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In contrast, shorter and less abundant reads were recovered from the dicyemid mitochondrial RNAs (mtRNAs). Even the longest read was 307 bp covering only a part of a minicircle. This study revealed significantly different modes of the mitochondrial transcription between a mesozoan and the host. Our approach to perform direct RNA-sequencing combined with the poly(A)-tailing reaction can be an effective method to fully capture non-poly(A) transcripts in a wide range of organisms. While significant advancements have been made in the available therapies for metastatic non-small cell lung cancer (NSCLC), acquired resistance remains a major barrier to treatment. We have not yet achieved the ability to cure advanced NSCLC with systemic therapy, despite our growing understanding of many of the oncogenic drivers of this disease. Rather, the emergence of drug-tolerant and drug-resistant cells remains the rule, even in the face of increasingly potent targeted therapies. In this review, we provide a broad overview of the mechanisms of resistance to targeted therapy that have been demonstrated across molecular subtypes of NSCLC, highlighting the dynamic interplay between driver oncogene, bypass signaling pathways, shifting cellular phenotypes, and surrounding tumor microenvironment. From advances in the knowledge of the immune system, it is emerging that the specialized functions displayed by macrophages during the course of an immune response are supported by specific and dynamically-connected metabolic programs. The study of immunometabolism is demonstrating that metabolic adaptations play a critical role in modulating inflammation and, conversely, inflammation deeply influences the acquisition of specific metabolic settings.This strict connection has been proven to be crucial for the execution of defined immune functional programs and it is now under investigation with respect to several human disorders, such as diabetes, sepsis, cancer, and autoimmunity. The abnormal remodelling of the metabolic pathways in macrophages is now emerging as both marker of disease and potential target of therapeutic intervention. By focusing on key pathological conditions, namely obesity and diabetes, rheumatoid arthritis, atherosclerosis and cancer, we will review the metabolic targets suitable for therapeutic intervention in macrophages. In addition, we will discuss the major obstacles and challenges related to the development of therapeutic strategies for a pharmacological targeting of macrophage's metabolism. Cisplatin is one of the most widely used platinum-based anticancer chemotherapeutic drugs. https://www.selleckchem.com/products/740-y-p-pdgfr-740y-p.html However, its low solubility, serious side effects and the development of cisplatin resistance limit its further use in the clinic. Controlling the delivery and release of cisplatin at the targeted site efficiently is a meaningful way to overcome these undesirable side effects of cisplatin. Herein, a tumor targeted and stimuli responsive nano-delivery system for cisplatin was constructed using branched polyethyleneimine (BPEI) as the backbone, disulfide bond as the redox-responsive covalent linker and hyaluronic acid (HA) as targeting recognition unit which can bind selectively to the receptor of CD44, which is highly expressed on the A549 tumor cells. The cisplatin-polyethyleneimine conjugate BPEI-SS-Pt was prepared and the drug loading of cisplatin was up to 32.66 ± 0.06%. After optimized the coating weight ratio of HA and BPEI-SS-Pt, the nanoparticle delivery system HA-(BPEI-SS-Pt)-1/4 outperformed with smaller particle size of 159.0 ± 21.0 nm, narrow polydispersity index (PDI) of 0.069 ± 0.022 and higher cisplatin loading of 29.23 ± 0.18%, showing specific tumor-targeting ability and redox-responsive drug release manner. Moreover, for the treatment of cancer in vivo, it achieved more effective antitumor performance along with minor side effects and systemic toxicity compared with cisplatin which is of great significance for the chemotherapeutic drug in the clinic. PURPOSE To perform a systematic review of the literature describing outcomes, surgical procedures, and rates of arthroplasty conversion following arthroscopic debridement of symptomatic primary glenohumeral osteoarthritis (GHOA). METHODS The Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, and Ovid MEDLINE were queried. Articles without sufficiently detailed descriptions of the debridement procedure, those primarily describing cartilage resurfacing procedures, or those that did not report any postoperative outcomes were excluded. Study design, patient demographics, operative details, imaging findings, patient-reported outcomes, and rates of conversion to arthroplasty were compiled and reported. Assessment of bias was reported using the Methodological Index for Non-randomized Studies (MINORS) criteria. RESULTS A total of 8 studies including 371 patients (382 shoulders) were included. Patient samples sizes ranged from 8 patients (9 shoulders) to 98 patlear, with studies including longer duration of follow-up demonstrating potential regression of symptom relief and increased rates of conversion to arthroplasty. PURPOSE (1) To determine whether EUA and/or MRI is an accurate means for determining patient selection for a selective bundle reconstruction. (2) Determine whether the preoperative clinical assessment correlates with the arthroscopic examination. (3) Examine histologically whether a partial ACL tear is truly partial in terms of vascular insult METHODS This prospective, non-randomized cohort study included 95 patients who underwent primary ACL reconstruction from Jan 2013 to May 2014. All patients had an EUA, MRI, and arthroscopic evaluation. In patients with partial ACL tears, the intact bundle was resected and sent for histologic examination. Chi-squared test was used to compare EUA and MRI in the detection of partial tears RESULTS Of the 95 patients included, 40 patients (42%) had EUA consistent with a partial ACL tear. 22 patients (23%) had MRI's interpreted as partial ACL tears. In only 11 patients (12%), arthroscopic exam confirmed a partial ACL tear. The sensitivity and specificity of EUA and MRI in the detection of partial ACL tears were 100%, 65% and 90.
In contrast, shorter and less abundant reads were recovered from the dicyemid mitochondrial RNAs (mtRNAs). Even the longest read was 307 bp covering only a part of a minicircle. This study revealed significantly different modes of the mitochondrial transcription between a mesozoan and the host. Our approach to perform direct RNA-sequencing combined with the poly(A)-tailing reaction can be an effective method to fully capture non-poly(A) transcripts in a wide range of organisms. While significant advancements have been made in the available therapies for metastatic non-small cell lung cancer (NSCLC), acquired resistance remains a major barrier to treatment. We have not yet achieved the ability to cure advanced NSCLC with systemic therapy, despite our growing understanding of many of the oncogenic drivers of this disease. Rather, the emergence of drug-tolerant and drug-resistant cells remains the rule, even in the face of increasingly potent targeted therapies. In this review, we provide a broad overview of the mechanisms of resistance to targeted therapy that have been demonstrated across molecular subtypes of NSCLC, highlighting the dynamic interplay between driver oncogene, bypass signaling pathways, shifting cellular phenotypes, and surrounding tumor microenvironment. From advances in the knowledge of the immune system, it is emerging that the specialized functions displayed by macrophages during the course of an immune response are supported by specific and dynamically-connected metabolic programs. The study of immunometabolism is demonstrating that metabolic adaptations play a critical role in modulating inflammation and, conversely, inflammation deeply influences the acquisition of specific metabolic settings.This strict connection has been proven to be crucial for the execution of defined immune functional programs and it is now under investigation with respect to several human disorders, such as diabetes, sepsis, cancer, and autoimmunity. The abnormal remodelling of the metabolic pathways in macrophages is now emerging as both marker of disease and potential target of therapeutic intervention. By focusing on key pathological conditions, namely obesity and diabetes, rheumatoid arthritis, atherosclerosis and cancer, we will review the metabolic targets suitable for therapeutic intervention in macrophages. In addition, we will discuss the major obstacles and challenges related to the development of therapeutic strategies for a pharmacological targeting of macrophage's metabolism. Cisplatin is one of the most widely used platinum-based anticancer chemotherapeutic drugs. https://www.selleckchem.com/products/740-y-p-pdgfr-740y-p.html However, its low solubility, serious side effects and the development of cisplatin resistance limit its further use in the clinic. Controlling the delivery and release of cisplatin at the targeted site efficiently is a meaningful way to overcome these undesirable side effects of cisplatin. Herein, a tumor targeted and stimuli responsive nano-delivery system for cisplatin was constructed using branched polyethyleneimine (BPEI) as the backbone, disulfide bond as the redox-responsive covalent linker and hyaluronic acid (HA) as targeting recognition unit which can bind selectively to the receptor of CD44, which is highly expressed on the A549 tumor cells. The cisplatin-polyethyleneimine conjugate BPEI-SS-Pt was prepared and the drug loading of cisplatin was up to 32.66 ± 0.06%. After optimized the coating weight ratio of HA and BPEI-SS-Pt, the nanoparticle delivery system HA-(BPEI-SS-Pt)-1/4 outperformed with smaller particle size of 159.0 ± 21.0 nm, narrow polydispersity index (PDI) of 0.069 ± 0.022 and higher cisplatin loading of 29.23 ± 0.18%, showing specific tumor-targeting ability and redox-responsive drug release manner. Moreover, for the treatment of cancer in vivo, it achieved more effective antitumor performance along with minor side effects and systemic toxicity compared with cisplatin which is of great significance for the chemotherapeutic drug in the clinic. PURPOSE To perform a systematic review of the literature describing outcomes, surgical procedures, and rates of arthroplasty conversion following arthroscopic debridement of symptomatic primary glenohumeral osteoarthritis (GHOA). METHODS The Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, and Ovid MEDLINE were queried. Articles without sufficiently detailed descriptions of the debridement procedure, those primarily describing cartilage resurfacing procedures, or those that did not report any postoperative outcomes were excluded. Study design, patient demographics, operative details, imaging findings, patient-reported outcomes, and rates of conversion to arthroplasty were compiled and reported. Assessment of bias was reported using the Methodological Index for Non-randomized Studies (MINORS) criteria. RESULTS A total of 8 studies including 371 patients (382 shoulders) were included. Patient samples sizes ranged from 8 patients (9 shoulders) to 98 patlear, with studies including longer duration of follow-up demonstrating potential regression of symptom relief and increased rates of conversion to arthroplasty. PURPOSE (1) To determine whether EUA and/or MRI is an accurate means for determining patient selection for a selective bundle reconstruction. (2) Determine whether the preoperative clinical assessment correlates with the arthroscopic examination. (3) Examine histologically whether a partial ACL tear is truly partial in terms of vascular insult METHODS This prospective, non-randomized cohort study included 95 patients who underwent primary ACL reconstruction from Jan 2013 to May 2014. All patients had an EUA, MRI, and arthroscopic evaluation. In patients with partial ACL tears, the intact bundle was resected and sent for histologic examination. Chi-squared test was used to compare EUA and MRI in the detection of partial tears RESULTS Of the 95 patients included, 40 patients (42%) had EUA consistent with a partial ACL tear. 22 patients (23%) had MRI's interpreted as partial ACL tears. In only 11 patients (12%), arthroscopic exam confirmed a partial ACL tear. The sensitivity and specificity of EUA and MRI in the detection of partial ACL tears were 100%, 65% and 90.0 Comments 0 Shares 353 Views 0 ReviewsPlease log in to like, share and comment! -
few previously available phytochemical data have good antiprotozoal activity and could be a starting point for subsequent promising work. Metabolomic approach appears to be a smart, quick but still limited methodology to identify compounds with high probability of biological activity.
Ashwagandha (Withania somnifera (L.) Dunal.) is long known for its sleep-inducing effects. Ashwagandha can be proposed as an alternative to the recommended present treatments for insomnia. This study aimed to evaluate the pharmacological effect of Ashwagandha root extract on sleep in healthy subjects and also in the subjects having insomnia.
We performed a randomized, parallel-group, stratified design, placebo-controlled study. A total of 80 eligible participants, 40 in Arm-A (healthy) and 40 in Arm-B (insomnia) were assigned to two groups, either Ashwagandha or placebo and studied for 8-weeks. The assessment was done based on the sleep parameters (Sleep Onset Latency, Total Sleep Time, Wake After Sleep Onset, Total time in bed, and Sleep Efficiency), Pittsburgh Sleep Quality Index and Hamilton Anxiety scale-A questionnaire, mental alertness on rising assessment, and sleep quality questionnaire. Safety and adverse events along with the concomitant medication were also assessed.
In both healthy and insomhe study results except for the HAM-A and the mental alertness scoresn the healthy subject group.
The present study confirms that Ashwagandha root extract can improve sleep quality and can help in managing insomnia. Ashwagandha root extract was well tolerated by all the participants irrespective of their health condition and age. Additional clinical trials are required to generalize the outcome.
The present study confirms that Ashwagandha root extract can improve sleep quality and can help in managing insomnia. Ashwagandha root extract was well tolerated by all the participants irrespective of their health condition and age. Additional clinical trials are required to generalize the outcome.
The extracts of Jerusalem thorn fruits (JT-FE) have been commonly used for the treatment of diabetes mellitus in Turkey.
In this study, it is aimed to investigate the effects of the JT-FE, prepared by decoction, on blood glucose, insulin and glycated haemoglobin levels of diabetic rats induced with streptozotocin (STZ). Hypoglycemic activity of the extracts was examined in streptozotocin-induced diabetic rats.
For this purpose, pre-prandial blood sugar, insulin and glycated hemoglobin levels were measured. To investigate active substances that were responsible for the antidiabetic activity, phytochemical analysis was carried out with optimized and validated LC-MS/MS method using 53 phytochemicals in JT-FE. In addition, ICP-OES analysis was performed to determine the mineral content.
The findings of the study demonstrate that when insulin and JT-FE applied groups were compared with the diabetic control group, their blood sugar and glycated hemoglobin levels were seen to statistically decrease (p<0,0 decoction, is rich in phenolic and mineral content and strong in antihyperglycemic activity. That's why Jerusalem thorn fruits can be a useful antidiabetic phytotherapy agent.
The nuclear location of miRNAs has been known for more than a decade, but the exact function of miRNAs in the nucleus has not been fully elucidated. We previously discovered that intranuclear miR-552-3p has an inhibitory role on gene transcription and contains a particular AGGTCA-like sequence, the cis-elements of the NR1 subfamily of nuclear receptors. Here, we aim to explore the potential effect of miR-552-3p and its AGGTCA-like sequence on NR1s and its possible application in improving hepatic glycolipid metabolism.
RNA-seq, mass spectrometry, and bioinformatics analysis were used to reveal the possible pathways influenced by miR-552-3p. HFHFr **** and db/db **** transfected with AAV2/8-miR-552-3p were established to investigate the invivo effects of miR-552-3p on hepatic glycolipid metabolism. Fluorescence resonance energy transfer, pull-down, electrophoretic mobility shift, and chromatin immunoprecipitation assays were performed to explore the mechanism by which miR-552-3p regulates NR1s. RT-PCR was ases, which have become a major public health concern worldwide, are triggered by abnormalities in lipid and glucose metabolism. Herein, we show that miR-552-3p has the ability to ameliorate hepatic glycolipid metabolic diseases by modulating the transcriptional activities of LXRα and FXR in the nucleus. These findings provide evidence that miR-552-3p may serve as a potential therapeutic target.
Glycolipid metabolic diseases, which have become a major public health concern worldwide, are triggered by abnormalities in lipid and glucose metabolism. https://www.selleckchem.com/products/jw74.html Herein, we show that miR-552-3p has the ability to ameliorate hepatic glycolipid metabolic diseases by modulating the transcriptional activities of LXRα and FXR in the nucleus. These findings provide evidence that miR-552-3p may serve as a potential therapeutic target.
Despite the clinical and genetic significance of macrotrabecular-massive hepatocellular carcinoma (MTM-HCC), its characteristics on imaging have not been described. This study aimed to characterise MTM-HCC on gadoxetic acid-enhanced MRI and to evaluate the diagnostic accuracy and prognostic value of these imaging characteristics.
We enrolled 3 independent cohorts from 2 tertiary care centres. The 3 cohorts consisted of a total of 476 patients who underwent gadoxetic acid-enhanced MRI and surgical resection for treatment-naïve single HCCs. Independent review of histopathology and MRI by 2 reviewers was performed for each cohort, and inter-reader agreement was evaluated. Based on the result of MRI review in the training cohort (cohort 1), we developed 2 diagnostic criteria for MTM-HCC and evaluated their prognostic significance. The diagnostic performance and prognostic significance were validated in 2 validation cohorts (cohorts 2 and 3).
We developed 2 diagnostic MRI criteria (MRIC) for MTM-HCC MRIC-1, eveloped imaging criteria based on liver MRI that could be used for the non-invasive diagnosis of MTM-HCC. HCCs showing imaging findings of MTM-HCC were associated with poor outcomes after hepatic resection.
Macrotrabecular-massive hepatocellular carcinoma (MTM-HCC) is a histopathologic subtype of HCC characterised by aggressive biological behaviour and poor prognosis. We developed imaging criteria based on liver MRI that could be used for the non-invasive diagnosis of MTM-HCC. HCCs showing imaging findings of MTM-HCC were associated with poor outcomes after hepatic resection.
few previously available phytochemical data have good antiprotozoal activity and could be a starting point for subsequent promising work. Metabolomic approach appears to be a smart, quick but still limited methodology to identify compounds with high probability of biological activity. Ashwagandha (Withania somnifera (L.) Dunal.) is long known for its sleep-inducing effects. Ashwagandha can be proposed as an alternative to the recommended present treatments for insomnia. This study aimed to evaluate the pharmacological effect of Ashwagandha root extract on sleep in healthy subjects and also in the subjects having insomnia. We performed a randomized, parallel-group, stratified design, placebo-controlled study. A total of 80 eligible participants, 40 in Arm-A (healthy) and 40 in Arm-B (insomnia) were assigned to two groups, either Ashwagandha or placebo and studied for 8-weeks. The assessment was done based on the sleep parameters (Sleep Onset Latency, Total Sleep Time, Wake After Sleep Onset, Total time in bed, and Sleep Efficiency), Pittsburgh Sleep Quality Index and Hamilton Anxiety scale-A questionnaire, mental alertness on rising assessment, and sleep quality questionnaire. Safety and adverse events along with the concomitant medication were also assessed. In both healthy and insomhe study results except for the HAM-A and the mental alertness scoresn the healthy subject group. The present study confirms that Ashwagandha root extract can improve sleep quality and can help in managing insomnia. Ashwagandha root extract was well tolerated by all the participants irrespective of their health condition and age. Additional clinical trials are required to generalize the outcome. The present study confirms that Ashwagandha root extract can improve sleep quality and can help in managing insomnia. Ashwagandha root extract was well tolerated by all the participants irrespective of their health condition and age. Additional clinical trials are required to generalize the outcome. The extracts of Jerusalem thorn fruits (JT-FE) have been commonly used for the treatment of diabetes mellitus in Turkey. In this study, it is aimed to investigate the effects of the JT-FE, prepared by decoction, on blood glucose, insulin and glycated haemoglobin levels of diabetic rats induced with streptozotocin (STZ). Hypoglycemic activity of the extracts was examined in streptozotocin-induced diabetic rats. For this purpose, pre-prandial blood sugar, insulin and glycated hemoglobin levels were measured. To investigate active substances that were responsible for the antidiabetic activity, phytochemical analysis was carried out with optimized and validated LC-MS/MS method using 53 phytochemicals in JT-FE. In addition, ICP-OES analysis was performed to determine the mineral content. The findings of the study demonstrate that when insulin and JT-FE applied groups were compared with the diabetic control group, their blood sugar and glycated hemoglobin levels were seen to statistically decrease (p<0,0 decoction, is rich in phenolic and mineral content and strong in antihyperglycemic activity. That's why Jerusalem thorn fruits can be a useful antidiabetic phytotherapy agent. The nuclear location of miRNAs has been known for more than a decade, but the exact function of miRNAs in the nucleus has not been fully elucidated. We previously discovered that intranuclear miR-552-3p has an inhibitory role on gene transcription and contains a particular AGGTCA-like sequence, the cis-elements of the NR1 subfamily of nuclear receptors. Here, we aim to explore the potential effect of miR-552-3p and its AGGTCA-like sequence on NR1s and its possible application in improving hepatic glycolipid metabolism. RNA-seq, mass spectrometry, and bioinformatics analysis were used to reveal the possible pathways influenced by miR-552-3p. HFHFr mice and db/db mice transfected with AAV2/8-miR-552-3p were established to investigate the invivo effects of miR-552-3p on hepatic glycolipid metabolism. Fluorescence resonance energy transfer, pull-down, electrophoretic mobility shift, and chromatin immunoprecipitation assays were performed to explore the mechanism by which miR-552-3p regulates NR1s. RT-PCR was ases, which have become a major public health concern worldwide, are triggered by abnormalities in lipid and glucose metabolism. Herein, we show that miR-552-3p has the ability to ameliorate hepatic glycolipid metabolic diseases by modulating the transcriptional activities of LXRα and FXR in the nucleus. These findings provide evidence that miR-552-3p may serve as a potential therapeutic target. Glycolipid metabolic diseases, which have become a major public health concern worldwide, are triggered by abnormalities in lipid and glucose metabolism. https://www.selleckchem.com/products/jw74.html Herein, we show that miR-552-3p has the ability to ameliorate hepatic glycolipid metabolic diseases by modulating the transcriptional activities of LXRα and FXR in the nucleus. These findings provide evidence that miR-552-3p may serve as a potential therapeutic target. Despite the clinical and genetic significance of macrotrabecular-massive hepatocellular carcinoma (MTM-HCC), its characteristics on imaging have not been described. This study aimed to characterise MTM-HCC on gadoxetic acid-enhanced MRI and to evaluate the diagnostic accuracy and prognostic value of these imaging characteristics. We enrolled 3 independent cohorts from 2 tertiary care centres. The 3 cohorts consisted of a total of 476 patients who underwent gadoxetic acid-enhanced MRI and surgical resection for treatment-naïve single HCCs. Independent review of histopathology and MRI by 2 reviewers was performed for each cohort, and inter-reader agreement was evaluated. Based on the result of MRI review in the training cohort (cohort 1), we developed 2 diagnostic criteria for MTM-HCC and evaluated their prognostic significance. The diagnostic performance and prognostic significance were validated in 2 validation cohorts (cohorts 2 and 3). We developed 2 diagnostic MRI criteria (MRIC) for MTM-HCC MRIC-1, eveloped imaging criteria based on liver MRI that could be used for the non-invasive diagnosis of MTM-HCC. HCCs showing imaging findings of MTM-HCC were associated with poor outcomes after hepatic resection. Macrotrabecular-massive hepatocellular carcinoma (MTM-HCC) is a histopathologic subtype of HCC characterised by aggressive biological behaviour and poor prognosis. We developed imaging criteria based on liver MRI that could be used for the non-invasive diagnosis of MTM-HCC. HCCs showing imaging findings of MTM-HCC were associated with poor outcomes after hepatic resection.0 Comments 0 Shares 85 Views 0 Reviews -
Herpes simplex encephalomyelitis (HSE) is a rare disease with a high mortality rate. Correct diagnosis is established on the basis of the combination of the clinical and investigative features. Unfortunately, precise diagnosis remains difficult due to several clinical similarities and false negative or inconclusive results of diagnostic tests. Here, we present two cases of HSE together with the morphological and ultrastructural picture. The first case was a 45-year-old man with acute symptoms of encephalitis, and the other one was a 28-year-old woman presenting subacute encephalomyelitis. Both cases had negative serologic and molecular results for Herpes simplex in the blood and cerebrospinal fluid. Brain and spinal cord samples taken from both cases were stained typically with histological and immunohistochemical methods and small tissue fragments were examined with the transmission electron microscope (TEM). Microscopic examination confirmed viral encephalomyelitis in both cases. An electron micrograph showed typical intranuclear viral particles inside of damaged neurons, which together with topography of brain and spinal cord changes suggest HHV-1/HHV-2 in the first case and/or HHV-3 in the other case. Thus, morphological and ultrastructural examinations may be a useful tool to set up correct diagnosis and help to determine the pathogenic factor in patients suspected of viral encephalomyelitis.
Meningiomas comprises of awide variety of histological entities with heterogeneous biological behaviour and prognosis. The plethora of genetic data are yet to produce relevant biomarkers for routine use. In contrast, epigenetic alterations are less elucidated.
The expression of the key molecules involved in the two principal epigenetic systems, i.e. DNA methylation (DNA methyltransferases [DNMT-1, -3A and -3B]) and histone modification (Enhancer of Zeste homolog-2 [EZH2] and trimethyl histone-3 [H3K27me3]) were assessed in 149 cases of meningiomas (grade I- 102, grade II - 47) by immunohistochemistry.
Immunopositivity for EZH2 (38.3% vs. 6.0%) and negativity for H3K27me3 (10.6% vs. 1.0%) were significantly more common in grade II tumours. Both were associated with significantly higher proliferative activity. The majority of the cases of both grades showed expression of all three DNMTs. However, high expression of DNMT-1 was significantly more common in grade II tumours (87.8% vs. 66.2%). Expression of EZH2 and loss of H3K27me3 were associated with significantly shorter progression-free survival (hazard ratio [HR] = 4.07 and 0.24, respectively).
The key epigenetic regulators play important roles in the pathobiology of meningiomas. EZH2 positivity and H3K27me3 negativity are associated with aggressive tumour-biology and poor prognosis. Both these markers can easily be assessed by immunohistochemistry and can be incorporated in routine practice.
The key epigenetic regulators play important roles in the pathobiology of meningiomas. EZH2 positivity and H3K27me3 negativity are associated with aggressive tumour-biology and poor prognosis. Both these markers can easily be assessed by immunohistochemistry and can be incorporated in routine practice.Nowadays molecular investigations have a significant impact on the understanding of primary brain tumour biology,as well as on their classification and progress in the treatment modalities. Among novel type of biomarkers with potential therapeutic value, microRNAs (miRNAs) are considered in some cases. miRNAs are small molecules regu-lating gene expression, including genes encoding key proteins involved in signalling pathways responsible for growth and cell survival during tumour formation. Incorrectly hyperactivated pathways implicated in brain tumour development are inter alia the PI3K/AKT/mTOR and RAS/MAPK/ERK cascades associated with worse prognosis and decreased patient survival. This work presents relationships between changes in the expression of individual miRNAs and the genes involved in the regulation of PI3K/AKT/mTOR and RAS/MAPK/ERK signalling pathways in primary brain tumours. Herein we present the preliminary results of miR-17-5p and miR-20a (key representatives of the miR-17-92 oncogenic cluster) expression analysis and their connection with signalling pathway activation in two of the most frequent paediatric tumours medulloblastoma and ependymoma. https://www.selleckchem.com/products/vx-661.html Our study was performed using the microarray and qPCR techniques and showed PI3K/AKT/mTOR and RAS/MAPK/ERK among the forefront of the list of pathways with the largest number of genes involved in their activation compared to the control. Predicted target analysis indicated the agents from miR-17-92 cluster within miRNAs regulating activity of PI3K/AKT/mTOR and RAS/MAPK/ERK deregulated genes. The expression level of key representatives of the oncogenic cluster, miR-17-5p, and miR-20a, increased with the WHO grade of the analysed cases; the highest levels were found in medulloblastomas.Lipopolysaccharide (LPS) is a potent immunogen when administered locally and/or systemically. The peripheral immunization with LPS could contribute to the progression of neurological diseases because a strong link between neuroinflammation and dopaminergic degeneration has been found. The switch between the survival and neuronal death in substantia nigra could be related to M1 (neurotoxic) and M2 (neuroprotective) microglia phenotypes. In this review, we present the current findings about microglia roles, biomarkers, and natural or synthetic immune modulators determined in the LPS-based murine model.A hypothesis is proposed to explain the pathogenesis of neurodegenerative disease and the diversity of its phenotypes. The hypothesis is based on seven main propositions 1) neurodegenerative disease is associated with multiple risk factors, 2) age is the most important of the risk factors, 3) aging differentially affects neuroanatomical pathways, 4) degeneration of these pathways results in the formation of pathogenic proteins, 5) pathogenic proteins spread along anatomical pathways, 6) the phenotypes of familial and sporadic forms of disease are similar and 7) neurodegenerative disease is characterised by heterogeneity, overlapping phenotypes, and multiple pathology. It is hypothesised that most cases of neurodegenerative disease are multifactorial in which interactions between external environmental and internal genetic risk factors act cumulatively over a lifetime to determine the 'allostatic load' of an individual. The allostatic load determines the rate of neural aging and results in the differential breakdown of neuro-anatomical pathways influenced by their relative use or disuse during life.
Herpes simplex encephalomyelitis (HSE) is a rare disease with a high mortality rate. Correct diagnosis is established on the basis of the combination of the clinical and investigative features. Unfortunately, precise diagnosis remains difficult due to several clinical similarities and false negative or inconclusive results of diagnostic tests. Here, we present two cases of HSE together with the morphological and ultrastructural picture. The first case was a 45-year-old man with acute symptoms of encephalitis, and the other one was a 28-year-old woman presenting subacute encephalomyelitis. Both cases had negative serologic and molecular results for Herpes simplex in the blood and cerebrospinal fluid. Brain and spinal cord samples taken from both cases were stained typically with histological and immunohistochemical methods and small tissue fragments were examined with the transmission electron microscope (TEM). Microscopic examination confirmed viral encephalomyelitis in both cases. An electron micrograph showed typical intranuclear viral particles inside of damaged neurons, which together with topography of brain and spinal cord changes suggest HHV-1/HHV-2 in the first case and/or HHV-3 in the other case. Thus, morphological and ultrastructural examinations may be a useful tool to set up correct diagnosis and help to determine the pathogenic factor in patients suspected of viral encephalomyelitis. Meningiomas comprises of awide variety of histological entities with heterogeneous biological behaviour and prognosis. The plethora of genetic data are yet to produce relevant biomarkers for routine use. In contrast, epigenetic alterations are less elucidated. The expression of the key molecules involved in the two principal epigenetic systems, i.e. DNA methylation (DNA methyltransferases [DNMT-1, -3A and -3B]) and histone modification (Enhancer of Zeste homolog-2 [EZH2] and trimethyl histone-3 [H3K27me3]) were assessed in 149 cases of meningiomas (grade I- 102, grade II - 47) by immunohistochemistry. Immunopositivity for EZH2 (38.3% vs. 6.0%) and negativity for H3K27me3 (10.6% vs. 1.0%) were significantly more common in grade II tumours. Both were associated with significantly higher proliferative activity. The majority of the cases of both grades showed expression of all three DNMTs. However, high expression of DNMT-1 was significantly more common in grade II tumours (87.8% vs. 66.2%). Expression of EZH2 and loss of H3K27me3 were associated with significantly shorter progression-free survival (hazard ratio [HR] = 4.07 and 0.24, respectively). The key epigenetic regulators play important roles in the pathobiology of meningiomas. EZH2 positivity and H3K27me3 negativity are associated with aggressive tumour-biology and poor prognosis. Both these markers can easily be assessed by immunohistochemistry and can be incorporated in routine practice. The key epigenetic regulators play important roles in the pathobiology of meningiomas. EZH2 positivity and H3K27me3 negativity are associated with aggressive tumour-biology and poor prognosis. Both these markers can easily be assessed by immunohistochemistry and can be incorporated in routine practice.Nowadays molecular investigations have a significant impact on the understanding of primary brain tumour biology,as well as on their classification and progress in the treatment modalities. Among novel type of biomarkers with potential therapeutic value, microRNAs (miRNAs) are considered in some cases. miRNAs are small molecules regu-lating gene expression, including genes encoding key proteins involved in signalling pathways responsible for growth and cell survival during tumour formation. Incorrectly hyperactivated pathways implicated in brain tumour development are inter alia the PI3K/AKT/mTOR and RAS/MAPK/ERK cascades associated with worse prognosis and decreased patient survival. This work presents relationships between changes in the expression of individual miRNAs and the genes involved in the regulation of PI3K/AKT/mTOR and RAS/MAPK/ERK signalling pathways in primary brain tumours. Herein we present the preliminary results of miR-17-5p and miR-20a (key representatives of the miR-17-92 oncogenic cluster) expression analysis and their connection with signalling pathway activation in two of the most frequent paediatric tumours medulloblastoma and ependymoma. https://www.selleckchem.com/products/vx-661.html Our study was performed using the microarray and qPCR techniques and showed PI3K/AKT/mTOR and RAS/MAPK/ERK among the forefront of the list of pathways with the largest number of genes involved in their activation compared to the control. Predicted target analysis indicated the agents from miR-17-92 cluster within miRNAs regulating activity of PI3K/AKT/mTOR and RAS/MAPK/ERK deregulated genes. The expression level of key representatives of the oncogenic cluster, miR-17-5p, and miR-20a, increased with the WHO grade of the analysed cases; the highest levels were found in medulloblastomas.Lipopolysaccharide (LPS) is a potent immunogen when administered locally and/or systemically. The peripheral immunization with LPS could contribute to the progression of neurological diseases because a strong link between neuroinflammation and dopaminergic degeneration has been found. The switch between the survival and neuronal death in substantia nigra could be related to M1 (neurotoxic) and M2 (neuroprotective) microglia phenotypes. In this review, we present the current findings about microglia roles, biomarkers, and natural or synthetic immune modulators determined in the LPS-based murine model.A hypothesis is proposed to explain the pathogenesis of neurodegenerative disease and the diversity of its phenotypes. The hypothesis is based on seven main propositions 1) neurodegenerative disease is associated with multiple risk factors, 2) age is the most important of the risk factors, 3) aging differentially affects neuroanatomical pathways, 4) degeneration of these pathways results in the formation of pathogenic proteins, 5) pathogenic proteins spread along anatomical pathways, 6) the phenotypes of familial and sporadic forms of disease are similar and 7) neurodegenerative disease is characterised by heterogeneity, overlapping phenotypes, and multiple pathology. It is hypothesised that most cases of neurodegenerative disease are multifactorial in which interactions between external environmental and internal genetic risk factors act cumulatively over a lifetime to determine the 'allostatic load' of an individual. The allostatic load determines the rate of neural aging and results in the differential breakdown of neuro-anatomical pathways influenced by their relative use or disuse during life.0 Comments 0 Shares 78 Views 0 Reviews -
These techniques should be applied at specific timing during post-stroke rehabilitation, according to patient's functional status.PURPOSE To assess whether fusion 3D-CTA images can be corrected using non-rigid registration (NRR) for gastroenterology imaging. METHODS This study included 55 patients before gastroenterology surgery who underwent preoperative 3D-CTA prior to gastroenterological surgery. We recorded the coordinate of measurement points on the arterial vessels (X, Y, and Z) in each portal phase, original image of the arterial phase, and arterial phase with NRR. The distance of misregistration between the two points was calculated with the coordinate of the original image with NRR and that of the portal phase as true value. RESULTS The distance of misregistration between the two points in the original arterial and portal phase images was significantly higher than that in the arterial phase image with NRR on all directions (p less then 0.01). CONCLUSIONS This study showed that NRR may correct misregistration on fusion 3D-CTA imaging. Hence, it can visualize correctly the anatomy of the vessel.INTRODUCTION The aim of this paper is to investigate the outcome of patients treated with mastectomy, immediate breast reconstruction (IBR) and post-mastectomy radiotherapy (PMRT) and the risk of late complications. MATERIAL AND METHOD All patients had post-mastectomy, immediate reconstructive surgical procedure by using autologous abdominal implant; tissue expander (TE)/permanent prosthesis (PP); or even combined procedures. Adjuvant external beam radiotherapy treatment (EBRT) was delivered to the reconstructed chest wall and supraclavicular nodes, for a total dose of 50 Gy in 25 fractions. The Kaplan-Meyer analysis evaluates patients' rate of late side effects, Overall Survival (OS), Progression Free survival (PFS), Local-regional free survival (LRFS) and Metastasis Free Survival (MFS). The univariate analysis investigates the correlation between late toxicity and related factors. RESULTS Between November 2003 and October 2016, 91 breast cancer patients were treated with IBR and PMRT. Twenty-three (25.3%) patients experimented late toxicity. Overall, 16 (17.6%) patients experienced late complications which required a surgical approach. The 1- 2- 5- years late toxicity rates were 96.6%, 87.1% and 77.9%, respectively. The type of reconstruction was not statistically related with late toxicity rate (P = 0.35). The median follow-up period was 59 months (range 6-142 months). Median OS was not reached, the 1- 2- 5-years OS rates were 100%, 95.4% and 81% respectively. CONCLUSION This study underlines that the type of reconstruction does not influence late toxicity rate. Moreover, IBR followed by adjuvant radiotherapy, has showed acceptable late toxicity profile and no influence on OS.OBJECTIVES Magnetic resonance imaging (MRI) and computerized tomography (CT) have been widely used to assess palatine tonsils. However, these imaging modalities have some limitations, such as high costs, need for sedation, and exposure to ionizing radiation. Ultrasound has been increasingly used to diagnose tonsillar pathologies. We aim to define normal tonsil size and volume of healthy children according to age. METHODS A total of 274 healthy children were included. Both right and left tonsil sizes were measured in anteroposterior (AP), transverse (Tr.), and longitudinal (Long.) planes. Patients were divided into six subgroups according to their age, and analysis was performed for these subgroups. Age, sex, height, weight, and body mass index were recorded to find possible correlations. RESULTS Median age of the whole population was 7 years (0-16 years). Mean tonsil volume is 1.5 ± 0.9 cm3 for right and left sides. We cannot detect any significant correlation between PT values and sex. We detected a significant positive correlation between PT values and height, weight and BMI. CONCLUSION US can be used as a diagnostic tool for PT pathologies. PT size correlates with age, height, weight, and BMI; however, no correlation is present for sex and side.PURPOSE The purpose of this study was to evaluate the change in capillary blood volume in the muscles of the lower limbs, before and after exercise, using intravoxel incoherent motion (IVIM). MATERIALS AND METHODS Diffusion-weighted images were obtained (with 16 b values) from the thigh and leg muscles of 11 subjects. The imaging was obtained before and immediately exercise; additionally, imaging was performed at 3 h, 6 h, and 24 h after exercise, and an IVIM index was calculated. The exercise involved walking up and down a flight of stairs (140 steps) ten times. The IVIM of each time course-before and after the exercise-was compared. In addition, we examined the correlation of IVIM measurements with the degree of the muscle ache that occurred at 24 h following the exercise. RESULTS The IVIM index significantly increased after exercise compared with that before exercise (P less then 0.01). IVIM decreased at 3 h following exercise, but increased again at 24 h. A correlation was found between the IVIM index at 24 h after exercise and the degree of the muscle ache (r = 0.80) CONCLUSIONS The capillary blood volume significantly increased after exercise when compared to before exercise. The capillary blood volume decreased after exercise at 3 h and 6 h following exercise, but it increased again at 24 h. There was a correlation between the degree of muscle ache and the amount of capillary blood volume measured from the femoral muscle at 24 h after exercise.PURPOSE Salvage radiotherapy is generally considered as the standard treatment for biochemical relapse after surgery. Best results have been obtained with a PSA value less then 0.5 ng/ml at relapse, while 60-66 Gy is deemed as standard total dose. Modern imaging, as dynamic-18F-choline PET/CT may identify site of recurrence, allowing dose escalation to a biological target volume. METHODS Hundred and fifty patients showed a local relapse at dynamic-18F-choline PET/CT at time of biochemical recurrence. High-dose salvage radiotherapy was delivered up to total dose of 80 Gy to 18F-choline PET/CT positive area. Toxicity and relapse-free survival were recorded. https://www.selleckchem.com/products/3-deazaneplanocin-a-dznep.html RESULTS Median PSA value at the beginning of salvage radiotherapy was 0.47 ng/ml (range 0.2-17.5 ng/ml). One-hundred and thirty nine patients (93%) completed salvage radiotherapy without interruptions. Acute gastrointestinal grade ≥ 2 toxicity was recorded in 13 patients (9%), acute genitourinary grade ≥ 2 toxicity in 2 patients (1.4%). One patient (0.7%) experienced late gastrointestinal grade 4 toxicity and 2 patients (1.
These techniques should be applied at specific timing during post-stroke rehabilitation, according to patient's functional status.PURPOSE To assess whether fusion 3D-CTA images can be corrected using non-rigid registration (NRR) for gastroenterology imaging. METHODS This study included 55 patients before gastroenterology surgery who underwent preoperative 3D-CTA prior to gastroenterological surgery. We recorded the coordinate of measurement points on the arterial vessels (X, Y, and Z) in each portal phase, original image of the arterial phase, and arterial phase with NRR. The distance of misregistration between the two points was calculated with the coordinate of the original image with NRR and that of the portal phase as true value. RESULTS The distance of misregistration between the two points in the original arterial and portal phase images was significantly higher than that in the arterial phase image with NRR on all directions (p less then 0.01). CONCLUSIONS This study showed that NRR may correct misregistration on fusion 3D-CTA imaging. Hence, it can visualize correctly the anatomy of the vessel.INTRODUCTION The aim of this paper is to investigate the outcome of patients treated with mastectomy, immediate breast reconstruction (IBR) and post-mastectomy radiotherapy (PMRT) and the risk of late complications. MATERIAL AND METHOD All patients had post-mastectomy, immediate reconstructive surgical procedure by using autologous abdominal implant; tissue expander (TE)/permanent prosthesis (PP); or even combined procedures. Adjuvant external beam radiotherapy treatment (EBRT) was delivered to the reconstructed chest wall and supraclavicular nodes, for a total dose of 50 Gy in 25 fractions. The Kaplan-Meyer analysis evaluates patients' rate of late side effects, Overall Survival (OS), Progression Free survival (PFS), Local-regional free survival (LRFS) and Metastasis Free Survival (MFS). The univariate analysis investigates the correlation between late toxicity and related factors. RESULTS Between November 2003 and October 2016, 91 breast cancer patients were treated with IBR and PMRT. Twenty-three (25.3%) patients experimented late toxicity. Overall, 16 (17.6%) patients experienced late complications which required a surgical approach. The 1- 2- 5- years late toxicity rates were 96.6%, 87.1% and 77.9%, respectively. The type of reconstruction was not statistically related with late toxicity rate (P = 0.35). The median follow-up period was 59 months (range 6-142 months). Median OS was not reached, the 1- 2- 5-years OS rates were 100%, 95.4% and 81% respectively. CONCLUSION This study underlines that the type of reconstruction does not influence late toxicity rate. Moreover, IBR followed by adjuvant radiotherapy, has showed acceptable late toxicity profile and no influence on OS.OBJECTIVES Magnetic resonance imaging (MRI) and computerized tomography (CT) have been widely used to assess palatine tonsils. However, these imaging modalities have some limitations, such as high costs, need for sedation, and exposure to ionizing radiation. Ultrasound has been increasingly used to diagnose tonsillar pathologies. We aim to define normal tonsil size and volume of healthy children according to age. METHODS A total of 274 healthy children were included. Both right and left tonsil sizes were measured in anteroposterior (AP), transverse (Tr.), and longitudinal (Long.) planes. Patients were divided into six subgroups according to their age, and analysis was performed for these subgroups. Age, sex, height, weight, and body mass index were recorded to find possible correlations. RESULTS Median age of the whole population was 7 years (0-16 years). Mean tonsil volume is 1.5 ± 0.9 cm3 for right and left sides. We cannot detect any significant correlation between PT values and sex. We detected a significant positive correlation between PT values and height, weight and BMI. CONCLUSION US can be used as a diagnostic tool for PT pathologies. PT size correlates with age, height, weight, and BMI; however, no correlation is present for sex and side.PURPOSE The purpose of this study was to evaluate the change in capillary blood volume in the muscles of the lower limbs, before and after exercise, using intravoxel incoherent motion (IVIM). MATERIALS AND METHODS Diffusion-weighted images were obtained (with 16 b values) from the thigh and leg muscles of 11 subjects. The imaging was obtained before and immediately exercise; additionally, imaging was performed at 3 h, 6 h, and 24 h after exercise, and an IVIM index was calculated. The exercise involved walking up and down a flight of stairs (140 steps) ten times. The IVIM of each time course-before and after the exercise-was compared. In addition, we examined the correlation of IVIM measurements with the degree of the muscle ache that occurred at 24 h following the exercise. RESULTS The IVIM index significantly increased after exercise compared with that before exercise (P less then 0.01). IVIM decreased at 3 h following exercise, but increased again at 24 h. A correlation was found between the IVIM index at 24 h after exercise and the degree of the muscle ache (r = 0.80) CONCLUSIONS The capillary blood volume significantly increased after exercise when compared to before exercise. The capillary blood volume decreased after exercise at 3 h and 6 h following exercise, but it increased again at 24 h. There was a correlation between the degree of muscle ache and the amount of capillary blood volume measured from the femoral muscle at 24 h after exercise.PURPOSE Salvage radiotherapy is generally considered as the standard treatment for biochemical relapse after surgery. Best results have been obtained with a PSA value less then 0.5 ng/ml at relapse, while 60-66 Gy is deemed as standard total dose. Modern imaging, as dynamic-18F-choline PET/CT may identify site of recurrence, allowing dose escalation to a biological target volume. METHODS Hundred and fifty patients showed a local relapse at dynamic-18F-choline PET/CT at time of biochemical recurrence. High-dose salvage radiotherapy was delivered up to total dose of 80 Gy to 18F-choline PET/CT positive area. Toxicity and relapse-free survival were recorded. https://www.selleckchem.com/products/3-deazaneplanocin-a-dznep.html RESULTS Median PSA value at the beginning of salvage radiotherapy was 0.47 ng/ml (range 0.2-17.5 ng/ml). One-hundred and thirty nine patients (93%) completed salvage radiotherapy without interruptions. Acute gastrointestinal grade ≥ 2 toxicity was recorded in 13 patients (9%), acute genitourinary grade ≥ 2 toxicity in 2 patients (1.4%). One patient (0.7%) experienced late gastrointestinal grade 4 toxicity and 2 patients (1.0 Comments 0 Shares 80 Views 0 Reviews -
6-fold in P35SPfFAD3-1 compared to the 183 content in soybean "Kwangankong". The increased content of 183 in the Pβ-conPfFAD3-1 soybean (T1) resulted in a 52.6% increase in total fatty acids, with a larger decrease in 181 content than 182 content. The increase in 183 content was also maintained and reached 42% in the Pphas PfFAD3-1 transgenic generation T2. Investigations of the agronomic traits of 12 Pβ-conPfFAD3-1 transgenic lines (T1) revealed that plant height, number of branches, nodes, pods, total seeds, and total seed weight were significantly higher in several transgenic lines than those in non-transgenic soybean. Especially, an increase in seed size was observed upon expression of the PfFAD3-1 gene with the β-conglycinin promoter, and 6%-14% higher seed lengths were measured from the transgenic lines. Copyright © 2020 Yeom, Kim, Lee, Cho, Kim, Jung, Oh, Jun, Kim and Chung.Bean common mosaic virus (BCMV), bean common mosaic necrosis virus (BCMNV), and cucumber mosaic virus (CMV) cause serious epidemics in common bean (Phaseolus vulgaris), a vital food security crop in many low-to-medium income countries, particularly in Sub-Saharan Africa. Aphids transmit these viruses "non-persistently," i.e., virions attach loosely to the insects' stylets. Viruses may manipulate aphid-host interactions to enhance transmission. We used direct observation and electrical penetration graph measurements to see if the three viruses induced similar or distinct changes in feeding behaviors of two aphid species, Aphis fabae and Myzus persicae. Both aphids vector BCMV, BCMNV, and CMV but A. fabae is a legume specialist (the dominant species in bean fields) while M. persicae is a generalist that feeds on and transmits viruses to diverse plant hosts. Aphids of both species commenced probing epidermal cells (behavior optimal for virus acquisition and inoculation) sooner on virus-infected plants than on mosmission, and data from this work will be useful in epidemiological modeling of non-persistent vectoring of viruses by aphids. https://www.selleckchem.com/products/Etopophos.html Copyright © 2020 Wamonje, Donnelly, Tungadi, Murphy, Pate, Woodcock, Caulfield, Mutuku, Bruce, Gilligan, Pickett and Carr.Pubescence color of soybean is controlled by two genes, T and Td. In the presence of a dominant T allele, dominant and recessive alleles of the Td locus generate tawny and light tawny (or near-gray) pubescence, respectively. Flavones, responsible for pubescence color, are synthesized via two copies of flavone synthase II genes (FNS II-1 and FNS II-2). This study was conducted to map and clone the Td gene. Genetic and linkage analysis using an F2 population and F3 families derived from a cross between a Clark near-isogenic line with light tawny pubescence (genotype TT tdtd) and a Harosoy near-isogenic line with tawny pubescence (TT TdTd) revealed a single gene for pubescence color around the end of chromosome 3. Genome sequence alignment of plant introductions revealed an association between premature stop codons in Glyma.03G258700 (R2R3 MYB transcription factor) and recessive td allele. Cultivars and lines having near-gray or light tawny pubescence and a gray pubescence cultivar with td allele had premature stop codons in the gene. These results suggest that Glyma.03G258700 corresponds to the Td gene. It was predominantly expressed in pubescence. Compared to a tawny pubescence line, a near-isogenic line with td allele produced extremely small amounts of transcripts of Glyma.03G258700, FNS II-1, and FNS II-2 in pubescence. The promoter of FNS II-1 and FNS II-2 shared cis-acting regulatory elements for binding of MYB proteins. These results suggest that the wild type of Glyma.03G258700 protein may bind to the promoter of FNS II genes and upregulate their expression, resulting in increased flavone content and deeper pubescence color. In contrast, mutated Glyma.03G258700 protein may fail to upregulate the expression of FNS II genes, resulting in decreased flavone content and dilute pubescence color. Copyright © 2020 Yan, Githiri, Liu, Sang, Wang and Takahashi.PIN-FORMED (PIN) auxin efflux carriers with a long central hydrophilic loop (long PINs) have been implicated in organogenesis. However, the role of short hydrophilic loop PINs (short PINs) in organogenesis is largely unknown. In this study, we investigated the role of a short PIN, PIN8, in lateral root (LR) development in Arabidopsis thaliana. The loss-of-function mutation in PIN8 significantly decreased LR density, mostly by affecting the emergence stage. PIN8 showed a sporadic expression pattern along the root vascular cells in the phloem, where the PIN8 protein predominantly localized to intracellular compartments. During LR primordium development, PIN8 was expressed at the late stage. Plasma membrane (PM)-localized long PINs suppressed LR formation when expressed in the PIN8 domain. Conversely, an auxin influx carrier, AUX1, restored the wild-type (WT) LR density when expressed in the PIN8 domain of the pin8 mutant root. Moreover, LR emergence was considerably inhibited when AXR2-1, the dominant negative form of Aux/IAA7, compromised auxin signaling in the PIN8 domain. Consistent with these observations, the expression of many genes implicated in late LR development was suppressed in the pin8 mutant compared with the WT. Our results suggest that the intracellularly localized PIN8 affects LR development most likely by modulating intracellular auxin translocation. Thus, the function of PIN8 is distinctive from that of PM-localized long PINs, where they generate local auxin gradients for organogenesis by conducting cell-to-cell auxin reflux. Copyright © 2020 Lee, Ganguly, Lee, Park and Cho.Plants have evolved mechanisms to improve utilization efficiency or acquisition of inorganic phosphate (Pi) in response to Pi deficiency, such as altering root architecture, secreting acid phosphatases, and activating the expression of genes related to Pi uptake and recycling. Although many genes responsive to Pi starvation have been identified, transcription factors that affect tolerance to Pi deficiency have not been well characterized. We show here that the ectopic expression of B-BOX32 (BBX32) and the mutation of ELONGATED HYPOCOTYL 5 (HY5), whose transcriptional activity is negatively regulated by BBX32, resulted in the tolerance to Pi deficiency in Arabidopsis. The primary root lengths of 35SBBX32 and hy5 plants were only slightly inhibited under Pi deficient condition and the fresh weights were significantly higher than those of wild type. The Pi deficiency-tolerant root phenotype of hy5 was similarly observed when grown on the medium without Pi. In addition, a double mutant, hy5 slr1, without lateral roots, also showed a long primary root phenotype under phosphate deficiency, indicating that the root phenotype of hy5 does not result from an increase of external Pi uptake.
6-fold in P35SPfFAD3-1 compared to the 183 content in soybean "Kwangankong". The increased content of 183 in the Pβ-conPfFAD3-1 soybean (T1) resulted in a 52.6% increase in total fatty acids, with a larger decrease in 181 content than 182 content. The increase in 183 content was also maintained and reached 42% in the Pphas PfFAD3-1 transgenic generation T2. Investigations of the agronomic traits of 12 Pβ-conPfFAD3-1 transgenic lines (T1) revealed that plant height, number of branches, nodes, pods, total seeds, and total seed weight were significantly higher in several transgenic lines than those in non-transgenic soybean. Especially, an increase in seed size was observed upon expression of the PfFAD3-1 gene with the β-conglycinin promoter, and 6%-14% higher seed lengths were measured from the transgenic lines. Copyright © 2020 Yeom, Kim, Lee, Cho, Kim, Jung, Oh, Jun, Kim and Chung.Bean common mosaic virus (BCMV), bean common mosaic necrosis virus (BCMNV), and cucumber mosaic virus (CMV) cause serious epidemics in common bean (Phaseolus vulgaris), a vital food security crop in many low-to-medium income countries, particularly in Sub-Saharan Africa. Aphids transmit these viruses "non-persistently," i.e., virions attach loosely to the insects' stylets. Viruses may manipulate aphid-host interactions to enhance transmission. We used direct observation and electrical penetration graph measurements to see if the three viruses induced similar or distinct changes in feeding behaviors of two aphid species, Aphis fabae and Myzus persicae. Both aphids vector BCMV, BCMNV, and CMV but A. fabae is a legume specialist (the dominant species in bean fields) while M. persicae is a generalist that feeds on and transmits viruses to diverse plant hosts. Aphids of both species commenced probing epidermal cells (behavior optimal for virus acquisition and inoculation) sooner on virus-infected plants than on mosmission, and data from this work will be useful in epidemiological modeling of non-persistent vectoring of viruses by aphids. https://www.selleckchem.com/products/Etopophos.html Copyright © 2020 Wamonje, Donnelly, Tungadi, Murphy, Pate, Woodcock, Caulfield, Mutuku, Bruce, Gilligan, Pickett and Carr.Pubescence color of soybean is controlled by two genes, T and Td. In the presence of a dominant T allele, dominant and recessive alleles of the Td locus generate tawny and light tawny (or near-gray) pubescence, respectively. Flavones, responsible for pubescence color, are synthesized via two copies of flavone synthase II genes (FNS II-1 and FNS II-2). This study was conducted to map and clone the Td gene. Genetic and linkage analysis using an F2 population and F3 families derived from a cross between a Clark near-isogenic line with light tawny pubescence (genotype TT tdtd) and a Harosoy near-isogenic line with tawny pubescence (TT TdTd) revealed a single gene for pubescence color around the end of chromosome 3. Genome sequence alignment of plant introductions revealed an association between premature stop codons in Glyma.03G258700 (R2R3 MYB transcription factor) and recessive td allele. Cultivars and lines having near-gray or light tawny pubescence and a gray pubescence cultivar with td allele had premature stop codons in the gene. These results suggest that Glyma.03G258700 corresponds to the Td gene. It was predominantly expressed in pubescence. Compared to a tawny pubescence line, a near-isogenic line with td allele produced extremely small amounts of transcripts of Glyma.03G258700, FNS II-1, and FNS II-2 in pubescence. The promoter of FNS II-1 and FNS II-2 shared cis-acting regulatory elements for binding of MYB proteins. These results suggest that the wild type of Glyma.03G258700 protein may bind to the promoter of FNS II genes and upregulate their expression, resulting in increased flavone content and deeper pubescence color. In contrast, mutated Glyma.03G258700 protein may fail to upregulate the expression of FNS II genes, resulting in decreased flavone content and dilute pubescence color. Copyright © 2020 Yan, Githiri, Liu, Sang, Wang and Takahashi.PIN-FORMED (PIN) auxin efflux carriers with a long central hydrophilic loop (long PINs) have been implicated in organogenesis. However, the role of short hydrophilic loop PINs (short PINs) in organogenesis is largely unknown. In this study, we investigated the role of a short PIN, PIN8, in lateral root (LR) development in Arabidopsis thaliana. The loss-of-function mutation in PIN8 significantly decreased LR density, mostly by affecting the emergence stage. PIN8 showed a sporadic expression pattern along the root vascular cells in the phloem, where the PIN8 protein predominantly localized to intracellular compartments. During LR primordium development, PIN8 was expressed at the late stage. Plasma membrane (PM)-localized long PINs suppressed LR formation when expressed in the PIN8 domain. Conversely, an auxin influx carrier, AUX1, restored the wild-type (WT) LR density when expressed in the PIN8 domain of the pin8 mutant root. Moreover, LR emergence was considerably inhibited when AXR2-1, the dominant negative form of Aux/IAA7, compromised auxin signaling in the PIN8 domain. Consistent with these observations, the expression of many genes implicated in late LR development was suppressed in the pin8 mutant compared with the WT. Our results suggest that the intracellularly localized PIN8 affects LR development most likely by modulating intracellular auxin translocation. Thus, the function of PIN8 is distinctive from that of PM-localized long PINs, where they generate local auxin gradients for organogenesis by conducting cell-to-cell auxin reflux. Copyright © 2020 Lee, Ganguly, Lee, Park and Cho.Plants have evolved mechanisms to improve utilization efficiency or acquisition of inorganic phosphate (Pi) in response to Pi deficiency, such as altering root architecture, secreting acid phosphatases, and activating the expression of genes related to Pi uptake and recycling. Although many genes responsive to Pi starvation have been identified, transcription factors that affect tolerance to Pi deficiency have not been well characterized. We show here that the ectopic expression of B-BOX32 (BBX32) and the mutation of ELONGATED HYPOCOTYL 5 (HY5), whose transcriptional activity is negatively regulated by BBX32, resulted in the tolerance to Pi deficiency in Arabidopsis. The primary root lengths of 35SBBX32 and hy5 plants were only slightly inhibited under Pi deficient condition and the fresh weights were significantly higher than those of wild type. The Pi deficiency-tolerant root phenotype of hy5 was similarly observed when grown on the medium without Pi. In addition, a double mutant, hy5 slr1, without lateral roots, also showed a long primary root phenotype under phosphate deficiency, indicating that the root phenotype of hy5 does not result from an increase of external Pi uptake.0 Comments 0 Shares 75 Views 0 Reviews -
In this study, we discovered cancer-specific changes in urinary RNAs and metabolites, paving the way for the development of sensitive and specific urinary PCa diagnostic biomarkers either alone or in combination. Our methodology was based on single void urine samples (i.e., without prostatic massage). The integrated analysis of metabolomic and transcriptomic data from these liquid biopsies revealed a glutamate metabolism and tricarboxylic acid cycle node that was specific to prostate-derived cancer cells and cancer-specific metabolic changes in urine.Lipoyl synthases are key enzymes in lipoic acid biosynthesis, a co-factor of several enzyme complexes involved in central metabolism. Plant pyruvate dehydrogenase complex (PDH), located in mitochondria and plastids, catalyses the first step of fatty acid biosynthesis in these organelles. Among their different components, the E2 subunit requires the lipoic acid prosthetic group to be active. De novo lipoic acid biosynthesis is achieved by the successive action of two enzymes on octanoyl-ACP octanoyltransferase (LIP2) and lipoyl synthase (LIP1). In this study, two plastidial lipoyl synthase genes from sunflower (Helianthus annuus L.) were identified (HaLIP1p1 and HaLIP1p2), sequenced and cloned in a heterologous production system (Escherichia coli). Gene expression studies revealed similar expression patterns for both isoforms, with a slight predominance of HaLIP1p1 in vegetative tissues and mature seeds. Tertiary structural models for these enzymes indicate they both have the same theoretical catalytic sites, using lipoyl-lys and 5-deoxyadenosine as docking substrates. The fatty acid profile of E. coli cells overexpressing HaLIP1p1 and HaLIP1p2 did not present major differences, and the in vivo activity of both proteins was confirmed by complementation of an E. coli JW0623 mutant in which lipoyl synthase is defective. Although no significant differences were detected in the total fatty acid composition of transgenic Arabidopsis thaliana seeds overexpressing any of both proteins, a lipidomic analysis revealed a redistribution of the glycerolipid species, accompanied with increased phosphatidylethanolamine (PE) content and a decrease in diacyglycerols (DAG) and phosphatidylcholine (PC). Depletion of the SAM co-factor caused by HaLIP1p1 and HaLIP1p2 overexpression in transgenic plants could explain this remodelling through its effects on PC synthesis.Sphincter-saving surgery (SSS) is the gold standard for rectal cancer surgery but results in a wide spectrum of bowel dysfunction. https://www.selleckchem.com/EGFR(HER).html This study investigated the impact of colonic dysmotility on the incontinent form of bowel dysfunction. Bowel function of patients who received SSS with loop ileostomy for treating rectal cancer was reviewed retrospectively from June 2013 two August 2015 at a single hospital. Immediately after closure of a diverting stoma, patients were tested for the colonic transit time (CTT) using radiopaque markers. Bowel dysfunction at 6 and 12 months after SSS was measured as the severity of fecal incontinence according to the Cleveland Clinic Incontinence Score (CCIS) and the use of an anti-diarrheal drug. A short CTT for the left colonic segment was significantly associated with the high CCIS and use of an antidiarrheal agent at 6 months after sphincter preservation. However, the CTT didn't correlate with the CCIS at 12 months after SSS. Rather, age and surgical method demonstrated a significant association. Colonic dysmotility after SSS appears to intensify fecal incontinence for a relatively short period. Its impact abates within a year.Although APE2 plays essential roles in base excision repair and ATR-Chk1 DNA damage response (DDR) pathways, it remains unknown how the APE2 gene is altered in the human genome and whether APE2 is differentially expressed in cancer patients. Here, we report multiple-cancer analyses of APE2 genomic alterations and mRNA expression from cancer patients using available data from The Cancer Genome Atlas (TCGA). We observe that APE2 genomic alterations occur at ~17% frequency in 14 cancer types (n = 21,769). Most frequent somatic mutations of APE2 appear in uterus (2.89%) and skin (2.47%) tumor samples. Furthermore, APE2 expression is upregulated in tumor tissue compared with matched non-malignant tissue across 5 cancer types including kidney, breast, lung, liver, and uterine cancers, but not in prostate cancer. We also examine the mRNA expression of 13 other DNA repair and DDR genes from matched samples for 6 cancer types. We show that APE2 mRNA expression is positively correlated with PCNA, APE1, XRCC1, PARP1, Chk1, and Chk2 across these 6 tumor tissue types; however, groupings of other DNA repair and DDR genes are correlated with APE2 with different patterns in different cancer types. Taken together, this study demonstrates alterations and abnormal expression of APE2 from multiple cancers.Bats are associated with several important zoonotic viruses from different families. One example includes adeno-associated viruses (AAVs), that are extensively detected in several animals, especially primates. To understand AAVs distribution and genetic diversity in the coastal areas of Southeast China, a total of 415 intestine samples were mostly collected from two provinces of southeast China, i.e., Zhejiang and Fujian province. Intestine samples from five bat species were collected for AAVs detection. The average prevalence rate for AAV detection among these samples was 18.6% (77 positives out of 415 samples) and ranged from 11.8 to 28.9% between the five bat species. This suggests that AAVs are widely distributed in diverse bat populations in southeast coastal areas of China. Based on the genome sequence of bat adeno-associated virus-CXC1(BtAAV-CXC1) from one AAV-positive sample, the genetic diversity of the detected AAVs were assessed and analyzed. Phylogenetic analysis revealed that BtAAV-CXC1 was comparatively distant to other major AAVs from mammals and non-mammals, with only a 52.9~64.7% nucleotide identity. However, they were phylogenetically closer to Rhinolophus sinicus bat adeno-associated virus (Rs-BtAAV1), with a 74.5% nt similarity. Partial analysis of the rep and cap overlapping open reading frame (ORF) sequences from bat AAV samples revealed 48 partial rep sequences and 23 partial cap sequences from positive samples shared 86.9 to 100% and 72.3 to 98.8% nucleotide identities among themselves, respectively. This suggests that the detected AAVs had a distinctly high genetic diversity. These findings led us to conclude that diverse AAVs may be widely distributed in bat populations from the southeast regions of China.
In this study, we discovered cancer-specific changes in urinary RNAs and metabolites, paving the way for the development of sensitive and specific urinary PCa diagnostic biomarkers either alone or in combination. Our methodology was based on single void urine samples (i.e., without prostatic massage). The integrated analysis of metabolomic and transcriptomic data from these liquid biopsies revealed a glutamate metabolism and tricarboxylic acid cycle node that was specific to prostate-derived cancer cells and cancer-specific metabolic changes in urine.Lipoyl synthases are key enzymes in lipoic acid biosynthesis, a co-factor of several enzyme complexes involved in central metabolism. Plant pyruvate dehydrogenase complex (PDH), located in mitochondria and plastids, catalyses the first step of fatty acid biosynthesis in these organelles. Among their different components, the E2 subunit requires the lipoic acid prosthetic group to be active. De novo lipoic acid biosynthesis is achieved by the successive action of two enzymes on octanoyl-ACP octanoyltransferase (LIP2) and lipoyl synthase (LIP1). In this study, two plastidial lipoyl synthase genes from sunflower (Helianthus annuus L.) were identified (HaLIP1p1 and HaLIP1p2), sequenced and cloned in a heterologous production system (Escherichia coli). Gene expression studies revealed similar expression patterns for both isoforms, with a slight predominance of HaLIP1p1 in vegetative tissues and mature seeds. Tertiary structural models for these enzymes indicate they both have the same theoretical catalytic sites, using lipoyl-lys and 5-deoxyadenosine as docking substrates. The fatty acid profile of E. coli cells overexpressing HaLIP1p1 and HaLIP1p2 did not present major differences, and the in vivo activity of both proteins was confirmed by complementation of an E. coli JW0623 mutant in which lipoyl synthase is defective. Although no significant differences were detected in the total fatty acid composition of transgenic Arabidopsis thaliana seeds overexpressing any of both proteins, a lipidomic analysis revealed a redistribution of the glycerolipid species, accompanied with increased phosphatidylethanolamine (PE) content and a decrease in diacyglycerols (DAG) and phosphatidylcholine (PC). Depletion of the SAM co-factor caused by HaLIP1p1 and HaLIP1p2 overexpression in transgenic plants could explain this remodelling through its effects on PC synthesis.Sphincter-saving surgery (SSS) is the gold standard for rectal cancer surgery but results in a wide spectrum of bowel dysfunction. https://www.selleckchem.com/EGFR(HER).html This study investigated the impact of colonic dysmotility on the incontinent form of bowel dysfunction. Bowel function of patients who received SSS with loop ileostomy for treating rectal cancer was reviewed retrospectively from June 2013 two August 2015 at a single hospital. Immediately after closure of a diverting stoma, patients were tested for the colonic transit time (CTT) using radiopaque markers. Bowel dysfunction at 6 and 12 months after SSS was measured as the severity of fecal incontinence according to the Cleveland Clinic Incontinence Score (CCIS) and the use of an anti-diarrheal drug. A short CTT for the left colonic segment was significantly associated with the high CCIS and use of an antidiarrheal agent at 6 months after sphincter preservation. However, the CTT didn't correlate with the CCIS at 12 months after SSS. Rather, age and surgical method demonstrated a significant association. Colonic dysmotility after SSS appears to intensify fecal incontinence for a relatively short period. Its impact abates within a year.Although APE2 plays essential roles in base excision repair and ATR-Chk1 DNA damage response (DDR) pathways, it remains unknown how the APE2 gene is altered in the human genome and whether APE2 is differentially expressed in cancer patients. Here, we report multiple-cancer analyses of APE2 genomic alterations and mRNA expression from cancer patients using available data from The Cancer Genome Atlas (TCGA). We observe that APE2 genomic alterations occur at ~17% frequency in 14 cancer types (n = 21,769). Most frequent somatic mutations of APE2 appear in uterus (2.89%) and skin (2.47%) tumor samples. Furthermore, APE2 expression is upregulated in tumor tissue compared with matched non-malignant tissue across 5 cancer types including kidney, breast, lung, liver, and uterine cancers, but not in prostate cancer. We also examine the mRNA expression of 13 other DNA repair and DDR genes from matched samples for 6 cancer types. We show that APE2 mRNA expression is positively correlated with PCNA, APE1, XRCC1, PARP1, Chk1, and Chk2 across these 6 tumor tissue types; however, groupings of other DNA repair and DDR genes are correlated with APE2 with different patterns in different cancer types. Taken together, this study demonstrates alterations and abnormal expression of APE2 from multiple cancers.Bats are associated with several important zoonotic viruses from different families. One example includes adeno-associated viruses (AAVs), that are extensively detected in several animals, especially primates. To understand AAVs distribution and genetic diversity in the coastal areas of Southeast China, a total of 415 intestine samples were mostly collected from two provinces of southeast China, i.e., Zhejiang and Fujian province. Intestine samples from five bat species were collected for AAVs detection. The average prevalence rate for AAV detection among these samples was 18.6% (77 positives out of 415 samples) and ranged from 11.8 to 28.9% between the five bat species. This suggests that AAVs are widely distributed in diverse bat populations in southeast coastal areas of China. Based on the genome sequence of bat adeno-associated virus-CXC1(BtAAV-CXC1) from one AAV-positive sample, the genetic diversity of the detected AAVs were assessed and analyzed. Phylogenetic analysis revealed that BtAAV-CXC1 was comparatively distant to other major AAVs from mammals and non-mammals, with only a 52.9~64.7% nucleotide identity. However, they were phylogenetically closer to Rhinolophus sinicus bat adeno-associated virus (Rs-BtAAV1), with a 74.5% nt similarity. Partial analysis of the rep and cap overlapping open reading frame (ORF) sequences from bat AAV samples revealed 48 partial rep sequences and 23 partial cap sequences from positive samples shared 86.9 to 100% and 72.3 to 98.8% nucleotide identities among themselves, respectively. This suggests that the detected AAVs had a distinctly high genetic diversity. These findings led us to conclude that diverse AAVs may be widely distributed in bat populations from the southeast regions of China.0 Comments 0 Shares 76 Views 0 Reviews -
CONCLUSIONS Unbiased risk estimates for racial disparities among ABO are now available for stimulating and initiating more complex causal modeling that can lead to understanding how racial health disparities for ABO are mediated and how they can be prevented.BACKGROUND It is estimated that up to a third of patients on opioid agonist therapy (OAT) have attention deficit hyperactivity disorder (ADHD). Treatment by ADHD medication, including a centrally acting stimulant (CAS) or atomoxetine is one of the essential approaches. This study evaluates the use of dispensed ADHD medications in the Norwegian OAT population in the period from 2015 to 2017. Types and doses of ADHD medications, co-dispensations of other potentially addictive drugs like benzodiazepines, z-hypnotics, gabapentinoids, and non-OAT opioids, as well as direct-acting antivirals (DAA) against hepatitis C infection, are investigated. METHODS Information about all dispensed ADHD medication, OAT opioids, and the defined potentially addictive drugs were recorded from the Norwegian Prescription Database. Dispensation rates, the types, and the doses of dispensed ADHD medications were estimated by summarizing the number of dispensations, and the dispensed doses. Logistic regression analyses were employed to aents on OAT in Norway, considering a high prevalence of ADHD in this patient group. On the other hand, concurrent dispensations of multiple addictive drugs were common in this population. Understanding the underlying reasons for such prescribing is essential, and research on how to optimize ADHD medication of patients with ADHD receiving OAT is needed.Following publication of the original article [1], the authors reported an error in Fig. 1f.BACKGROUND Although prophylactic clip application before polypectomy may prevent postpolypectomy bleeding (PPB), the usefulness of prophylactic clipping in the treatment of large pedunculated polyps is controversial in some prospective randomized studies. This study was conducted to evaluate the efficacy of prophylactic clip application and to investigate the predictors of PPB in large pedunculated colorectal polyps. METHODS A total of 137 pedunculated polyps (size ≥1 cm) in 116 patients were prospectively included and randomized into group A (with clipping) and group B (without clipping), and resected. The occurrences of immediate PPB (graded 1-4) and delayed PPB were compared. RESULTS Sixty-seven polyps were allocated in group A and 70 polyps in group B. In both groups, the median polyp diameter was 15 mm (P = 0.173) and the median stalk diameter was 3 mm (P = 0.362). Twenty-eight (20.4%) immediate PPB episodes in 137 polyps occurred, 6 (9.0%) in group A and 22 (31.4%) in group B (P = 0.001). https://www.selleckchem.com/products/jw74.html However, the occurrence of delayed PPB was not different between the groups (P = 0.943). Prophylactic clip application decreased the occurrence of immediate PPB (odds ratio 0.215, 95% confidence interval 0.081-0.571). Moreover, polyp size ≥20 mm and stalk diameter ≥ 4 mm increased the risk of immediate PPB. CONCLUSIONS Clip application before polypectomy of ≥1 cm pedunculated polyps is effective in decreasing the occurrence of immediate PPB. Thus, clip application should be considered before performing snare polypectomy, especially for large polyps with a thick stalk. TRIAL REGISTRATION This research was studied a prospective maneuver and enrolled in a registry of clinical trials run by United States National Library of Medicine at the National Institutes of Health (ClinicalTrials.gov Protocol Registration and Results system ID NCT01437631). This study was registered on September 19, 2011.BACKGROUND The World Health Organization (WHO) recommends household contact investigation for tuberculosis (TB) in high-burden countries. However, household contacts who complete evaluation for TB during contact investigation may have difficulty accessing their test results. Use of automated short-messaging services (SMS) to deliver test results could improve TB status awareness and linkage to care. We sought to explore how household contacts experience test results delivered via SMS, and how these experiences influence follow-up intentions. METHODS We conducted semi-structured interviews with household contacts who participated in a randomized controlled trial evaluating home sputum collection and delivery of TB results via SMS (Pan-African Clinical Trials Registry #201509000877140). We asked about feelings, beliefs, decisions, and behaviors in response to the SMS results. We analyzed the content and emerging themes in relation to the Theory of Planned Behavior. RESULTS We interviewed and achieved thematic saturation with ten household contacts. Nine received TB-negative results and one a TB-positive result. Household contacts reported relief upon receiving SMS confirming their TB status, but also said they lacked confidence in the results delivered by SMS. Some worried that negative results were incorrect until they spoke to a lay health worker (LHW). Household contacts said their long-term intentions to request help or seek care were influenced by perceived consequences of not observing the LHW's instructions related to the SMS and follow-up procedures; beliefs about the curability of TB; anticipated support from LHWs; and perceived barriers to responding to an SMS request for further evaluation. CONCLUSION Household contacts experienced relief when they received results. However, they were less confident about results delivered via SMS than results delivered by LHWs. Delivery of results by SMS should complement continued interaction with LHWs, not replace them.BACKGROUND It is not yet known how antibiotics may affect Serious Bacterial Infections (SBI). Our aim is to describe the presentation, management, and serious bacterial infections (SBI) of febrile children on or off antibiotics. METHODS Retrospective, cohort study of febrile Emergency Department patients, 0-36 months of age, at a single institution, between 2009and 2012. RESULTS Seven hundred fifty-three patients were included 584 in the No-Antibiotics group and 169 (22%) in the Antibiotics group. Age and abnormal lung sounds were predictors for being on antibiotics (OR 2.00 [95% CI 1.23-3.25] and OR 1.04 [95% CI 1.02-1.06] respectively) while female gender, and lower temperatures were negative predictors (OR 0.68 [95%0.47-0.98] and OR 0.47 [95% CI 0.32-0.67] respectively). Antibiotics were prescribed by a physician 89% of the time; the most common one being Amoxicillin/Clavulanic Acid (39%). The antibiotic group got more blood tests (57% vs 45%) and Chest X-Rays (37% vs 25%). Overall, the percent of SBIs (and pneumonias) was statistically the same in both groups (6.
CONCLUSIONS Unbiased risk estimates for racial disparities among ABO are now available for stimulating and initiating more complex causal modeling that can lead to understanding how racial health disparities for ABO are mediated and how they can be prevented.BACKGROUND It is estimated that up to a third of patients on opioid agonist therapy (OAT) have attention deficit hyperactivity disorder (ADHD). Treatment by ADHD medication, including a centrally acting stimulant (CAS) or atomoxetine is one of the essential approaches. This study evaluates the use of dispensed ADHD medications in the Norwegian OAT population in the period from 2015 to 2017. Types and doses of ADHD medications, co-dispensations of other potentially addictive drugs like benzodiazepines, z-hypnotics, gabapentinoids, and non-OAT opioids, as well as direct-acting antivirals (DAA) against hepatitis C infection, are investigated. METHODS Information about all dispensed ADHD medication, OAT opioids, and the defined potentially addictive drugs were recorded from the Norwegian Prescription Database. Dispensation rates, the types, and the doses of dispensed ADHD medications were estimated by summarizing the number of dispensations, and the dispensed doses. Logistic regression analyses were employed to aents on OAT in Norway, considering a high prevalence of ADHD in this patient group. On the other hand, concurrent dispensations of multiple addictive drugs were common in this population. Understanding the underlying reasons for such prescribing is essential, and research on how to optimize ADHD medication of patients with ADHD receiving OAT is needed.Following publication of the original article [1], the authors reported an error in Fig. 1f.BACKGROUND Although prophylactic clip application before polypectomy may prevent postpolypectomy bleeding (PPB), the usefulness of prophylactic clipping in the treatment of large pedunculated polyps is controversial in some prospective randomized studies. This study was conducted to evaluate the efficacy of prophylactic clip application and to investigate the predictors of PPB in large pedunculated colorectal polyps. METHODS A total of 137 pedunculated polyps (size ≥1 cm) in 116 patients were prospectively included and randomized into group A (with clipping) and group B (without clipping), and resected. The occurrences of immediate PPB (graded 1-4) and delayed PPB were compared. RESULTS Sixty-seven polyps were allocated in group A and 70 polyps in group B. In both groups, the median polyp diameter was 15 mm (P = 0.173) and the median stalk diameter was 3 mm (P = 0.362). Twenty-eight (20.4%) immediate PPB episodes in 137 polyps occurred, 6 (9.0%) in group A and 22 (31.4%) in group B (P = 0.001). https://www.selleckchem.com/products/jw74.html However, the occurrence of delayed PPB was not different between the groups (P = 0.943). Prophylactic clip application decreased the occurrence of immediate PPB (odds ratio 0.215, 95% confidence interval 0.081-0.571). Moreover, polyp size ≥20 mm and stalk diameter ≥ 4 mm increased the risk of immediate PPB. CONCLUSIONS Clip application before polypectomy of ≥1 cm pedunculated polyps is effective in decreasing the occurrence of immediate PPB. Thus, clip application should be considered before performing snare polypectomy, especially for large polyps with a thick stalk. TRIAL REGISTRATION This research was studied a prospective maneuver and enrolled in a registry of clinical trials run by United States National Library of Medicine at the National Institutes of Health (ClinicalTrials.gov Protocol Registration and Results system ID NCT01437631). This study was registered on September 19, 2011.BACKGROUND The World Health Organization (WHO) recommends household contact investigation for tuberculosis (TB) in high-burden countries. However, household contacts who complete evaluation for TB during contact investigation may have difficulty accessing their test results. Use of automated short-messaging services (SMS) to deliver test results could improve TB status awareness and linkage to care. We sought to explore how household contacts experience test results delivered via SMS, and how these experiences influence follow-up intentions. METHODS We conducted semi-structured interviews with household contacts who participated in a randomized controlled trial evaluating home sputum collection and delivery of TB results via SMS (Pan-African Clinical Trials Registry #201509000877140). We asked about feelings, beliefs, decisions, and behaviors in response to the SMS results. We analyzed the content and emerging themes in relation to the Theory of Planned Behavior. RESULTS We interviewed and achieved thematic saturation with ten household contacts. Nine received TB-negative results and one a TB-positive result. Household contacts reported relief upon receiving SMS confirming their TB status, but also said they lacked confidence in the results delivered by SMS. Some worried that negative results were incorrect until they spoke to a lay health worker (LHW). Household contacts said their long-term intentions to request help or seek care were influenced by perceived consequences of not observing the LHW's instructions related to the SMS and follow-up procedures; beliefs about the curability of TB; anticipated support from LHWs; and perceived barriers to responding to an SMS request for further evaluation. CONCLUSION Household contacts experienced relief when they received results. However, they were less confident about results delivered via SMS than results delivered by LHWs. Delivery of results by SMS should complement continued interaction with LHWs, not replace them.BACKGROUND It is not yet known how antibiotics may affect Serious Bacterial Infections (SBI). Our aim is to describe the presentation, management, and serious bacterial infections (SBI) of febrile children on or off antibiotics. METHODS Retrospective, cohort study of febrile Emergency Department patients, 0-36 months of age, at a single institution, between 2009and 2012. RESULTS Seven hundred fifty-three patients were included 584 in the No-Antibiotics group and 169 (22%) in the Antibiotics group. Age and abnormal lung sounds were predictors for being on antibiotics (OR 2.00 [95% CI 1.23-3.25] and OR 1.04 [95% CI 1.02-1.06] respectively) while female gender, and lower temperatures were negative predictors (OR 0.68 [95%0.47-0.98] and OR 0.47 [95% CI 0.32-0.67] respectively). Antibiotics were prescribed by a physician 89% of the time; the most common one being Amoxicillin/Clavulanic Acid (39%). The antibiotic group got more blood tests (57% vs 45%) and Chest X-Rays (37% vs 25%). Overall, the percent of SBIs (and pneumonias) was statistically the same in both groups (6.0 Comments 0 Shares 66 Views 0 Reviews -
Thus, there is little empirical support for systematic biases in reports of youth temperament as indexed by psychometric modeling. (PsycInfo Database Record (c) 2020 APA, all rights reserved).Members of high-status groups (e.g., men) often lead social justice efforts that seek to benefit low-status groups (e.g., women), but little is known about how observers respond to such instances of visible and influential solidarity. We presented information about a nonprofit organization seeking to address gender (Study 1, N = 198) or racial (Study 2, N = 216) inequality, in which the leadership team was manipulated to include a numerical majority of either high-status group members or low-status group members. Members of low-status groups who read about the majority high-status leadership team reported lower levels of collective action intentions, compared with those who read about the majority low-status leadership team. Mediation analyses (Studies 1 and 2) and an experimental-causal-chain design (Study 3, N = 405) showed that lower collective action intentions in response to the majority high-status leadership team were mediated by participants' perception of a specific problem presented by high-status group leaders (lower awareness of inequality) and lower levels of hope. Study 4 (N = 555) demonstrated that low-status group members responded more negatively to a majority high-status leadership team in an organization seeking to benefit their low-status ingroup (solidarity context), compared with organizations seeking to benefit other groups (nonsolidarity contexts). Results provide the first evidence that the presence of influential high-status group leaders can discourage members of low-status groups from joining a social justice effort that seeks to benefit their ingroup, and that these negative responses extend beyond preferences predicted by frameworks of ingroup bias and role congruity. (PsycInfo Database Record (c) 2020 APA, all rights reserved).Olfactory impairments, including deficits in odor detection, discrimination, recognition, and changes in odor hedonics, are reported in the early stages of Alzheimer's disease (AD). Rodent models of AD display deficits in odor learning, detection, and discrimination-recapitulating the clinical condition. However, the impact of familial AD genetic mutations on odor hedonics is unknown. We tested 2-, 4-, and 6-month-old 5XFAD (Tg6799) **** in the 5-port odor multiple-choice task designed to assay a variety of odor-guided behaviors, including odor preferences/hedonics. We found that 5XFAD **** investigated odors longer than controls, an effect that was driven by 6-month-old ****. Interestingly, this effect was carried by females in the 5XFAD group, who investigated odors longer than age-matched males. Upon examining behavior directed toward individual odors to test for aberrant odor preferences, we uncovered that 5XFAD females at several ages displayed heightened preferences toward some of the odors, indicating aberrant hedonics. We observed no impairments in the ability to engage in the task in 5XFAD ****. Taken together, 5XFAD ****, particularly 5XFAD females, displayed prolonged odor investigation behavior and enhanced preferences to certain odors. The data provide insight into hedonic alterations that may occur in AD mouse models and how these are influenced by biological sex. (PsycInfo Database Record (c) 2020 APA, all rights reserved).The ability to update predictive relationships and adjust behavior accordingly is critical for survival. Females take longer to update expectancies under conditions of outcome omission. It remains unknown whether that is also the case under conditions when outcomes are delivered such as in overexpectation. Here we examined whether male and female rats are able to learn from overexpectation using the same learning parameters. Our data show that males but not females learn from overexpectation when given just a single day of compound training, whereas both sexes learn when given extended 2 days of overexpectation training. These data provide important insight into sex differences that link with prior work and thus open an avenue for the study of how conflicting memories interact in the male and female brain. (PsycInfo Database Record (c) 2020 APA, all rights reserved).Pavlovian conditioning procedures produce marked individual differences in the form of conditioned behavior. For example, when rats are given conditioning trials in which the temporary insertion of a lever into an operant chamber (the conditioned stimulus, CS) is paired with the delivery of food (the unconditioned stimulus, US), they exhibit knowledge of the lever-food relationship in different ways. For some rats (known as sign-trackers), interactions with the lever dominate, while for others (goal-trackers), approaching the food well dominates. https://www.selleckchem.com/products/alantolactone.html A formal model of Pavlovian conditioning (HeiDI) attributes such individual differences in behavior to variations in the perceived salience of the CS and US. An application of the model in which the perceived salience of the CS declines (i.e., adapts) across its duration predicts changes in these individual differences within the presentation of the CS The sign-tracking bias is predicted to decline and goal-tracking bias is predicted to increase across the presentation of a lever. The accuracy of these predictions was confirmed through analysis of archival data from female and male rats. (PsycInfo Database Record (c) 2020 APA, all rights reserved).The influence of domain knowledge on reading behavior has received limited investigation compared to the influence of, for example, context and/or word frequency. The current study tested participants with and without domain knowledge of the Harry Potter (HP) universe. Fans and non-fans read sentences containing HP, high-frequency (HF), or low-frequency target-words. Targets were presented in contexts that were supportive or unsupportive within a 2 (group fans, non-fans) × 3 (context HP, HF, LF) × 3 (word type HP, HF, LF) mixed design. Thirty-two fans and 22 non-fans read 72 two-sentence experimental items while eye-movement behavior was recorded Initial sentences established context; second sentences contained target-words. Fans processed HP words faster than non-fans. No group difference was observed on HF or LF processing durations, suggesting equivalent reading capabilities. In HP contexts, HP and LF targets were processed equivalently. Processing of HF and LF words was facilitated by their supportive context as expected.
Thus, there is little empirical support for systematic biases in reports of youth temperament as indexed by psychometric modeling. (PsycInfo Database Record (c) 2020 APA, all rights reserved).Members of high-status groups (e.g., men) often lead social justice efforts that seek to benefit low-status groups (e.g., women), but little is known about how observers respond to such instances of visible and influential solidarity. We presented information about a nonprofit organization seeking to address gender (Study 1, N = 198) or racial (Study 2, N = 216) inequality, in which the leadership team was manipulated to include a numerical majority of either high-status group members or low-status group members. Members of low-status groups who read about the majority high-status leadership team reported lower levels of collective action intentions, compared with those who read about the majority low-status leadership team. Mediation analyses (Studies 1 and 2) and an experimental-causal-chain design (Study 3, N = 405) showed that lower collective action intentions in response to the majority high-status leadership team were mediated by participants' perception of a specific problem presented by high-status group leaders (lower awareness of inequality) and lower levels of hope. Study 4 (N = 555) demonstrated that low-status group members responded more negatively to a majority high-status leadership team in an organization seeking to benefit their low-status ingroup (solidarity context), compared with organizations seeking to benefit other groups (nonsolidarity contexts). Results provide the first evidence that the presence of influential high-status group leaders can discourage members of low-status groups from joining a social justice effort that seeks to benefit their ingroup, and that these negative responses extend beyond preferences predicted by frameworks of ingroup bias and role congruity. (PsycInfo Database Record (c) 2020 APA, all rights reserved).Olfactory impairments, including deficits in odor detection, discrimination, recognition, and changes in odor hedonics, are reported in the early stages of Alzheimer's disease (AD). Rodent models of AD display deficits in odor learning, detection, and discrimination-recapitulating the clinical condition. However, the impact of familial AD genetic mutations on odor hedonics is unknown. We tested 2-, 4-, and 6-month-old 5XFAD (Tg6799) mice in the 5-port odor multiple-choice task designed to assay a variety of odor-guided behaviors, including odor preferences/hedonics. We found that 5XFAD mice investigated odors longer than controls, an effect that was driven by 6-month-old mice. Interestingly, this effect was carried by females in the 5XFAD group, who investigated odors longer than age-matched males. Upon examining behavior directed toward individual odors to test for aberrant odor preferences, we uncovered that 5XFAD females at several ages displayed heightened preferences toward some of the odors, indicating aberrant hedonics. We observed no impairments in the ability to engage in the task in 5XFAD mice. Taken together, 5XFAD mice, particularly 5XFAD females, displayed prolonged odor investigation behavior and enhanced preferences to certain odors. The data provide insight into hedonic alterations that may occur in AD mouse models and how these are influenced by biological sex. (PsycInfo Database Record (c) 2020 APA, all rights reserved).The ability to update predictive relationships and adjust behavior accordingly is critical for survival. Females take longer to update expectancies under conditions of outcome omission. It remains unknown whether that is also the case under conditions when outcomes are delivered such as in overexpectation. Here we examined whether male and female rats are able to learn from overexpectation using the same learning parameters. Our data show that males but not females learn from overexpectation when given just a single day of compound training, whereas both sexes learn when given extended 2 days of overexpectation training. These data provide important insight into sex differences that link with prior work and thus open an avenue for the study of how conflicting memories interact in the male and female brain. (PsycInfo Database Record (c) 2020 APA, all rights reserved).Pavlovian conditioning procedures produce marked individual differences in the form of conditioned behavior. For example, when rats are given conditioning trials in which the temporary insertion of a lever into an operant chamber (the conditioned stimulus, CS) is paired with the delivery of food (the unconditioned stimulus, US), they exhibit knowledge of the lever-food relationship in different ways. For some rats (known as sign-trackers), interactions with the lever dominate, while for others (goal-trackers), approaching the food well dominates. https://www.selleckchem.com/products/alantolactone.html A formal model of Pavlovian conditioning (HeiDI) attributes such individual differences in behavior to variations in the perceived salience of the CS and US. An application of the model in which the perceived salience of the CS declines (i.e., adapts) across its duration predicts changes in these individual differences within the presentation of the CS The sign-tracking bias is predicted to decline and goal-tracking bias is predicted to increase across the presentation of a lever. The accuracy of these predictions was confirmed through analysis of archival data from female and male rats. (PsycInfo Database Record (c) 2020 APA, all rights reserved).The influence of domain knowledge on reading behavior has received limited investigation compared to the influence of, for example, context and/or word frequency. The current study tested participants with and without domain knowledge of the Harry Potter (HP) universe. Fans and non-fans read sentences containing HP, high-frequency (HF), or low-frequency target-words. Targets were presented in contexts that were supportive or unsupportive within a 2 (group fans, non-fans) × 3 (context HP, HF, LF) × 3 (word type HP, HF, LF) mixed design. Thirty-two fans and 22 non-fans read 72 two-sentence experimental items while eye-movement behavior was recorded Initial sentences established context; second sentences contained target-words. Fans processed HP words faster than non-fans. No group difference was observed on HF or LF processing durations, suggesting equivalent reading capabilities. In HP contexts, HP and LF targets were processed equivalently. Processing of HF and LF words was facilitated by their supportive context as expected.0 Comments 0 Shares 81 Views 0 Reviews -
The mainstream interventions used during the 2014-2016 Ebola epidemic were contact tracing and case isolation. The Ebola outbreak in Nigeria that formed part of the 2014-2016 epidemic demonstrated the effectiveness of control interventions with a 100% hospitalization rate. Here, we aim to explicitly estimate the protective effect of case isolation, reconstructing the time events of onset of illness and hospitalization as well as the transmission network. We show that case isolation reduced the reproduction number and shortened the serial interval. Employing Bayesian inference with the Markov chain Monte Carlo method for parameter estimation and assuming that the reproduction number exponentially declines over time, the protective effect of case isolation was estimated to be 39.7% (95% credible interval 2.4%-82.1%). The individual protective effect of case isolation was also estimated, showing that the effectiveness was dependent on the speed, i.e. https://www.selleckchem.com/products/FK-506-(Tacrolimus).html the time from onset of illness to hospitalization.We study how the structure of the interaction network affects self-organized collective motion in two minimal models of self-propelled agents the Vicsek model and the Active-Elastic (AE) model. We perform simulations with topologies that interpolate between a nearest-neighbour network and random networks with different degree distributions to analyse the relationship between the interaction topology and the resilience to noise of the ordered state. For the Vicsek case, we find that a higher fraction of random connections with homogeneous or power-law degree distribution increases the critical noise, and thus the resilience to noise, as expected due to small-world effects. Surprisingly, for the AE model, a higher fraction of random links with power-law degree distribution can decrease this resilience, despite most links being long-range. We explain this effect through a simple mechanical analogy, arguing that the larger presence of agents with few connections contributes localized low-energy modes that are easily excited by noise, thus hindering the collective dynamics. These results demonstrate the strong effects of the interaction topology on self-organization. Our work suggests potential roles of the interaction network structure in biological collective behaviour and could also help improve decentralized swarm robotics control and other distributed consensus systems.Intracranial aneurysms frequently develop blood clots, plaque and inflammations, which are linked to enhanced particulate mass deposition. In this work, we propose a computational model for particulate deposition, that accounts for the influence of field forces, such as gravity and electrostatics, which produce an additional flux of particles perpendicular to the fluid motion and towards the wall. This field-mediated flux can significantly enhance particle deposition in low-shear environments, such as in aneurysm cavities. Experimental investigation of particle deposition patterns in in vitro models of side aneurysms, demonstrated the ability of the model to predict enhanced particle adhesion at these sites. Our results showed a significant influence of gravity and electrostatic forces (greater than 10%), indicating that the additional terms presented in our models may be necessary for modelling a wide range of physiological flow conditions and not only for ultra-low shear regions. Spatial differences between the computational model and the experimental results suggested that additional transport and fluidic mechanisms affect the deposition pattern within aneurysms. Taken together, the presented findings may enhance our understanding of pathological deposition processes at cardiovascular disease sites, and facilitate rational design and optimization of cardiovascular particulate drug carriers.
After myocardial infarction, neutrophils rapidly and massively infiltrate the heart, where they promote both tissue healing and damage.
To characterize the dynamics of circulating and cardiac neutrophil diversity after infarction.
We employed single-cell transcriptomics combined with cell surface epitope detection by sequencing to investigate temporal neutrophil diversity in the blood and heart after murine myocardial infarction. At day 1, 3, and 5 after infarction, cardiac Ly6G
(lymphocyte antigen 6G) neutrophils could be delineated into 6 distinct clusters with specific time-dependent patterning and proportions. At day 1, neutrophils were characterized by a gene expression profile proximal to bone marrow neutrophils (
,
,
), and putative activity of transcriptional regulators involved in hypoxic response (
) and emergency granulopoiesis (
). At 3 and 5 days, 2 major subsets of
(enriched for eg,
and
) and
(
) neutrophils were found. Cellular indexing of transcriptomes and epito-cell level, and reveal a process of local tissue specification of neutrophils in the ischemic heart characterized by the acquisition of a SiglecF
signature.
Altogether, our data provide a time-resolved census of neutrophil diversity and gene expression dynamics in the mouse blood and ischemic heart at the single-cell level, and reveal a process of local tissue specification of neutrophils in the ischemic heart characterized by the acquisition of a SiglecFhi signature.Repeating the movements associated with activities such as drawing or sports typically leads to improvements in kinematic behavior these movements become faster, smoother, and exhibit less variation. Likewise, practice has also been shown to lead to faster and smoother movement trajectories in speech articulation. However, little is known about its effect on articulatory variability. To address this, we investigate the extent to which repetition and predictability influence the articulation of the frequent German word "sie" [zi] (they). We find that articulatory variability is proportional to speaking rate and the duration of [zi], and that overall variability decreases as [zi] is repeated during the experiment. Lower variability is also observed as the conditional probability of [zi] increases, and the greatest reduction in variability occurs during the execution of the vocalic target of [i]. These results indicate that practice can produce observable differences in the articulation of even the most common gestures used in speech.
The mainstream interventions used during the 2014-2016 Ebola epidemic were contact tracing and case isolation. The Ebola outbreak in Nigeria that formed part of the 2014-2016 epidemic demonstrated the effectiveness of control interventions with a 100% hospitalization rate. Here, we aim to explicitly estimate the protective effect of case isolation, reconstructing the time events of onset of illness and hospitalization as well as the transmission network. We show that case isolation reduced the reproduction number and shortened the serial interval. Employing Bayesian inference with the Markov chain Monte Carlo method for parameter estimation and assuming that the reproduction number exponentially declines over time, the protective effect of case isolation was estimated to be 39.7% (95% credible interval 2.4%-82.1%). The individual protective effect of case isolation was also estimated, showing that the effectiveness was dependent on the speed, i.e. https://www.selleckchem.com/products/FK-506-(Tacrolimus).html the time from onset of illness to hospitalization.We study how the structure of the interaction network affects self-organized collective motion in two minimal models of self-propelled agents the Vicsek model and the Active-Elastic (AE) model. We perform simulations with topologies that interpolate between a nearest-neighbour network and random networks with different degree distributions to analyse the relationship between the interaction topology and the resilience to noise of the ordered state. For the Vicsek case, we find that a higher fraction of random connections with homogeneous or power-law degree distribution increases the critical noise, and thus the resilience to noise, as expected due to small-world effects. Surprisingly, for the AE model, a higher fraction of random links with power-law degree distribution can decrease this resilience, despite most links being long-range. We explain this effect through a simple mechanical analogy, arguing that the larger presence of agents with few connections contributes localized low-energy modes that are easily excited by noise, thus hindering the collective dynamics. These results demonstrate the strong effects of the interaction topology on self-organization. Our work suggests potential roles of the interaction network structure in biological collective behaviour and could also help improve decentralized swarm robotics control and other distributed consensus systems.Intracranial aneurysms frequently develop blood clots, plaque and inflammations, which are linked to enhanced particulate mass deposition. In this work, we propose a computational model for particulate deposition, that accounts for the influence of field forces, such as gravity and electrostatics, which produce an additional flux of particles perpendicular to the fluid motion and towards the wall. This field-mediated flux can significantly enhance particle deposition in low-shear environments, such as in aneurysm cavities. Experimental investigation of particle deposition patterns in in vitro models of side aneurysms, demonstrated the ability of the model to predict enhanced particle adhesion at these sites. Our results showed a significant influence of gravity and electrostatic forces (greater than 10%), indicating that the additional terms presented in our models may be necessary for modelling a wide range of physiological flow conditions and not only for ultra-low shear regions. Spatial differences between the computational model and the experimental results suggested that additional transport and fluidic mechanisms affect the deposition pattern within aneurysms. Taken together, the presented findings may enhance our understanding of pathological deposition processes at cardiovascular disease sites, and facilitate rational design and optimization of cardiovascular particulate drug carriers. After myocardial infarction, neutrophils rapidly and massively infiltrate the heart, where they promote both tissue healing and damage. To characterize the dynamics of circulating and cardiac neutrophil diversity after infarction. We employed single-cell transcriptomics combined with cell surface epitope detection by sequencing to investigate temporal neutrophil diversity in the blood and heart after murine myocardial infarction. At day 1, 3, and 5 after infarction, cardiac Ly6G (lymphocyte antigen 6G) neutrophils could be delineated into 6 distinct clusters with specific time-dependent patterning and proportions. At day 1, neutrophils were characterized by a gene expression profile proximal to bone marrow neutrophils ( , , ), and putative activity of transcriptional regulators involved in hypoxic response ( ) and emergency granulopoiesis ( ). At 3 and 5 days, 2 major subsets of (enriched for eg, and ) and ( ) neutrophils were found. Cellular indexing of transcriptomes and epito-cell level, and reveal a process of local tissue specification of neutrophils in the ischemic heart characterized by the acquisition of a SiglecF signature. Altogether, our data provide a time-resolved census of neutrophil diversity and gene expression dynamics in the mouse blood and ischemic heart at the single-cell level, and reveal a process of local tissue specification of neutrophils in the ischemic heart characterized by the acquisition of a SiglecFhi signature.Repeating the movements associated with activities such as drawing or sports typically leads to improvements in kinematic behavior these movements become faster, smoother, and exhibit less variation. Likewise, practice has also been shown to lead to faster and smoother movement trajectories in speech articulation. However, little is known about its effect on articulatory variability. To address this, we investigate the extent to which repetition and predictability influence the articulation of the frequent German word "sie" [zi] (they). We find that articulatory variability is proportional to speaking rate and the duration of [zi], and that overall variability decreases as [zi] is repeated during the experiment. Lower variability is also observed as the conditional probability of [zi] increases, and the greatest reduction in variability occurs during the execution of the vocalic target of [i]. These results indicate that practice can produce observable differences in the articulation of even the most common gestures used in speech.0 Comments 0 Shares 2 Views 0 Reviews -
Copyright © 2020 Lee et al.Endochin-like quinolones (ELQs) potently inhibit the proliferation of Plasmodium, Toxoplasma, Neospora, and Babesia by targeting the cytochrome b Qo and Qi sites and interfering with oxidative phosphorylation and pyrimidine biosynthesis. The activities of 14 different ELQs were assessed against B. besnoiti tachyzoites grown in human foreskin fibroblasts (HFF) by quantitative real time PCR. The values for 50% proliferation inhibition (IC50) of five ELQs were determined in a 3-days growth assay after an initial screen of 12 ELQs at 0.01, 0.1, and 1 μM. The IC50s of ELQ-121, -136, and -316 were 0.49, 2.36, and 7.97 nM, respectively. The IC50s of ELQs tested against B. besnoiti were higher than IC50s previously observed for P. falciparum and T. gondii. However, the B. besnoiti cytochrome b sequence and the predicted Qo and Qi ELQ binding sites in the Toxoplasma, Neospora, and Besnoitia cytochrome b are virtually identical, suggesting that the differences in ELQ susceptibility are not due to variations in the substrate binding sites. TEM of ELQ-treated parasites primarily demonstrated alterations within the parasite mitochondrion, profound thickening of the nuclear membrane, as well as increased vacuolization within the tachyzoite cytoplasm. Long-term treatment assays of intracellular B. besnoiti with ELQs for up to 20 days followed by the release of drug pressure caused a substantial delay in parasite growth and proliferation while ELQs were present, but parasite proliferation resumed days after ELQs were removed. Interestingly, structural alterations persisted after ELQ removal and parasite proliferation was slowed. These findings provide a basis for further in vivo studies of ELQs as therapeutic options against B. besnoiti infection. Copyright © 2020 Eberhard, Balmer, Müller, Müller, Winter, Pou, Nilsen, Riscoe, Francisco, Leitao, Doggett and Hemphill.In the present study, the immune-stimulatory effect of two levels of honey bee pollen (5 and 10%, P5 and P10 treatment, respectively) and its supercritical fluid extract (0. 5 and 1%, E0.5 and E1, respectively) included in the diet, was tested in gilthead seabream (Sparus aurata). The in vivo trial was preceded by the evaluation of antioxidant properties of three different bee pollen extracts obtained by water, ethanol 80%, and Supercritic Fluids Extraction (SFE). The preliminary evaluation attested that the SFE showed the lowest extraction yield (10.47%) compared to ethanol 80% (48.61%) and water (45.99%). SFE extract showed good antioxidant properties with high polyphenol content (13.06 mg GAE/g), radical scavenging activity (3.12 mg/ml), reducing power (38.68 mg/mL EC50). On the contrary, the water extract showed the significantly lowest polyphenol content (2 mg GAE/g; P less then 0.05). The results of in vivo trial demonstrate that the diets supplemented with SFE bee pollen extract had a stimulatory effrmulation of fish feeds. Copyright © 2020 Messina, Panettieri, Arena, Renda, Espinosa Ruiz, Morghese, Piccolo, Santulli and Bovera.Listeria ivanovii subsp. ivanovii is an intracellular bacterium distributed widely in nature, causing the listeriosis in ruminants and humans. Previous researches had isolated 116 strains of L. ivanovii subsp. ivanovii from wild rodents and pikas of different regions in China, and the predominant sequence types were ST1 and ST2. In this study, we first investigated the biological characteristics and virulence of these two clonal strains including motility, metabolism and virulence in cells and mouse model. https://www.selleckchem.com/products/eliglustat.html The results demonstrated the ST1 strains exhibited motility, wide metabolic activity and hypervirulence, whereas the ST2 strains showed non-motility, relative lower metabolic activity and virulence. Considering the transmissible ability from wild rodents and pikas to ecological environment, the L. ivanovii subsp. ivanovii with potential pathogenicity to humans and ruminants should be monitored. Copyright © 2020 Gan, Mao, Jiang, Zhang, Liu, Cao, Wang, Wang, Sun, Huang and Ye.Microbiota affects host health and plays an important role in dysbiosis. The study examined the effect of diet including grape seed meal (GSM) with its mixture of bioactive compounds on the large intestine microbiota and short-chain fatty acid synthesis in weaned piglets treated with dextran sodium sulfate (DSS) as a model for inflammatory bowel diseases. Twenty-two piglets were included in four experimental groups based on their diet control, DSS (1 g/kg/b.w.+control diet), GSM (8% grape seed meal inclusion in control diet), and DSS+GSM (1 g/kg/b.w., 8% grape seed meal in control diet). After 30 days, the colon content was isolated and used for microbiota sequencing on an Illumina MiSeq platform. QIIME 1.9.1 pipeline was used to process the raw sequences. Both GSM and DSS alone and in combination affected the diversity indices and FirmicutesBacteroidetes ratio, with significantly higher values in the DSS-afflicted piglets for Proteobacteria phylum, Roseburia, Megasphera and CF231 genus, and lower values for Lactobacillus. GSM with high-fiber, polyphenol and polyunsaturated fatty acid (PUFA) content increased the production of butyrate and isobutyrate, stimulated the growth of beneficial genera like Prevotella and Megasphaera, while countering the relative abundance of Roseburia, reducing it to half of the DSS value and contributing to the management of the DSS effects. Copyright © 2020 Grosu, Pistol, Marin, Cişmileanu, Palade and Ţăranu.It has long been observed in clinical practice that a subset of patients with Lyme disease report a constellation of symptoms such as fatigue, cognitive difficulties, and musculoskeletal pain, which may last for a significant period of time. These symptoms, which can range from mild to severe, have been reported throughout the literature in both prospective and population-based studies in Lyme disease endemic regions. The etiology of these symptoms is unknown, however several illness-causing mechanisms have been hypothesized, including microbial persistence, host immune dysregulation through inflammatory or secondary autoimmune pathways, or altered neural networks, as in central sensitization. Evaluation and characterization of persistent symptoms in Lyme disease is complicated by potential independent, repeat exposures to B. burgdorferi, as well as the potential for co-morbid diseases with overlapping symptom profiles. Antibody testing for B. burgdorferi is an insensitive measure after treatment, and no other FDA-approved tests currently exist.
Copyright © 2020 Lee et al.Endochin-like quinolones (ELQs) potently inhibit the proliferation of Plasmodium, Toxoplasma, Neospora, and Babesia by targeting the cytochrome b Qo and Qi sites and interfering with oxidative phosphorylation and pyrimidine biosynthesis. The activities of 14 different ELQs were assessed against B. besnoiti tachyzoites grown in human foreskin fibroblasts (HFF) by quantitative real time PCR. The values for 50% proliferation inhibition (IC50) of five ELQs were determined in a 3-days growth assay after an initial screen of 12 ELQs at 0.01, 0.1, and 1 μM. The IC50s of ELQ-121, -136, and -316 were 0.49, 2.36, and 7.97 nM, respectively. The IC50s of ELQs tested against B. besnoiti were higher than IC50s previously observed for P. falciparum and T. gondii. However, the B. besnoiti cytochrome b sequence and the predicted Qo and Qi ELQ binding sites in the Toxoplasma, Neospora, and Besnoitia cytochrome b are virtually identical, suggesting that the differences in ELQ susceptibility are not due to variations in the substrate binding sites. TEM of ELQ-treated parasites primarily demonstrated alterations within the parasite mitochondrion, profound thickening of the nuclear membrane, as well as increased vacuolization within the tachyzoite cytoplasm. Long-term treatment assays of intracellular B. besnoiti with ELQs for up to 20 days followed by the release of drug pressure caused a substantial delay in parasite growth and proliferation while ELQs were present, but parasite proliferation resumed days after ELQs were removed. Interestingly, structural alterations persisted after ELQ removal and parasite proliferation was slowed. These findings provide a basis for further in vivo studies of ELQs as therapeutic options against B. besnoiti infection. Copyright © 2020 Eberhard, Balmer, Müller, Müller, Winter, Pou, Nilsen, Riscoe, Francisco, Leitao, Doggett and Hemphill.In the present study, the immune-stimulatory effect of two levels of honey bee pollen (5 and 10%, P5 and P10 treatment, respectively) and its supercritical fluid extract (0. 5 and 1%, E0.5 and E1, respectively) included in the diet, was tested in gilthead seabream (Sparus aurata). The in vivo trial was preceded by the evaluation of antioxidant properties of three different bee pollen extracts obtained by water, ethanol 80%, and Supercritic Fluids Extraction (SFE). The preliminary evaluation attested that the SFE showed the lowest extraction yield (10.47%) compared to ethanol 80% (48.61%) and water (45.99%). SFE extract showed good antioxidant properties with high polyphenol content (13.06 mg GAE/g), radical scavenging activity (3.12 mg/ml), reducing power (38.68 mg/mL EC50). On the contrary, the water extract showed the significantly lowest polyphenol content (2 mg GAE/g; P less then 0.05). The results of in vivo trial demonstrate that the diets supplemented with SFE bee pollen extract had a stimulatory effrmulation of fish feeds. Copyright © 2020 Messina, Panettieri, Arena, Renda, Espinosa Ruiz, Morghese, Piccolo, Santulli and Bovera.Listeria ivanovii subsp. ivanovii is an intracellular bacterium distributed widely in nature, causing the listeriosis in ruminants and humans. Previous researches had isolated 116 strains of L. ivanovii subsp. ivanovii from wild rodents and pikas of different regions in China, and the predominant sequence types were ST1 and ST2. In this study, we first investigated the biological characteristics and virulence of these two clonal strains including motility, metabolism and virulence in cells and mouse model. https://www.selleckchem.com/products/eliglustat.html The results demonstrated the ST1 strains exhibited motility, wide metabolic activity and hypervirulence, whereas the ST2 strains showed non-motility, relative lower metabolic activity and virulence. Considering the transmissible ability from wild rodents and pikas to ecological environment, the L. ivanovii subsp. ivanovii with potential pathogenicity to humans and ruminants should be monitored. Copyright © 2020 Gan, Mao, Jiang, Zhang, Liu, Cao, Wang, Wang, Sun, Huang and Ye.Microbiota affects host health and plays an important role in dysbiosis. The study examined the effect of diet including grape seed meal (GSM) with its mixture of bioactive compounds on the large intestine microbiota and short-chain fatty acid synthesis in weaned piglets treated with dextran sodium sulfate (DSS) as a model for inflammatory bowel diseases. Twenty-two piglets were included in four experimental groups based on their diet control, DSS (1 g/kg/b.w.+control diet), GSM (8% grape seed meal inclusion in control diet), and DSS+GSM (1 g/kg/b.w., 8% grape seed meal in control diet). After 30 days, the colon content was isolated and used for microbiota sequencing on an Illumina MiSeq platform. QIIME 1.9.1 pipeline was used to process the raw sequences. Both GSM and DSS alone and in combination affected the diversity indices and FirmicutesBacteroidetes ratio, with significantly higher values in the DSS-afflicted piglets for Proteobacteria phylum, Roseburia, Megasphera and CF231 genus, and lower values for Lactobacillus. GSM with high-fiber, polyphenol and polyunsaturated fatty acid (PUFA) content increased the production of butyrate and isobutyrate, stimulated the growth of beneficial genera like Prevotella and Megasphaera, while countering the relative abundance of Roseburia, reducing it to half of the DSS value and contributing to the management of the DSS effects. Copyright © 2020 Grosu, Pistol, Marin, Cişmileanu, Palade and Ţăranu.It has long been observed in clinical practice that a subset of patients with Lyme disease report a constellation of symptoms such as fatigue, cognitive difficulties, and musculoskeletal pain, which may last for a significant period of time. These symptoms, which can range from mild to severe, have been reported throughout the literature in both prospective and population-based studies in Lyme disease endemic regions. The etiology of these symptoms is unknown, however several illness-causing mechanisms have been hypothesized, including microbial persistence, host immune dysregulation through inflammatory or secondary autoimmune pathways, or altered neural networks, as in central sensitization. Evaluation and characterization of persistent symptoms in Lyme disease is complicated by potential independent, repeat exposures to B. burgdorferi, as well as the potential for co-morbid diseases with overlapping symptom profiles. Antibody testing for B. burgdorferi is an insensitive measure after treatment, and no other FDA-approved tests currently exist.0 Comments 0 Shares 72 Views 0 Reviews -
OBJECTIVE We aimed to identify the prognostic factors in head and neck squamous cell carcinoma (HNSCC) by using gene expression analysis and candidate biomarkers for adjuvant therapy. STUDY DESIGN Complementary DNA (cDNA) microarray analysis was performed by using samples from 8 patients, who had died as a result of fulminant recurrence shortly after postoperative radiation therapy, and the results were compared with those from patients with HNSCC of similar stage, but without recurrence. Tissue microarray and immunohistochemistry of samples from 69 patients with oral cavity squamous cell carcinoma indicated ErbB3 to be a prognostic marker, and its expression was analyzed in the HNSCC cell lines. Sapitinib was tested as a concurrent inhibitor of EGFR, ErbB2, and ErbB3. In 15 ****, tumor xenograft was implanted at the lateral tongue, and tumor growth was evaluated. RESULTS ErbB3 overexpression in patients with treatment-resistant HNSCC was associated with relapse-free survival, disease-free survival, and overall survival (P = .018, P = .006, and P = .003, respectively). In the HNSCC cell line, ErbB2 and ErbB3 overexpression was inhibited by postoperative adjuvant therapy with sapitinib, which was also seen to improve survival in an animal model. CONCLUSIONS ErbB3 overexpression predicts a poor clinical outcome. Sapitinib was shown to be an effective inhibitor in the HNSCC cell line and animal models of cancer but with no statistical significance. Further studies with larger groups are needed to better support these results. BACKGROUND Supporting women to continue breastfeeding is a global challenge. The Milky Way Program is an effective face to face intervention to increase breastfeeding rates up to six months postpartum. The sustainability and access to the Milky Way Program could be enhanced by transforming it into a mobile application allowing women to access relevant information from their own place at a convenient time. AIM To explore the process of transforming the Milky Way Program into an acceptable and usable mobile health application. METHOD Stakeholders including multidisciplinary researchers and end-users designed the application based on the Milky Way Program by using Persuasive System Design principles. A mixed-method approach was used in the development and evaluation process. Seven women were recruited through convenience sampling to pilot test the application. The women's feedback was collected through an online survey six weeks after birth and individual interviews at four months postpartum. FINDINGS Women in the pilot study reported that the breastfeeding application was well designed, easy to use, interactive, reassuring and evidence-based with credible sources of information. CONCLUSION The Persuasive System Design model combined with end-user engagement can feasibly inform the development of an acceptable and usable mobile health application for breastfeeding based on a proven clinical intervention. Further rigorous testing is required to evaluate the effectiveness of the application on breastfeeding initiation and duration. OBJECTIVE We determine how aggregate costs have changed for commonly used emergency department (ED) medications, and assess drivers of cost increases. METHODS Using the National Hospital Ambulatory Medical Care Survey (NHAMCS), we identified the top 150 ED medications administered and prescribed at discharge in 2015. We used average wholesale prices (AWP) for each year from 2006 to 15 from the Red Book (Truven Health Analytics Inc.). Average wholesale price per patient (AWPP) was calculated by dividing AWP by drug uses. This was then multiplied by the total drug administrations or prescriptions to estimate the total cost in a given the year. All prices were converted to 2015 dollars. RESULTS Aggregate costs of drugs administered in the ED increased from $688.7 million in 2006 to $882.4 million in 2015. For discharge prescriptions, aggregate costs increased from $2.031 billion in 2006 to $4.572 billion in 2015. AWPP for drugs administered in the ED in 2015 was 14.5% higher than in 2006 and 24.3% higher at discharge. The largest absolute increase in AWPP for drugs administered was for glucagon, which increased from $111 in 2006 to $235 in 2015. The largest AWPP increase at discharge was for epinephrine auto-injector, which increased from $124 in 2006 and to $481 in 2015. CONCLUSION Over the course of the study period, the aggregate costs of the most common medications administered in the ED increased by 28% while the costs of medications prescribed at discharge increased 125%. BACKGROUND Emergency department-initiated buprenorphine (EDIB) programs have been shown to improve treatment outcomes for patients with opioid use disorders (OUD); however, little is known about how EDIB implementation impacts the patient census at participating hospitals. OBJECTIVES To determine if implementation of an EDIB program was associated with changes in the number of patients presenting to the ED seeking treatment for substance use disorder (SUD). METHODS We conducted a retrospective evaluation at a single academic ED that began offering EDIB in December 2017. Data span the period of December 2016 to April 2019, All ED visits with a chief complaint of addiction problem, detoxification, drug/alcohol assessment, drug problem, or withdrawal charted by nursing at the time of triage were eligible for inclusion. Charts were reviewed to determine (1) treatment status and (2) substance(s) for which the patient was seeking treatment. An interrupted time series analysis was used to compare the pre- and post-EDIB rates for all-substance, as well as opioid-specific, treatment-seeking visits. RESULTS For all-substance visits, the predicted level change in the treatment-seeking rate after EDIB was implemented was positive but not significant (0.000497, p = 0.53); the trend change after EDIB was also not significant (-0.00004, p = 0.73). For visits involving opioids, the predicted level change was (0.000638, p = 0.21); and the trend change was (0.000047, p = 0.49). https://www.selleckchem.com/products/p22077.html CONCLUSION Implementation of an EDIB program was not associated with increased rates of presentation by patients requesting treatment for a substance use disorder in the participating ED setting.
OBJECTIVE We aimed to identify the prognostic factors in head and neck squamous cell carcinoma (HNSCC) by using gene expression analysis and candidate biomarkers for adjuvant therapy. STUDY DESIGN Complementary DNA (cDNA) microarray analysis was performed by using samples from 8 patients, who had died as a result of fulminant recurrence shortly after postoperative radiation therapy, and the results were compared with those from patients with HNSCC of similar stage, but without recurrence. Tissue microarray and immunohistochemistry of samples from 69 patients with oral cavity squamous cell carcinoma indicated ErbB3 to be a prognostic marker, and its expression was analyzed in the HNSCC cell lines. Sapitinib was tested as a concurrent inhibitor of EGFR, ErbB2, and ErbB3. In 15 mice, tumor xenograft was implanted at the lateral tongue, and tumor growth was evaluated. RESULTS ErbB3 overexpression in patients with treatment-resistant HNSCC was associated with relapse-free survival, disease-free survival, and overall survival (P = .018, P = .006, and P = .003, respectively). In the HNSCC cell line, ErbB2 and ErbB3 overexpression was inhibited by postoperative adjuvant therapy with sapitinib, which was also seen to improve survival in an animal model. CONCLUSIONS ErbB3 overexpression predicts a poor clinical outcome. Sapitinib was shown to be an effective inhibitor in the HNSCC cell line and animal models of cancer but with no statistical significance. Further studies with larger groups are needed to better support these results. BACKGROUND Supporting women to continue breastfeeding is a global challenge. The Milky Way Program is an effective face to face intervention to increase breastfeeding rates up to six months postpartum. The sustainability and access to the Milky Way Program could be enhanced by transforming it into a mobile application allowing women to access relevant information from their own place at a convenient time. AIM To explore the process of transforming the Milky Way Program into an acceptable and usable mobile health application. METHOD Stakeholders including multidisciplinary researchers and end-users designed the application based on the Milky Way Program by using Persuasive System Design principles. A mixed-method approach was used in the development and evaluation process. Seven women were recruited through convenience sampling to pilot test the application. The women's feedback was collected through an online survey six weeks after birth and individual interviews at four months postpartum. FINDINGS Women in the pilot study reported that the breastfeeding application was well designed, easy to use, interactive, reassuring and evidence-based with credible sources of information. CONCLUSION The Persuasive System Design model combined with end-user engagement can feasibly inform the development of an acceptable and usable mobile health application for breastfeeding based on a proven clinical intervention. Further rigorous testing is required to evaluate the effectiveness of the application on breastfeeding initiation and duration. OBJECTIVE We determine how aggregate costs have changed for commonly used emergency department (ED) medications, and assess drivers of cost increases. METHODS Using the National Hospital Ambulatory Medical Care Survey (NHAMCS), we identified the top 150 ED medications administered and prescribed at discharge in 2015. We used average wholesale prices (AWP) for each year from 2006 to 15 from the Red Book (Truven Health Analytics Inc.). Average wholesale price per patient (AWPP) was calculated by dividing AWP by drug uses. This was then multiplied by the total drug administrations or prescriptions to estimate the total cost in a given the year. All prices were converted to 2015 dollars. RESULTS Aggregate costs of drugs administered in the ED increased from $688.7 million in 2006 to $882.4 million in 2015. For discharge prescriptions, aggregate costs increased from $2.031 billion in 2006 to $4.572 billion in 2015. AWPP for drugs administered in the ED in 2015 was 14.5% higher than in 2006 and 24.3% higher at discharge. The largest absolute increase in AWPP for drugs administered was for glucagon, which increased from $111 in 2006 to $235 in 2015. The largest AWPP increase at discharge was for epinephrine auto-injector, which increased from $124 in 2006 and to $481 in 2015. CONCLUSION Over the course of the study period, the aggregate costs of the most common medications administered in the ED increased by 28% while the costs of medications prescribed at discharge increased 125%. BACKGROUND Emergency department-initiated buprenorphine (EDIB) programs have been shown to improve treatment outcomes for patients with opioid use disorders (OUD); however, little is known about how EDIB implementation impacts the patient census at participating hospitals. OBJECTIVES To determine if implementation of an EDIB program was associated with changes in the number of patients presenting to the ED seeking treatment for substance use disorder (SUD). METHODS We conducted a retrospective evaluation at a single academic ED that began offering EDIB in December 2017. Data span the period of December 2016 to April 2019, All ED visits with a chief complaint of addiction problem, detoxification, drug/alcohol assessment, drug problem, or withdrawal charted by nursing at the time of triage were eligible for inclusion. Charts were reviewed to determine (1) treatment status and (2) substance(s) for which the patient was seeking treatment. An interrupted time series analysis was used to compare the pre- and post-EDIB rates for all-substance, as well as opioid-specific, treatment-seeking visits. RESULTS For all-substance visits, the predicted level change in the treatment-seeking rate after EDIB was implemented was positive but not significant (0.000497, p = 0.53); the trend change after EDIB was also not significant (-0.00004, p = 0.73). For visits involving opioids, the predicted level change was (0.000638, p = 0.21); and the trend change was (0.000047, p = 0.49). https://www.selleckchem.com/products/p22077.html CONCLUSION Implementation of an EDIB program was not associated with increased rates of presentation by patients requesting treatment for a substance use disorder in the participating ED setting.0 Comments 0 Shares 2 Views 0 Reviews
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