouse macrophages were treated with 100 μM PQ for 24 h, which decreased cell viability. PQ induced oxidative damage and increased IL-1β, IFNβ, NF-κBp65, IRF3, and pTBK1/TBK1 levels in mouse lungs and RAW264.7 cells. Inhibiting the activation of TBK1 with amlexanox (100 mg/kg in **** and 50 μM in RAW264.7 cells) attenuated mouse lung injury and decreased the protein concentration in alveolar lavage fluid. Further, amlexanox relieved the oxidative damage in mouse lungs and RAW264.7 cells, reduced the levels of inflammatory factors such as IL-1β and IFNβ, and inhibited the activation of NF-κBp65 and IRF3. These results suggest that TBK1 plays a key role in the pathogenesis of PQ-induced ALI. Further, amlexanox treatment alleviates PQ-induced ALI by inhibiting the TBK1-NF-κB/IRF3 signalling pathway. Our study provides evidence that TBK1 inhibition by amlexanox alleviates PQ-induced ALI and may be a new therapeutic strategy.The kappa opioid receptor (KOP) system modulates social play responding, however a paucity of studies have examined effects on social motivation and cognition in the absence of play. Prenatal exposure to the anti-epileptic and mood stabiliser valproic acid (VPA) is associated with impaired social responding and altered gene expression of KOP (oprk1) and dynorphin (pdyn) in several brain regions. The present study examined if pharmacological modulation of KOP altered social motivation and cognition, immediate early gene (IEG) and oprk1-pdyn expression in adolescent male rats and rats prenatally exposed to VPA. In control rats, the KOP antagonist DIPPA enhanced sociability, while both DIPPA and the KOP agonist U50488 decreased social novelty preference. In rats exposed prenatally to VPA, neither U50488 nor DIPPA altered sociability or social novelty preference. Analysis of IEG expression revealed that DIPPA reduced expression of egr-1 expression in the prefrontal cortex of control rats and U50488 increased junb expression in the PFC of both control and VPA-exposed rats. VPA-exposed rats exhibited increased expression of oprk1 and pdyn in the prefrontal cortex and amygdala compared with control rats. DIPPA and U50488 increased oprk1 expression in the amygdala of control rats and decreased oprk1 expression in the prefrontal cortex of VPA-exposed rats. Taken together, these data demonstrate that pharmacological modulation of the KOP system alters social motivation and cognition in control rats, an effect not observed in rats prenatally exposed to VPA. These data provide support that prenatal exposure to VPA is associated with alterations in the expression and functionality of KOP system.Bisphenol A (BPA) has a variety of adverse effects on human health; therefore, BPA analogs are increasingly used as replacements. Notably, recent studies have revealed that BPA exposure induced hepatic lipid accumulation, but few studies are available regarding the similar effects of other bisphenol analogues (BPs). Thus, in the present study, a high-content screening (HCS) assay was performed to simultaneously evaluate the hepatic lipid accumulation of 13 BPs in vitro. The BPs induced lipid deposition in HepG2 cells ranking as below 4,4'-thiodiphenol (TDP) less then bisphenol S (BPS) less then 4,4'-dihydroxybenzophenone (DHBP) less then tetrabromobisphenol A (TBBPA) less then tetrachlorobisphenol A (TCBPA) less then bisphenol E (BPE) less then bisphenol F (BPF) less then bisphenol B (BPB) less then bisphenol AF (BPAF) less then bisphenol A (BPA) less then bisphenol C (BPC) less then tetramethylbisphenol A (TMBPA) less then bisphenol AP (BPAP). Meanwhile, Oil Red O staining and triacylglycerol detection further validated the lipid accumulation elicited by the latter 8 BPs, which exhibited the more significant effects on lipid deposition. Mechanistically, significantly increased expressions of genes involved in fatty acid synthesis and nuclear receptors and decreased levels of genes associated with fatty acid β-oxidation were observed under BPs treatment. Therefore, the present work is the first to systematically provide direct evidence for BPs-induced hepatic lipid accumulation in vitro via HCS, which can be helpful for safety assessments of BPs.Neurogenesis process in the chronic phase of ischemic stroke has become the focus of research on stroke treatment recently, mainly through the activation of related pathways to increase the differentiation of neural stem cells (NSCs) in the brain sub-ventricular zone (SVZ) and subgranular zone (SGZ) of hippocampal dentate gyrus (DG) areas into neurons, promoting neurogenesis. While there is still debate about the longevity of active adult neurogenesis in humans, the SVZ and SGZ have the capacity to upregulate neurogenesis in response to cerebral ischemia, which opens discussion about potential treatment strategies to harness this neuronal regenerative response. https://www.selleckchem.com/products/zx703.html Wnt signaling pathway is one of the most important approaches potentially targeting on neurogenesis after cerebral ischemia, appropriate activation of which in NSCs may help to improve the sequelae of cerebral ischemia. Various therapeutic approaches are explored on preclinical stage to target endogenous neurogenesis induced by Wnt signaling after stroke onset.
We conducted an extended time course study to compare markers of liver damage, inflammation and proliferation between male and female mice exposed postnatally to 600 nmol ABP or 10 mg/kg DEN, and also in HBV transgenic (HBVTg) mice, over the duration of time that mice are normally maintained for standard liver tumor development protocols. Postnatal exposure to either ABP or DEN produced no evidence of either acute or chronic hepatocyte damage, liver inflammation or proliferation in either male or female mice. In contrast, HBVTg mice showed increased liver damage, inflammation and proliferation with age, but with no observed sex difference. These findings suggest that although chronic liver damage, inflammation and proliferation may be drivers for liver cancer development, they are unlikely to contribute directly to observed sex differences in liver tumor risk.The specific mechanism of paraquat (PQ)-induced acute lung injury (ALI) is unclear, though inflammation is a likely contributor. Amlexanox, a TANK binding kinase 1 (TBK1) inhibitor, is a strong anti-inflammatory drug. We investigated the role of TBK1 and the potential therapeutic effect of amlexanox in the pathogenesis of PQ-induced ALI. After 30 mg/kg PQ treatment for 72 h, mouse lung pathological injury occurred, and the protein concentration in alveolar lavage fluid was increased. Next, RAW264.7 mouse macrophages were treated with 100 μM PQ for 24 h, which decreased cell viability. PQ induced oxidative damage and increased IL-1β, IFNβ, NF-κBp65, IRF3, and pTBK1/TBK1 levels in mouse lungs and RAW264.7 cells. Inhibiting the activation of TBK1 with amlexanox (100 mg/kg in mice and 50 μM in RAW264.7 cells) attenuated mouse lung injury and decreased the protein concentration in alveolar lavage fluid. Further, amlexanox relieved the oxidative damage in mouse lungs and RAW264.7 cells, reduced the levels of inflammatory factors such as IL-1β and IFNβ, and inhibited the activation of NF-κBp65 and IRF3. These results suggest that TBK1 plays a key role in the pathogenesis of PQ-induced ALI. Further, amlexanox treatment alleviates PQ-induced ALI by inhibiting the TBK1-NF-κB/IRF3 signalling pathway. Our study provides evidence that TBK1 inhibition by amlexanox alleviates PQ-induced ALI and may be a new therapeutic strategy.The kappa opioid receptor (KOP) system modulates social play responding, however a paucity of studies have examined effects on social motivation and cognition in the absence of play. Prenatal exposure to the anti-epileptic and mood stabiliser valproic acid (VPA) is associated with impaired social responding and altered gene expression of KOP (oprk1) and dynorphin (pdyn) in several brain regions. The present study examined if pharmacological modulation of KOP altered social motivation and cognition, immediate early gene (IEG) and oprk1-pdyn expression in adolescent male rats and rats prenatally exposed to VPA. In control rats, the KOP antagonist DIPPA enhanced sociability, while both DIPPA and the KOP agonist U50488 decreased social novelty preference. In rats exposed prenatally to VPA, neither U50488 nor DIPPA altered sociability or social novelty preference. Analysis of IEG expression revealed that DIPPA reduced expression of egr-1 expression in the prefrontal cortex of control rats and U50488 increased junb expression in the PFC of both control and VPA-exposed rats. VPA-exposed rats exhibited increased expression of oprk1 and pdyn in the prefrontal cortex and amygdala compared with control rats. DIPPA and U50488 increased oprk1 expression in the amygdala of control rats and decreased oprk1 expression in the prefrontal cortex of VPA-exposed rats. Taken together, these data demonstrate that pharmacological modulation of the KOP system alters social motivation and cognition in control rats, an effect not observed in rats prenatally exposed to VPA. These data provide support that prenatal exposure to VPA is associated with alterations in the expression and functionality of KOP system.Bisphenol A (BPA) has a variety of adverse effects on human health; therefore, BPA analogs are increasingly used as replacements. Notably, recent studies have revealed that BPA exposure induced hepatic lipid accumulation, but few studies are available regarding the similar effects of other bisphenol analogues (BPs). Thus, in the present study, a high-content screening (HCS) assay was performed to simultaneously evaluate the hepatic lipid accumulation of 13 BPs in vitro. The BPs induced lipid deposition in HepG2 cells ranking as below 4,4'-thiodiphenol (TDP) less then bisphenol S (BPS) less then 4,4'-dihydroxybenzophenone (DHBP) less then tetrabromobisphenol A (TBBPA) less then tetrachlorobisphenol A (TCBPA) less then bisphenol E (BPE) less then bisphenol F (BPF) less then bisphenol B (BPB) less then bisphenol AF (BPAF) less then bisphenol A (BPA) less then bisphenol C (BPC) less then tetramethylbisphenol A (TMBPA) less then bisphenol AP (BPAP). Meanwhile, Oil Red O staining and triacylglycerol detection further validated the lipid accumulation elicited by the latter 8 BPs, which exhibited the more significant effects on lipid deposition. Mechanistically, significantly increased expressions of genes involved in fatty acid synthesis and nuclear receptors and decreased levels of genes associated with fatty acid β-oxidation were observed under BPs treatment. Therefore, the present work is the first to systematically provide direct evidence for BPs-induced hepatic lipid accumulation in vitro via HCS, which can be helpful for safety assessments of BPs.Neurogenesis process in the chronic phase of ischemic stroke has become the focus of research on stroke treatment recently, mainly through the activation of related pathways to increase the differentiation of neural stem cells (NSCs) in the brain sub-ventricular zone (SVZ) and subgranular zone (SGZ) of hippocampal dentate gyrus (DG) areas into neurons, promoting neurogenesis. While there is still debate about the longevity of active adult neurogenesis in humans, the SVZ and SGZ have the capacity to upregulate neurogenesis in response to cerebral ischemia, which opens discussion about potential treatment strategies to harness this neuronal regenerative response. https://www.selleckchem.com/products/zx703.html Wnt signaling pathway is one of the most important approaches potentially targeting on neurogenesis after cerebral ischemia, appropriate activation of which in NSCs may help to improve the sequelae of cerebral ischemia. Various therapeutic approaches are explored on preclinical stage to target endogenous neurogenesis induced by Wnt signaling after stroke onset.0 التعليقات 0 المشاركات 26 مشاهدة 0 معاينة -
The risk of venous thromboembolism (VTE) is increased in patients with cancer and is greatest in those with cancers of the pancreas, stomach, brain, lung and ovary, late stage disease and in those undergoing treatment including chemotherapy, hormonal therapy, or surgery. VTE in patients with cancer is associated with a variety of adverse consequences including an increased risk of VTE recurrence, major bleeding, and early mortality. A VTE risk score for ambulatory patients receiving cancer chemotherapy has been extensively validated and has been used to select high risk patients for thromboprophylaxis trials. Several randomized controlled trials (RCTs) and meta-analyses of these trials have confirmed that LMWHs can significantly reduce the risk of VTE in patients with cancer. While the direct oral anticoagulants (DOACs) have been approved for the general population, previous guideline panels discouraged their use due to a lack of cancer-specific data. Recently RCTs for the treatment of established VTE in patients with cancer have demonstrated that the risk of recurrent VTE is lower while the risk of bleeding greater with DOACs compared to LMWH. Two thromboprophylaxis trials comparing low dose DOACs to placebo in high risk patients receiving cancer therapy have recently reported similar rates of VTE occurrence at 6 months in the control arms. A meta-analysis of the pooled results from these trials in higher risk ambulatory patients receiving cancer therapy confirmed a significant reduction in overall VTE incidence as well as pre-planned secondary outcomes on treatment. Several clinical practice guidelines addressing VTE in patients with malignant disease have been updated including those from the American Society of Clinical Oncology (ASCO). The addition of DOACs as an option for the management of VTE in patients with cancer is the latest major change to previous guidelines issued by these organizations. The updated recommendations from these guidelines are summarized in this review.Patients with multiple myeloma (MM) have an increased risk of venous thromboembolism (VTE) compared to the general population. This risk is highest during the first year of diagnosis and subsequently decreases over time. https://www.selleckchem.com/products/byl719.html Development of VTE in patients with MM is associated with inferior outcomes, with patients with VTE and MM having an increased risk of death compared to those with MM without VTE. Primary thromboprophylaxis has the potential to decrease risk of VTEksanfilippo@wustl.edu (K.M. Sanfilippo) in MM and improve outcomes. Current studies assessing thromboprophylaxis in MM excluded patients at high risk of VTE. A meta-analysis of trials of primary thromboprophylaxis in ambulatory cancer patients at high risk of VTE identified by use of a risk-prediction score found a reduction in risk of VTE with prophylaxis with no significant increase in risk of major bleeding. However, these trials contained relatively few patients with MM. Three clinical risk prediction scores are available to assess risk of VTE in MM 1) the International Myeloma Working Group (IMWG)/National Comprehensive Cancer Network (NCCN); 2) the SAVED score; and 3) the IMPEDE VTE score. The latter two have recently been shown to outperform the IMWG/ NCCN score for predicting VTE in MM. Biomarkers have the potential to improve prediction of VTE in patients with MM. Future research should focus on the addition of biomarkers to available risk scores in MM to improve discrimination in this high-risk patient population.A B S T R A C T Antithrombotic therapy (anticoagulation or antiplatelet therapy) is frequently prescribed in cancer patients for prior or new indications such as venous thromboembolism, secondary prevention of arterial thrombosis or atrial fibrillation. Therefore, it is not uncommon for thrombocytopenic cancer patients to have an indication for antithrombotic therapy. Thrombocytopenia does not reduce the risk of recurrent thrombosis. The bleeding risk with anticoagulation appears to increase when platelets are less then 50×109/L, but individual platelet counts are poor predictors of bleeding. Management options when platelets are less then 50×109/L include no change, temporarily withholding antithrombotic therapy, reducing dose, changing the regimen, and increasing the platelet transfusion threshold. There are currently no data on use of direct oral anticoagulants when platelets are below 50×109/L, and there is reason in restricting their use. Little is known on antiplatelet therapy in this setting, although recent data suggest the prognostic importance and apparent safety of aspirin in acute myocardial infarction and thrombocytopenia. This paper will review the evidence, guidelines, current practice and ongoing studies on anticoagulation and antiplatelet therapy in thrombocytopenic patients with cancer.Since the introduction of all-trans retinoic acid and, more recently, arsenic trioxide into the therapy of acute promyelocytic leukemia (APL), significant improvements in patient outcomes have been achieved, and this disease has become the most curable subtype of acute myeloid leukemia. However, while primary leukemia resistance has virtually disappeared, a sizable fraction of APL patients still die before or during induction therapy. Hemorrhagic death still remains the major problem during this early phase of treatment and, to a lesser extent, deaths due to infection, differentiation syndrome and other causes. Patients with APL typically present with a range of laboratory abnormalities consistent with the diagnosis of disseminated intravascular coagulation and hyperfibrinolysis. This APL-associated coagulopathy, as a result of a dysregulation of the hemostatic system due to the imbalance between procoagulant, anticoagulant and profibrinolytic mechanisms, may show a variety of clinical manifestations, ranging from minimal bleeding or localized thrombosis to lethal or life-threatening hemorrhages or thrombotic events that sometimes occur concomitantly. Hemorrhagic events are the most common cause of death associated with APL coagulopathy, but thrombosis, a less recognized and probably underestimated life-threatening manifestation of the thrombo-hemorrhagic syndrome, is also a non-negligible cause of morbidity and mortality in patients with APL. In this article, we aim to discuss recent advances in the knowledge of pathogenesis, predictors of thrombo-hemorrhagic events, management of coagulopathy associated with APL and the controversial issues that still persist.
The risk of venous thromboembolism (VTE) is increased in patients with cancer and is greatest in those with cancers of the pancreas, stomach, brain, lung and ovary, late stage disease and in those undergoing treatment including chemotherapy, hormonal therapy, or surgery. VTE in patients with cancer is associated with a variety of adverse consequences including an increased risk of VTE recurrence, major bleeding, and early mortality. A VTE risk score for ambulatory patients receiving cancer chemotherapy has been extensively validated and has been used to select high risk patients for thromboprophylaxis trials. Several randomized controlled trials (RCTs) and meta-analyses of these trials have confirmed that LMWHs can significantly reduce the risk of VTE in patients with cancer. While the direct oral anticoagulants (DOACs) have been approved for the general population, previous guideline panels discouraged their use due to a lack of cancer-specific data. Recently RCTs for the treatment of established VTE in patients with cancer have demonstrated that the risk of recurrent VTE is lower while the risk of bleeding greater with DOACs compared to LMWH. Two thromboprophylaxis trials comparing low dose DOACs to placebo in high risk patients receiving cancer therapy have recently reported similar rates of VTE occurrence at 6 months in the control arms. A meta-analysis of the pooled results from these trials in higher risk ambulatory patients receiving cancer therapy confirmed a significant reduction in overall VTE incidence as well as pre-planned secondary outcomes on treatment. Several clinical practice guidelines addressing VTE in patients with malignant disease have been updated including those from the American Society of Clinical Oncology (ASCO). The addition of DOACs as an option for the management of VTE in patients with cancer is the latest major change to previous guidelines issued by these organizations. The updated recommendations from these guidelines are summarized in this review.Patients with multiple myeloma (MM) have an increased risk of venous thromboembolism (VTE) compared to the general population. This risk is highest during the first year of diagnosis and subsequently decreases over time. https://www.selleckchem.com/products/byl719.html Development of VTE in patients with MM is associated with inferior outcomes, with patients with VTE and MM having an increased risk of death compared to those with MM without VTE. Primary thromboprophylaxis has the potential to decrease risk of VTEksanfilippo@wustl.edu (K.M. Sanfilippo) in MM and improve outcomes. Current studies assessing thromboprophylaxis in MM excluded patients at high risk of VTE. A meta-analysis of trials of primary thromboprophylaxis in ambulatory cancer patients at high risk of VTE identified by use of a risk-prediction score found a reduction in risk of VTE with prophylaxis with no significant increase in risk of major bleeding. However, these trials contained relatively few patients with MM. Three clinical risk prediction scores are available to assess risk of VTE in MM 1) the International Myeloma Working Group (IMWG)/National Comprehensive Cancer Network (NCCN); 2) the SAVED score; and 3) the IMPEDE VTE score. The latter two have recently been shown to outperform the IMWG/ NCCN score for predicting VTE in MM. Biomarkers have the potential to improve prediction of VTE in patients with MM. Future research should focus on the addition of biomarkers to available risk scores in MM to improve discrimination in this high-risk patient population.A B S T R A C T Antithrombotic therapy (anticoagulation or antiplatelet therapy) is frequently prescribed in cancer patients for prior or new indications such as venous thromboembolism, secondary prevention of arterial thrombosis or atrial fibrillation. Therefore, it is not uncommon for thrombocytopenic cancer patients to have an indication for antithrombotic therapy. Thrombocytopenia does not reduce the risk of recurrent thrombosis. The bleeding risk with anticoagulation appears to increase when platelets are less then 50×109/L, but individual platelet counts are poor predictors of bleeding. Management options when platelets are less then 50×109/L include no change, temporarily withholding antithrombotic therapy, reducing dose, changing the regimen, and increasing the platelet transfusion threshold. There are currently no data on use of direct oral anticoagulants when platelets are below 50×109/L, and there is reason in restricting their use. Little is known on antiplatelet therapy in this setting, although recent data suggest the prognostic importance and apparent safety of aspirin in acute myocardial infarction and thrombocytopenia. This paper will review the evidence, guidelines, current practice and ongoing studies on anticoagulation and antiplatelet therapy in thrombocytopenic patients with cancer.Since the introduction of all-trans retinoic acid and, more recently, arsenic trioxide into the therapy of acute promyelocytic leukemia (APL), significant improvements in patient outcomes have been achieved, and this disease has become the most curable subtype of acute myeloid leukemia. However, while primary leukemia resistance has virtually disappeared, a sizable fraction of APL patients still die before or during induction therapy. Hemorrhagic death still remains the major problem during this early phase of treatment and, to a lesser extent, deaths due to infection, differentiation syndrome and other causes. Patients with APL typically present with a range of laboratory abnormalities consistent with the diagnosis of disseminated intravascular coagulation and hyperfibrinolysis. This APL-associated coagulopathy, as a result of a dysregulation of the hemostatic system due to the imbalance between procoagulant, anticoagulant and profibrinolytic mechanisms, may show a variety of clinical manifestations, ranging from minimal bleeding or localized thrombosis to lethal or life-threatening hemorrhages or thrombotic events that sometimes occur concomitantly. Hemorrhagic events are the most common cause of death associated with APL coagulopathy, but thrombosis, a less recognized and probably underestimated life-threatening manifestation of the thrombo-hemorrhagic syndrome, is also a non-negligible cause of morbidity and mortality in patients with APL. In this article, we aim to discuss recent advances in the knowledge of pathogenesis, predictors of thrombo-hemorrhagic events, management of coagulopathy associated with APL and the controversial issues that still persist.0 التعليقات 0 المشاركات 29 مشاهدة 0 معاينة -
57, 95% CI (-1.14-0.01), P-score = 0.72], in addition to achieve at the first time points [SMD = -0, 95% CI (-0.97 ̶ -0.16), P-score = 0.69], compared to placebo; however, lavender massage along with foot bath were found to be the most efficacious for anxiety treatment at the study endpoint [SMD = -1.10, 95% CI = (-7.41 ̶ 5.21), P-score = 0.65]. Furthermore, network meta-regression revealed that the duration of therapy influenced treatment, suggesting Silexan (oral lavender) 80 mg (first rank probability = .116) as the favorable option for anxiety in long-term treatment. CONCLUSIONS Lavender aromatherapy is, clinically, superior in short-duration, while Silexan (oral lavender) 80 mg is preferable for long-term treatment of anxiety. The growing proportion of senior citizens and the importance of encouraging active well-ageing behaviours explain the increasing efforts carried out by governments to develop exercise programmes particularly targeted to this group. The complexity associated with the running of these programmes and the resources committed make their quality assessment essential. The aim of the current paper is to validate and refine the use of the EFQM model in this context. A programme of a medium-sized municipality of the Centre region of Portugal was used as a case study to evaluate the adequacy and relevance of the EFQM model and to identify the strengths and weaknesses of the current programme based on the data collected from service users, instructors, municipal leaders and programme partners. High levels of customer satisfaction and loyalty, together with the clarity of programme mission and strategy emerged as main areas of strength. On the other hand, insufficient attention to the measurement of people satisfaction, as well as the leaders' failure of to show appreciation for the efforts developed by the programme instructors are key areas for improvement. Many dropout prevention programs have been developed and validated in the past decades. https://www.selleckchem.com/products/pexidartinib-plx3397.html Yet, little is known about the contextual factors influencing the implementation of these programs. Implementation processes, such as school principal leadership and governmental funding, have been identified for their influence on program implementation, but the mutual or dynamic influence of these processes is yet to be understood. This study examines the processes involved in the implementation of Check & Connect (C&C), a well-established targeted dropout prevention program validated in several countries that aims at promoting the development of a significant relationship between at-risk students and a mentor as a way to prevent school dropout. Semi-structured interviews were conducted with 12 mentors and coordinators directly involved in C&C implementation. Analyses were conducted in two subsequent steps thematic analyses first helped identify implementation processes described by respondents, and then synthetic case studies allowed us to build the implementation stories of distinct sites. This last step was conducted using the Planned Change Framework. This framework helped us to understand the complex dynamics of implementation processes in each site, which were associated with previously identified program outcomes, beyond implementation fidelity. Implications for future implementations of evidence-based programs in the school setting are discussed. DSM-5 includes criteria for an anxious distress specifier for major depressive disorder, and measures have been developed to assess these criteria. The validity of measures of the severity of anxious distress has been established in depressed patients. In the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project, we examined whether a severity measure of anxious distress was as valid as the Hamilton Anxiety Scale (HAMA) as a measure of the severity of anxiety in patients with generalized anxiety disorder (GAD). Eighty-five patients with GAD were interviewed by trained raters who administered the DSM-5 Anxious Distress Specifier Interview (DADSI), HAMA, and Hamilton Depression Rating Scale (HAMD). The patients completed self-report measures of depression, anxiety, and irritability. The DADSI and HAMA were significantly correlated (r 0.52, p less then .001). Both the DADSI and HAMA were more highly correlated with measures of anxiety than with measures of the other symptom domains. The HAMD was significantly more highly correlated with the HAMA than with the DADSI. Both measures were significantly correlated with measures of positive mental health, functioning, life satisfaction, and general well-being. Both measures were sensitive to change in response to treatment. Both the DADSI and HAMA were valid measures of anxiety severity in patients with GAD, though the HAMA was more highly confounded with the HAMD than the DADSI. The DADSI is briefer than the HAMA, and thus may be more practical to use in research studies as well as clinical practice. Nonsuicidal self-injury (NSSI) is a prevalent, concerning behavior among adolescents. Importantly, NSSI can serve a variety of functions. Some adolescents engage in NSSI to fulfill automatic or self-oriented functions (e.g., cutting to avoid internal negative states), whereas others engage in NSSI to serve social functions (e.g., cutting to communicate with others). This study tests whether self-reported reasons for engaging in NSSI, hereafter referred to as NSSI functions, predict NSSI thoughts and behaviors during and after hospitalization among adolescent psychiatric inpatients. Endorsement of both automatic and social NSSI functions, as well as positive and negative reinforcement subtypes, was assessed at hospital admission. Results showed that endorsement of overall automatic function predicted which adolescents engaged in NSSI behavior during hospitalization. Moreover, automatic and social functions showed distinct predictive patterns, such that automatic functions corresponded to greater likelihood of NSSI-related thoughts and behaviors whereas social functions mainly corresponded to reduced likelihood of NSSI-related outcomes. Of note, NSSI functions were less predictive of NSSI-related outcomes after hospital discharge. These findings suggest that identifying adolescent inpatients' reasons for NSSI engagement may meaningfully distinguish those at higher risk (and those at lower risk) of NSSI persistence during their hospital stay.
57, 95% CI (-1.14-0.01), P-score = 0.72], in addition to achieve at the first time points [SMD = -0, 95% CI (-0.97 ̶ -0.16), P-score = 0.69], compared to placebo; however, lavender massage along with foot bath were found to be the most efficacious for anxiety treatment at the study endpoint [SMD = -1.10, 95% CI = (-7.41 ̶ 5.21), P-score = 0.65]. Furthermore, network meta-regression revealed that the duration of therapy influenced treatment, suggesting Silexan (oral lavender) 80 mg (first rank probability = .116) as the favorable option for anxiety in long-term treatment. CONCLUSIONS Lavender aromatherapy is, clinically, superior in short-duration, while Silexan (oral lavender) 80 mg is preferable for long-term treatment of anxiety. The growing proportion of senior citizens and the importance of encouraging active well-ageing behaviours explain the increasing efforts carried out by governments to develop exercise programmes particularly targeted to this group. The complexity associated with the running of these programmes and the resources committed make their quality assessment essential. The aim of the current paper is to validate and refine the use of the EFQM model in this context. A programme of a medium-sized municipality of the Centre region of Portugal was used as a case study to evaluate the adequacy and relevance of the EFQM model and to identify the strengths and weaknesses of the current programme based on the data collected from service users, instructors, municipal leaders and programme partners. High levels of customer satisfaction and loyalty, together with the clarity of programme mission and strategy emerged as main areas of strength. On the other hand, insufficient attention to the measurement of people satisfaction, as well as the leaders' failure of to show appreciation for the efforts developed by the programme instructors are key areas for improvement. Many dropout prevention programs have been developed and validated in the past decades. https://www.selleckchem.com/products/pexidartinib-plx3397.html Yet, little is known about the contextual factors influencing the implementation of these programs. Implementation processes, such as school principal leadership and governmental funding, have been identified for their influence on program implementation, but the mutual or dynamic influence of these processes is yet to be understood. This study examines the processes involved in the implementation of Check & Connect (C&C), a well-established targeted dropout prevention program validated in several countries that aims at promoting the development of a significant relationship between at-risk students and a mentor as a way to prevent school dropout. Semi-structured interviews were conducted with 12 mentors and coordinators directly involved in C&C implementation. Analyses were conducted in two subsequent steps thematic analyses first helped identify implementation processes described by respondents, and then synthetic case studies allowed us to build the implementation stories of distinct sites. This last step was conducted using the Planned Change Framework. This framework helped us to understand the complex dynamics of implementation processes in each site, which were associated with previously identified program outcomes, beyond implementation fidelity. Implications for future implementations of evidence-based programs in the school setting are discussed. DSM-5 includes criteria for an anxious distress specifier for major depressive disorder, and measures have been developed to assess these criteria. The validity of measures of the severity of anxious distress has been established in depressed patients. In the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project, we examined whether a severity measure of anxious distress was as valid as the Hamilton Anxiety Scale (HAMA) as a measure of the severity of anxiety in patients with generalized anxiety disorder (GAD). Eighty-five patients with GAD were interviewed by trained raters who administered the DSM-5 Anxious Distress Specifier Interview (DADSI), HAMA, and Hamilton Depression Rating Scale (HAMD). The patients completed self-report measures of depression, anxiety, and irritability. The DADSI and HAMA were significantly correlated (r 0.52, p less then .001). Both the DADSI and HAMA were more highly correlated with measures of anxiety than with measures of the other symptom domains. The HAMD was significantly more highly correlated with the HAMA than with the DADSI. Both measures were significantly correlated with measures of positive mental health, functioning, life satisfaction, and general well-being. Both measures were sensitive to change in response to treatment. Both the DADSI and HAMA were valid measures of anxiety severity in patients with GAD, though the HAMA was more highly confounded with the HAMD than the DADSI. The DADSI is briefer than the HAMA, and thus may be more practical to use in research studies as well as clinical practice. Nonsuicidal self-injury (NSSI) is a prevalent, concerning behavior among adolescents. Importantly, NSSI can serve a variety of functions. Some adolescents engage in NSSI to fulfill automatic or self-oriented functions (e.g., cutting to avoid internal negative states), whereas others engage in NSSI to serve social functions (e.g., cutting to communicate with others). This study tests whether self-reported reasons for engaging in NSSI, hereafter referred to as NSSI functions, predict NSSI thoughts and behaviors during and after hospitalization among adolescent psychiatric inpatients. Endorsement of both automatic and social NSSI functions, as well as positive and negative reinforcement subtypes, was assessed at hospital admission. Results showed that endorsement of overall automatic function predicted which adolescents engaged in NSSI behavior during hospitalization. Moreover, automatic and social functions showed distinct predictive patterns, such that automatic functions corresponded to greater likelihood of NSSI-related thoughts and behaviors whereas social functions mainly corresponded to reduced likelihood of NSSI-related outcomes. Of note, NSSI functions were less predictive of NSSI-related outcomes after hospital discharge. These findings suggest that identifying adolescent inpatients' reasons for NSSI engagement may meaningfully distinguish those at higher risk (and those at lower risk) of NSSI persistence during their hospital stay.0 التعليقات 0 المشاركات 32 مشاهدة 0 معاينة
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