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  • Plant disease resistance is largely governed by complex genetic architecture. In maize, few disease resistance loci have been characterized. Near-isogenic lines are a powerful genetic tool to dissect quantitative trait loci. We analyzed an introgression library of maize (Zea mays) near-isogenic lines, termed a nested near-isogenic line library for resistance to northern leaf blight caused by the fungal pathogen Setosphaeria turcica The population was comprised of 412 BC5F4 near-isogenic lines that originated from 18 diverse donor parents and a common recurrent parent, B73. Single nucleotide polymorphisms identified through genotyping by sequencing were used to define introgressions and for association analysis. Near-isogenic lines that conferred resistance and susceptibility to northern leaf blight were comprised of introgressions that overlapped known northern leaf blight quantitative trait loci. Genome-wide association analysis and stepwise regression further resolved five quantitative trait loci regions, and implicated several candidate genes, including Liguleless1, a key determinant of leaf architecture in cereals. Two independently-derived mutant alleles of liguleless1 inoculated with S. turcica showed enhanced susceptibility to northern leaf blight. In the maize nested association mapping population, leaf angle was positively correlated with resistance to northern leaf blight in five recombinant inbred line populations, and negatively correlated with northern leaf blight in four recombinant inbred line populations. https://www.selleckchem.com/products/ly2780301.html This study demonstrates the power of an introgression library combined with high density marker coverage to resolve quantitative trait loci. Furthermore, the role of liguleless1 in leaf architecture and in resistance to northern leaf blight has important applications in crop improvement.Husk has multiple functions such as protecting ears from diseases, infection, and dehydration during development. Additionally, husks comprised of fewer, shorter, thinner, and narrower layers allow faster moisture evaporation of kernels prior to harvest. Intensive studies have been conducted to identify appropriate husk architecture by understanding the genetic basis of related traits, including husk length, husk layer number, husk thickness, and husk width. However, marker-assisted selection is inefficient because the identified quantitative trait loci and associated genetic loci could only explain a small proportion of total phenotypic variation. Genomic selection (GS) has been used successfully on many species including maize on other traits. Thus, the potential of using GS for husk traits to directly identify superior inbred lines, without knowing the specific underlying genetic loci, is well worth exploring. In this study, we compared four GS models on a maize association population with 498 inbred lines belonging to four subpopulations, including 27 lines in stiff stalk, 67 lines in non-stiff stalk, 193 lines in tropical-subtropical, and 211 lines in mixture subpopulations. Genomic Best Linear Unbiased Prediction with principal components as cofactor, performed the best and was selected to examine the impact of interaction between sampling proportions and subpopulations. We found that predictions on inbred lines in a subpopulation were benefited from excluding individuals from other subpopulations for training if the training population within the subpopulation was large enough. Husk thickness exhibited the highest prediction accuracy among all husk traits. These results gave strategic insight to improve husk architecture.The developing central nervous system (CNS) is particularly prone to malignant transformation, but the underlying mechanisms remain unresolved. However, periods of tumor susceptibility appear to correlate with windows of increased proliferation, which are often observed during embryonic and fetal stages and reflect stereotypical changes in the proliferative properties of neural progenitors. The temporal mechanisms underlying these proliferation patterns are still unclear in mammals. In Drosophila, two decades of work have revealed a network of sequentially expressed transcription factors and RNA-binding proteins that compose a neural progenitor-intrinsic temporal patterning system. Temporal patterning controls both the identity of the post-mitotic progeny of neural progenitors, according to the order in which they arose, and the proliferative properties of neural progenitors along development. In addition, in Drosophila, temporal patterning delineates early windows of cancer susceptibility and is aberrantly regulated in developmental tumors to govern cellular hierarchy as well as the metabolic and proliferative heterogeneity of tumor cells. Whereas recent studies have shown that similar genetic programs unfold during both fetal development and pediatric brain tumors, I discuss, in this Review, how the concept of temporal patterning that was pioneered in Drosophila could help to understand the mechanisms of initiation and progression of CNS tumors in children.Breast cancers are divided into subtypes with different prognoses and treatment responses based on global differences in gene expression. Luminal breast cancer gene expression and proliferation are driven by estrogen receptor alpha, and targeting this transcription factor is the most effective therapy for this subtype. By contrast, it remains unclear which transcription factors drive the gene expression signature that defines basal-like triple-negative breast cancer, and there are no targeted therapies approved to treat this aggressive subtype. In this study, we utilized integrated genomic analysis of DNA methylation, chromatin accessibility, transcription factor binding, and gene expression in large collections of breast cancer cell lines and patient tumors to identify transcription factors responsible for the basal-like gene expression program. Glucocorticoid receptor (GR) and STAT3 bind to the same genomic regulatory regions, which were specifically open and unmethylated in basal-like breast cancer. These transcription factors cooperated to regulate expression of hundreds of genes in the basal-like gene expression signature, which were associated with poor prognosis. Combination treatment with small-molecule inhibitors of both transcription factors resulted in synergistic decreases in cell growth in cell lines and patient-derived organoid models. This study demonstrates that GR and STAT3 cooperate to regulate the basal-like breast cancer gene expression program and provides the basis for improved therapy for basal-like triple-negative breast cancer through rational combination of STAT3 and GR inhibitors. SIGNIFICANCE This study demonstrates that GR and STAT3 cooperate to activate the canonical gene expression signature of basal-like triple-negative breast cancer and that combination treatment with STAT3 and GR inhibitors could provide synergistic therapeutic efficacy.
    Plant disease resistance is largely governed by complex genetic architecture. In maize, few disease resistance loci have been characterized. Near-isogenic lines are a powerful genetic tool to dissect quantitative trait loci. We analyzed an introgression library of maize (Zea mays) near-isogenic lines, termed a nested near-isogenic line library for resistance to northern leaf blight caused by the fungal pathogen Setosphaeria turcica The population was comprised of 412 BC5F4 near-isogenic lines that originated from 18 diverse donor parents and a common recurrent parent, B73. Single nucleotide polymorphisms identified through genotyping by sequencing were used to define introgressions and for association analysis. Near-isogenic lines that conferred resistance and susceptibility to northern leaf blight were comprised of introgressions that overlapped known northern leaf blight quantitative trait loci. Genome-wide association analysis and stepwise regression further resolved five quantitative trait loci regions, and implicated several candidate genes, including Liguleless1, a key determinant of leaf architecture in cereals. Two independently-derived mutant alleles of liguleless1 inoculated with S. turcica showed enhanced susceptibility to northern leaf blight. In the maize nested association mapping population, leaf angle was positively correlated with resistance to northern leaf blight in five recombinant inbred line populations, and negatively correlated with northern leaf blight in four recombinant inbred line populations. https://www.selleckchem.com/products/ly2780301.html This study demonstrates the power of an introgression library combined with high density marker coverage to resolve quantitative trait loci. Furthermore, the role of liguleless1 in leaf architecture and in resistance to northern leaf blight has important applications in crop improvement.Husk has multiple functions such as protecting ears from diseases, infection, and dehydration during development. Additionally, husks comprised of fewer, shorter, thinner, and narrower layers allow faster moisture evaporation of kernels prior to harvest. Intensive studies have been conducted to identify appropriate husk architecture by understanding the genetic basis of related traits, including husk length, husk layer number, husk thickness, and husk width. However, marker-assisted selection is inefficient because the identified quantitative trait loci and associated genetic loci could only explain a small proportion of total phenotypic variation. Genomic selection (GS) has been used successfully on many species including maize on other traits. Thus, the potential of using GS for husk traits to directly identify superior inbred lines, without knowing the specific underlying genetic loci, is well worth exploring. In this study, we compared four GS models on a maize association population with 498 inbred lines belonging to four subpopulations, including 27 lines in stiff stalk, 67 lines in non-stiff stalk, 193 lines in tropical-subtropical, and 211 lines in mixture subpopulations. Genomic Best Linear Unbiased Prediction with principal components as cofactor, performed the best and was selected to examine the impact of interaction between sampling proportions and subpopulations. We found that predictions on inbred lines in a subpopulation were benefited from excluding individuals from other subpopulations for training if the training population within the subpopulation was large enough. Husk thickness exhibited the highest prediction accuracy among all husk traits. These results gave strategic insight to improve husk architecture.The developing central nervous system (CNS) is particularly prone to malignant transformation, but the underlying mechanisms remain unresolved. However, periods of tumor susceptibility appear to correlate with windows of increased proliferation, which are often observed during embryonic and fetal stages and reflect stereotypical changes in the proliferative properties of neural progenitors. The temporal mechanisms underlying these proliferation patterns are still unclear in mammals. In Drosophila, two decades of work have revealed a network of sequentially expressed transcription factors and RNA-binding proteins that compose a neural progenitor-intrinsic temporal patterning system. Temporal patterning controls both the identity of the post-mitotic progeny of neural progenitors, according to the order in which they arose, and the proliferative properties of neural progenitors along development. In addition, in Drosophila, temporal patterning delineates early windows of cancer susceptibility and is aberrantly regulated in developmental tumors to govern cellular hierarchy as well as the metabolic and proliferative heterogeneity of tumor cells. Whereas recent studies have shown that similar genetic programs unfold during both fetal development and pediatric brain tumors, I discuss, in this Review, how the concept of temporal patterning that was pioneered in Drosophila could help to understand the mechanisms of initiation and progression of CNS tumors in children.Breast cancers are divided into subtypes with different prognoses and treatment responses based on global differences in gene expression. Luminal breast cancer gene expression and proliferation are driven by estrogen receptor alpha, and targeting this transcription factor is the most effective therapy for this subtype. By contrast, it remains unclear which transcription factors drive the gene expression signature that defines basal-like triple-negative breast cancer, and there are no targeted therapies approved to treat this aggressive subtype. In this study, we utilized integrated genomic analysis of DNA methylation, chromatin accessibility, transcription factor binding, and gene expression in large collections of breast cancer cell lines and patient tumors to identify transcription factors responsible for the basal-like gene expression program. Glucocorticoid receptor (GR) and STAT3 bind to the same genomic regulatory regions, which were specifically open and unmethylated in basal-like breast cancer. These transcription factors cooperated to regulate expression of hundreds of genes in the basal-like gene expression signature, which were associated with poor prognosis. Combination treatment with small-molecule inhibitors of both transcription factors resulted in synergistic decreases in cell growth in cell lines and patient-derived organoid models. This study demonstrates that GR and STAT3 cooperate to regulate the basal-like breast cancer gene expression program and provides the basis for improved therapy for basal-like triple-negative breast cancer through rational combination of STAT3 and GR inhibitors. SIGNIFICANCE This study demonstrates that GR and STAT3 cooperate to activate the canonical gene expression signature of basal-like triple-negative breast cancer and that combination treatment with STAT3 and GR inhibitors could provide synergistic therapeutic efficacy.
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  • Peste des petits ruminants virus (PPRV) causes an infectious disease of high morbidity and mortality among sheep and goats which impacts millions of livestock keepers globally. PPRV transmission risk varies by production system, but a deeper understanding of how transmission scales in these systems and which husbandry practices impact risk is needed. To investigate transmission scaling and husbandry practice-associated risk, this study combined 395 household questionnaires with over 7115 cross-sectional serosurvey samples collected in Tanzania among agropastoral and pastoral households managing sheep, goats, or cattle (most managed all three, n = 284, 71.9%). Although self-reported compound-level herd size was significantly larger in pastoral than agropastoral households, the data show no evidence that household herd force of infection (FOI, per capita infection rate of susceptible hosts) increased with herd size. Seroprevalence and FOI patterns observed at the sub-village level showed significant spatial variation in FOI. Univariate analyses showed that household herd FOI was significantly higher when households reported seasonal grazing camp attendance, cattle or goat introduction to the compound, death, ****, or giving away of animals in the past 12 months, when cattle were grazed separately from sheep and goats, and when the household also managed dogs or donkeys. Multivariable analyses revealed that species, production system type, and goat or sheep introduction or seasonal grazing camp attendance, cattle or goat death or sales, or goats given away in the past 12 months significantly increased odds of seroconversion, whereas managing pigs or cattle attending seasonal grazing camps had significantly lower odds of seroconversion. Further research should investigate specific husbandry practices across production systems in other countries and in systems that include additional atypical host species to broaden understanding of PPRV transmission.Addressing the psychological mechanisms and structural inequalities that underpin mental health issues is critical to recovery following disasters and pandemics. The Asia Pacific Disaster Mental Health Network was established in June 2020 in response to the current disaster climate and to foster advancements in disaster-oriented mental health research, practice and policy across the region. Supported by the World Health Organization (WHO) Thematic Platform for Health Emergency and Disaster Risk Management (Health EDRM), the network brings together leading disaster psychiatry, psychology and public health experts. Our aim is to advance policy, research and targeted translation of the evidence so that communities are better informed in preparation and response to disasters, pandemics and mass trauma. https://www.selleckchem.com/products/amlexanox.html The first meetings of the network resulted in the development of a regional disaster mental health agenda focused on the current context, with five priority areas (1) Strengthening community engagement and the integration of diverse perspectives in planning, implementing and evaluating mental health and psychosocial response in disasters; (2) Supporting and assessing the capacity of mental health systems to respond to disasters; (3) Optimising emerging technologies in mental healthcare; (4) Understanding and responding appropriately to addressing the mental health impacts of climate change; (5) Prioritising mental health and psychosocial support for high-risk groups. Consideration of these priority areas in future research, practice and policy will support nuanced and effective psychosocial initiatives for disaster-affected populations within the Asia Pacific region.Grounded in achievement goal theory and self-determination theory, this study aimed to examine the associations of students' perception of learning- and performance-oriented climates created by teachers and peers on basic psychological needs satisfaction, and consequently their relationships with physical education grades. This study had a cross-sectional design, and 589 students aged between 10 and 18 years (M = 12.93; SD = 1.49) were recruited for analysis. Participants completed a multisection survey assessing motivational climates and basic psychological needs, and physical education grades were provided by the physical education teacher. Students' perception of learning-oriented climates created by teachers and peers was positively and significantly associated with basic psychological needs satisfaction. Additionally, these learning-oriented climates presented a significant indirect association with physical education grades. On the other hand, the performance-oriented climate created by teachers had a negative and significant relationship with basic psychological needs satisfaction and displayed a negative indirect relationship with physical education grades. The performance-oriented climate created by peers had a positive and significant relationship with basic psychological needs satisfaction and displayed a positive indirect relationship with physical education grades. The perception of performance-oriented climates created by peers could represent a boost within the students in physical education features. Teachers have the responsibility of promoting task and learning environments in which students experience positive outcomes, not only on a motivational level but also on a cognitive level.Chocolate vine (Akebia quinata) is consumed as a fruit and is also used in traditional medicine. In order to identify the bioactive components of A. quinata, a phytosterol glucoside stigmasterol-3-O-β-d-glucoside (1), three triterpenoids maslinic acid (2), scutellaric acid (3), and hederagenin (4), and three triterpenoidal saponins akebia saponin PA (5), hederacoside C (6), and hederacolchiside F (7) were isolated from a 70% EtOH extract of the fruits of A. quinata (AKQU). The chemical structures of isolates 1-7 were determined by analyzing the 1D and 2D nuclear magnetic resonance (NMR) spectroscopic data. Here, we evaluated the effects of AKQU and compounds 1-7 on insulin secretion using the INS-1 rat pancreatic β-cell line. Glucose-stimulated insulin secretion (GSIS) was evaluated in INS-1 cells using the GSIS assay. The expression levels of the proteins related to pancreatic β-cell function were detected by Western blotting. Among the isolates, stigmasterol-3-O-β-d-glucoside (1) exhibited strong GSIS activity and triggered the overexpression of pancreas/duodenum homeobox protein-1 (PDX-1), which is implicated in the regulation of pancreatic β-cell survival and function.
    Peste des petits ruminants virus (PPRV) causes an infectious disease of high morbidity and mortality among sheep and goats which impacts millions of livestock keepers globally. PPRV transmission risk varies by production system, but a deeper understanding of how transmission scales in these systems and which husbandry practices impact risk is needed. To investigate transmission scaling and husbandry practice-associated risk, this study combined 395 household questionnaires with over 7115 cross-sectional serosurvey samples collected in Tanzania among agropastoral and pastoral households managing sheep, goats, or cattle (most managed all three, n = 284, 71.9%). Although self-reported compound-level herd size was significantly larger in pastoral than agropastoral households, the data show no evidence that household herd force of infection (FOI, per capita infection rate of susceptible hosts) increased with herd size. Seroprevalence and FOI patterns observed at the sub-village level showed significant spatial variation in FOI. Univariate analyses showed that household herd FOI was significantly higher when households reported seasonal grazing camp attendance, cattle or goat introduction to the compound, death, sale, or giving away of animals in the past 12 months, when cattle were grazed separately from sheep and goats, and when the household also managed dogs or donkeys. Multivariable analyses revealed that species, production system type, and goat or sheep introduction or seasonal grazing camp attendance, cattle or goat death or sales, or goats given away in the past 12 months significantly increased odds of seroconversion, whereas managing pigs or cattle attending seasonal grazing camps had significantly lower odds of seroconversion. Further research should investigate specific husbandry practices across production systems in other countries and in systems that include additional atypical host species to broaden understanding of PPRV transmission.Addressing the psychological mechanisms and structural inequalities that underpin mental health issues is critical to recovery following disasters and pandemics. The Asia Pacific Disaster Mental Health Network was established in June 2020 in response to the current disaster climate and to foster advancements in disaster-oriented mental health research, practice and policy across the region. Supported by the World Health Organization (WHO) Thematic Platform for Health Emergency and Disaster Risk Management (Health EDRM), the network brings together leading disaster psychiatry, psychology and public health experts. Our aim is to advance policy, research and targeted translation of the evidence so that communities are better informed in preparation and response to disasters, pandemics and mass trauma. https://www.selleckchem.com/products/amlexanox.html The first meetings of the network resulted in the development of a regional disaster mental health agenda focused on the current context, with five priority areas (1) Strengthening community engagement and the integration of diverse perspectives in planning, implementing and evaluating mental health and psychosocial response in disasters; (2) Supporting and assessing the capacity of mental health systems to respond to disasters; (3) Optimising emerging technologies in mental healthcare; (4) Understanding and responding appropriately to addressing the mental health impacts of climate change; (5) Prioritising mental health and psychosocial support for high-risk groups. Consideration of these priority areas in future research, practice and policy will support nuanced and effective psychosocial initiatives for disaster-affected populations within the Asia Pacific region.Grounded in achievement goal theory and self-determination theory, this study aimed to examine the associations of students' perception of learning- and performance-oriented climates created by teachers and peers on basic psychological needs satisfaction, and consequently their relationships with physical education grades. This study had a cross-sectional design, and 589 students aged between 10 and 18 years (M = 12.93; SD = 1.49) were recruited for analysis. Participants completed a multisection survey assessing motivational climates and basic psychological needs, and physical education grades were provided by the physical education teacher. Students' perception of learning-oriented climates created by teachers and peers was positively and significantly associated with basic psychological needs satisfaction. Additionally, these learning-oriented climates presented a significant indirect association with physical education grades. On the other hand, the performance-oriented climate created by teachers had a negative and significant relationship with basic psychological needs satisfaction and displayed a negative indirect relationship with physical education grades. The performance-oriented climate created by peers had a positive and significant relationship with basic psychological needs satisfaction and displayed a positive indirect relationship with physical education grades. The perception of performance-oriented climates created by peers could represent a boost within the students in physical education features. Teachers have the responsibility of promoting task and learning environments in which students experience positive outcomes, not only on a motivational level but also on a cognitive level.Chocolate vine (Akebia quinata) is consumed as a fruit and is also used in traditional medicine. In order to identify the bioactive components of A. quinata, a phytosterol glucoside stigmasterol-3-O-β-d-glucoside (1), three triterpenoids maslinic acid (2), scutellaric acid (3), and hederagenin (4), and three triterpenoidal saponins akebia saponin PA (5), hederacoside C (6), and hederacolchiside F (7) were isolated from a 70% EtOH extract of the fruits of A. quinata (AKQU). The chemical structures of isolates 1-7 were determined by analyzing the 1D and 2D nuclear magnetic resonance (NMR) spectroscopic data. Here, we evaluated the effects of AKQU and compounds 1-7 on insulin secretion using the INS-1 rat pancreatic β-cell line. Glucose-stimulated insulin secretion (GSIS) was evaluated in INS-1 cells using the GSIS assay. The expression levels of the proteins related to pancreatic β-cell function were detected by Western blotting. Among the isolates, stigmasterol-3-O-β-d-glucoside (1) exhibited strong GSIS activity and triggered the overexpression of pancreas/duodenum homeobox protein-1 (PDX-1), which is implicated in the regulation of pancreatic β-cell survival and function.
    0 Commentaires 0 Parts 297 Vue 0 Aperçu

  • Our objective was to define, describe and organize (on the basis of consensus) the patient's preferences in the management of ulcerative colitis (UC), in order to further incorporate them in daily practice and improve patients satisfaction, adherence to the treatment and quality of care.

    Qualitative study. A narrative literature review in Medline using Mesh and free-text terms was conducted to identify articles on UC patient preferences as well as clinical scenarios that may influence the preferences. The results were presented and discussed in a multidisciplinary nominal group meeting composed of six gastroenterologists, one primary care physician, one nurse practitioner and one expert patient. Key clinical scenarios and patient preferences were then defined, generating a series of points to consider and recommendations. The level of agreement with the final selection of preferences was established following a Delphi process.

    The narrative review retrieved 69 articles of qualitative design and moderate quality. The following key clinical scenarios were identified diagnosis, follow-up, surgery, and special situations/patients profiles such as adolescents or women. Patient preferences were classified into information, treatment (pharmacological and non-pharmacological), follow-up, relations with health professionals, relations with the health system and administration. Finally, 11 recommendations on patient preferences for UC in relation to its management reached the level of agreement established.

    The consensual description of patient's preferences contribute to identify different areas for improvement in healthcare practice.
    The consensual description of patient's preferences contribute to identify different areas for improvement in healthcare practice.
    Bismuth has antimicrobial activity and can improve the efficacy of triple Helicobacter pylori (H. pylori) therapy. Allicin added to conventional therapy for H. pylori infection also improves H. pylori eradication rates. Thus, this study aims to evaluate and compare the efficacy, safety and tolerability of allicin-containing quadruple therapy and bismuth-containing quadruple therapy and to investigate the factors that affect the eradication rates.

    Two hundred twenty H. pylori-infected patients were included and randomly (11) assigned to 14-day quadruple therapy ilaprazole (5 mg bid), doxycycline (100 mg bid), and furazolidone (100 mg bid) with an allicin soft capsule (40 mg of DATS tid) (IDFA) or colloidal bismuth tartrate (220 mg of elemental bismuth bid) (IDFB). Eradication was confirmed by urea breath tests. Symptom improvement, adverse events, and adherence were assessed by a questionnaire.

    In the intention-to-treat and per-protocol analysis, the eradication rates for IDFA and IDFB groups were 87.5% (70/80) vs. 86.3% (69/80, P = 0.815) and 91.9% (68/74) vs. 91.8% (67/73, P = 0.980) as first-line therapies; 83.3% (25/30) vs. 83.3% (25/30, P = 1) and 89.3% (25/28) vs. 88.9% (24/27, P = 1) as second-line therapies. Symptom improvement rates were 96.1% and 97.0% for IDFA and IDFB (P = 1). The adverse event rates were 10.9% in IDFA and 14.5% in IDFB groups (P = 0.418). Nausea occurred frequently in IDFB than IDFA (1.8% vs. 8.2%, P = 0.030). Smoking and sharing utensils significantly affected the efficacy.

    Allicin-containing quadruple therapy might be regarded as a promising alternative to bismuth-containing quadruple therapy in H. pylori eradication.
    Allicin-containing quadruple therapy might be regarded as a promising alternative to bismuth-containing quadruple therapy in H. pylori eradication.Cannabinoids, cannabis, and cannabis-based medicines (CBMs) are increasingly used to manage pain, with limited understanding of their efficacy and safety. We summarised efficacy and adverse events (AEs) of these types of drugs for treating pain using randomised controlled trials in people of any age, with any type of pain, and for any treatment duration. Primary outcomes were 30% and 50% reduction in pain intensity, and AEs. We assessed risk of bias of included studies, and the overall quality of evidence using GRADE. Studies of 7 days (risk difference 0.06, 95% confidence interval 0.01-0.12; 6 trials, 1484 patients, very low-quality evidence). No other beneficial effects were found for other types of cannabinoids, cannabis, or CBM in our primary analyses; 81% of subgroup analyses were negative. Cannabis, nabiximols, and delta-9-tetrahydrocannabinol had more AEs than control. Studies in this field have unclear or high risk of bias, and outcomes had GRADE rating of low- or very low-quality evidence. We have little confidence in the estimates of effect. The evidence neither supports nor refutes claims of efficacy and safety for cannabinoids, cannabis, or CBM in the management of pain.Cannabinoids, cannabis, and cannabis-based medicines (CBM) are increasingly used to manage pain, with limited understanding of their efficacy and safety. We assessed methodological quality, scope, and results of systematic reviews of randomised controlled trials of these treatments. Several search strategies sought self-declared systematic reviews. Methodological quality was assessed using both AMSTAR-2 and techniques important for bias reduction in pain studies. Of the 106 articles read, 57 were self-declared systematic reviews, most published since 2010. https://www.selleckchem.com/products/sgi-110.html They included any type of cannabinoid, cannabis, or CBM, at any dose, however administered, in a broad range of pain conditions. No review examined the effects of a particular cannabinoid, at a particular dose, using a particular route of administration, for a particular pain condition, reporting a particular analgesic outcome. Confidence in the results in the systematic reviews using AMSTAR-2 definitions was critically low (41), low (8), moderate (6), or high (2). Few used criteria important for bias reduction in pain. Cochrane reviews typically provided higher confidence; all industry-conflicted reviews provided critically low confidence. Meta-analyses typically pooled widely disparate studies, and, where assessable, were subject to potential publication bias. Systematic reviews with positive or negative recommendation for use of cannabinoids, cannabis, or CBM in pain typically rated critically low or low (24/25 [96%] positive; 10/12 [83%] negative). Current reviews are mostly lacking in quality and cannot provide a basis for decision-making. A new high-quality systematic review of randomised controlled trials is needed to critically assess the clinical evidence for cannabinoids, cannabis, or CBM in pain.
    Our objective was to define, describe and organize (on the basis of consensus) the patient's preferences in the management of ulcerative colitis (UC), in order to further incorporate them in daily practice and improve patients satisfaction, adherence to the treatment and quality of care. Qualitative study. A narrative literature review in Medline using Mesh and free-text terms was conducted to identify articles on UC patient preferences as well as clinical scenarios that may influence the preferences. The results were presented and discussed in a multidisciplinary nominal group meeting composed of six gastroenterologists, one primary care physician, one nurse practitioner and one expert patient. Key clinical scenarios and patient preferences were then defined, generating a series of points to consider and recommendations. The level of agreement with the final selection of preferences was established following a Delphi process. The narrative review retrieved 69 articles of qualitative design and moderate quality. The following key clinical scenarios were identified diagnosis, follow-up, surgery, and special situations/patients profiles such as adolescents or women. Patient preferences were classified into information, treatment (pharmacological and non-pharmacological), follow-up, relations with health professionals, relations with the health system and administration. Finally, 11 recommendations on patient preferences for UC in relation to its management reached the level of agreement established. The consensual description of patient's preferences contribute to identify different areas for improvement in healthcare practice. The consensual description of patient's preferences contribute to identify different areas for improvement in healthcare practice. Bismuth has antimicrobial activity and can improve the efficacy of triple Helicobacter pylori (H. pylori) therapy. Allicin added to conventional therapy for H. pylori infection also improves H. pylori eradication rates. Thus, this study aims to evaluate and compare the efficacy, safety and tolerability of allicin-containing quadruple therapy and bismuth-containing quadruple therapy and to investigate the factors that affect the eradication rates. Two hundred twenty H. pylori-infected patients were included and randomly (11) assigned to 14-day quadruple therapy ilaprazole (5 mg bid), doxycycline (100 mg bid), and furazolidone (100 mg bid) with an allicin soft capsule (40 mg of DATS tid) (IDFA) or colloidal bismuth tartrate (220 mg of elemental bismuth bid) (IDFB). Eradication was confirmed by urea breath tests. Symptom improvement, adverse events, and adherence were assessed by a questionnaire. In the intention-to-treat and per-protocol analysis, the eradication rates for IDFA and IDFB groups were 87.5% (70/80) vs. 86.3% (69/80, P = 0.815) and 91.9% (68/74) vs. 91.8% (67/73, P = 0.980) as first-line therapies; 83.3% (25/30) vs. 83.3% (25/30, P = 1) and 89.3% (25/28) vs. 88.9% (24/27, P = 1) as second-line therapies. Symptom improvement rates were 96.1% and 97.0% for IDFA and IDFB (P = 1). The adverse event rates were 10.9% in IDFA and 14.5% in IDFB groups (P = 0.418). Nausea occurred frequently in IDFB than IDFA (1.8% vs. 8.2%, P = 0.030). Smoking and sharing utensils significantly affected the efficacy. Allicin-containing quadruple therapy might be regarded as a promising alternative to bismuth-containing quadruple therapy in H. pylori eradication. Allicin-containing quadruple therapy might be regarded as a promising alternative to bismuth-containing quadruple therapy in H. pylori eradication.Cannabinoids, cannabis, and cannabis-based medicines (CBMs) are increasingly used to manage pain, with limited understanding of their efficacy and safety. We summarised efficacy and adverse events (AEs) of these types of drugs for treating pain using randomised controlled trials in people of any age, with any type of pain, and for any treatment duration. Primary outcomes were 30% and 50% reduction in pain intensity, and AEs. We assessed risk of bias of included studies, and the overall quality of evidence using GRADE. Studies of 7 days (risk difference 0.06, 95% confidence interval 0.01-0.12; 6 trials, 1484 patients, very low-quality evidence). No other beneficial effects were found for other types of cannabinoids, cannabis, or CBM in our primary analyses; 81% of subgroup analyses were negative. Cannabis, nabiximols, and delta-9-tetrahydrocannabinol had more AEs than control. Studies in this field have unclear or high risk of bias, and outcomes had GRADE rating of low- or very low-quality evidence. We have little confidence in the estimates of effect. The evidence neither supports nor refutes claims of efficacy and safety for cannabinoids, cannabis, or CBM in the management of pain.Cannabinoids, cannabis, and cannabis-based medicines (CBM) are increasingly used to manage pain, with limited understanding of their efficacy and safety. We assessed methodological quality, scope, and results of systematic reviews of randomised controlled trials of these treatments. Several search strategies sought self-declared systematic reviews. Methodological quality was assessed using both AMSTAR-2 and techniques important for bias reduction in pain studies. Of the 106 articles read, 57 were self-declared systematic reviews, most published since 2010. https://www.selleckchem.com/products/sgi-110.html They included any type of cannabinoid, cannabis, or CBM, at any dose, however administered, in a broad range of pain conditions. No review examined the effects of a particular cannabinoid, at a particular dose, using a particular route of administration, for a particular pain condition, reporting a particular analgesic outcome. Confidence in the results in the systematic reviews using AMSTAR-2 definitions was critically low (41), low (8), moderate (6), or high (2). Few used criteria important for bias reduction in pain. Cochrane reviews typically provided higher confidence; all industry-conflicted reviews provided critically low confidence. Meta-analyses typically pooled widely disparate studies, and, where assessable, were subject to potential publication bias. Systematic reviews with positive or negative recommendation for use of cannabinoids, cannabis, or CBM in pain typically rated critically low or low (24/25 [96%] positive; 10/12 [83%] negative). Current reviews are mostly lacking in quality and cannot provide a basis for decision-making. A new high-quality systematic review of randomised controlled trials is needed to critically assess the clinical evidence for cannabinoids, cannabis, or CBM in pain.
    0 Commentaires 0 Parts 102 Vue 0 Aperçu

  • Moreover, overexpression of bHLH6 in an spx4 background did not affect the Pi content of spx4 under high- and low-P conditions. The bhlh6 spx4 double mutant showed lower shoot Pi concentrations and transcript levels of OsPT3 and OsPT10 compared with the spx4 mutant under high-P conditions. RNA sequencing results indicated that bHLH6 overexpression and spx4 mutant lines share many differentially expressed Pi-responsive genes. Therefore, bHLH6 is an important regulator for Pi signaling and homeostasis which antagonizes SPX4. This knowledge helps elucidate the molecular regulation of plant adaptation to Pi deficiency and will promote efforts toward the creation of low Pi-tolerant crops.Rab-interacting lysosomal protein (RILP) has been suggested to perform as a tumor suppressor in breast and prostate cancer cell lines. However, its expression profile and functional role in lung cancer have never been investigated. We applied the well-established cancer genomic database-The Cancer Genome Atlas to compare the RILP expression and methylation between lung cancer tissues and normal tissues. The potential correlation of RILP with clinical characteristics of lung cancer patients (e.g., stages, smoking, TP53, and methylation) was also be explored. Our results showed that the downregulation of RILP and upregulation of RILP methylation were identified in lung cancer tissues compared to normal healthy tissues. Downregulation of RILP was positively associated with lung cancer later stage (N3), smoking history, TP53 mutation, and poor prognosis, as well as inversely correlated with DNA (cytosine-5)-methyltransferase 1 (DNMT1) expression. Demethylation treatment enhanced RILP expression in lung cancer cells, suggesting hypermethylation is responsible for RILP silencing in lung cancer. https://www.selleckchem.com/products/ly2780301.html We further found that RILP depletion promoted lung cancer cell proliferation, migration, and invasion. We concluded that RILP acts as a tumor suppressor in lung cancer cells. Our results provided the theoretical basis for developing RILP-targeting or demethylating agents for lung cancer treatment.XynII is a family 11 glycoside hydrolase that uses the retaining mechanism for catalysis. In the active site, E177 works as the acid/base and E86 works as the nucleophile. Mutating an uncharged residue (N44) to an acidic residue (D) near E177 decreases the enzyme's optimal pH by ~ 1.0 unit. D44 was previously suggested to be a second proton carrier for catalysis. To test this hypothesis, we abolished the activity of E177 by mutating it to be Q, and mutated N44 to be D or E. These double mutants have dramatically decreased activities. Our high-resolution crystallographic structures and the microscopic pKa calculations show that D44 has similar position and pKa value during catalysis, indicating that D44 changes electrostatics around E177, which makes it prone to rotate as the acid/base in acidic conditions, thus decreases the pH optimum. Our results could be helpful to design enzymes with different pH optimum.Aminoacyl-tRNA synthetase-interacting multifunctional protein 2 (AIMP2) is a non-enzymatic component required for the multi-tRNA synthetase complex. While exon 2 skipping alternatively spliced variant of AIMP2 (AIMP2-DX2) compromises AIMP2 activity and is associated with carcinogenesis, its clinical potential awaits further validation. Here, we found that AIMP2-DX2/AIMP2 expression ratio is strongly correlated with major cancer signaling pathways and poor prognosis, particularly in acute myeloid leukemia (AML). Analysis of a clinical patient cohort revealed that AIMP2-DX2 positive AML patients show decreased overall survival and progression-free survival. We also developed targeted RNA-sequencing and single-molecule RNA-FISH tools to quantitatively analyze AIMP2-DX2/AIMP2 ratios at the single-cell level. By subclassifying hematologic cancer cells based on their AIMP2-DX2/AIMP2 ratios, we found that downregulating AIMP2-DX2 sensitizes cells to anticancer drugs only for a subgroup of cells while it has adverse effects on others. Collectively, our study establishes AIMP2-DX2 as a potential biomarker and a therapeutic target for hematologic cancer.The logical AND gate gene circuit based on the CRISPR-Cas9 system can distinguish bladder cancer cells from normal bladder epithelial cells. However, the layered artificial gene circuits have the problems of high complexity, difficulty in accurately predicting the behavior, and excessive redundancy, which cannot be applied to clinical translation. Here, we construct minigene circuits based on the CRISPReader, a technology used to control promoter-less gene expression in a robust manner. The minigene circuits significantly induce robust gene expression output in bladder cancer cells, but have nearly undetectable gene expression in normal bladder epithelial cells. The minigene circuits show a higher capability for cancer identification and intervention when compared with traditional gene circuits, and could be used for in vivo cancer gene therapy using the all-in-one AAV vector. This approach expands the design ideas and concepts of gene circuits in medical synthetic biology.Helicoverpa armigera is a major insect pest of several crops worldwide. This insect is susceptible to some Bacillus thuringiensis (Bt) Cry insecticidal proteins expressed in transgenic crops or used in biopesticides. Previously, we identified H. armigera prohibitin (PHB) as a Cry1Ac-binding protein. Here, we further analyzed the potential role of PHB as Cry toxin receptor in comparison to cadherin (***), well recognized as Cry1Ac-receptor. HaPHB-2 midgut protein and HaCAD toxin binding region fragment (TBR) from H. armigera were expressed in Escherichia coli cells and binding assays with different Cry1 toxins were performed. We demonstrated that Cry1Ab, Cry1Ac and Cry1Fa toxins bound to HaPHB-2 similarly as to HaCAD-TBR. Different Cry1Ab mutant toxins located in domain II (Cry1AbF371A and Cry1AbG439D) or domain III (Cry1AbL511A and Cry1AbN514A), that were previously characterized to be affected in receptor binding, were analyzed regarding to their binding interaction with HaPHB-2 and toxicity against H. armigera.
    Moreover, overexpression of bHLH6 in an spx4 background did not affect the Pi content of spx4 under high- and low-P conditions. The bhlh6 spx4 double mutant showed lower shoot Pi concentrations and transcript levels of OsPT3 and OsPT10 compared with the spx4 mutant under high-P conditions. RNA sequencing results indicated that bHLH6 overexpression and spx4 mutant lines share many differentially expressed Pi-responsive genes. Therefore, bHLH6 is an important regulator for Pi signaling and homeostasis which antagonizes SPX4. This knowledge helps elucidate the molecular regulation of plant adaptation to Pi deficiency and will promote efforts toward the creation of low Pi-tolerant crops.Rab-interacting lysosomal protein (RILP) has been suggested to perform as a tumor suppressor in breast and prostate cancer cell lines. However, its expression profile and functional role in lung cancer have never been investigated. We applied the well-established cancer genomic database-The Cancer Genome Atlas to compare the RILP expression and methylation between lung cancer tissues and normal tissues. The potential correlation of RILP with clinical characteristics of lung cancer patients (e.g., stages, smoking, TP53, and methylation) was also be explored. Our results showed that the downregulation of RILP and upregulation of RILP methylation were identified in lung cancer tissues compared to normal healthy tissues. Downregulation of RILP was positively associated with lung cancer later stage (N3), smoking history, TP53 mutation, and poor prognosis, as well as inversely correlated with DNA (cytosine-5)-methyltransferase 1 (DNMT1) expression. Demethylation treatment enhanced RILP expression in lung cancer cells, suggesting hypermethylation is responsible for RILP silencing in lung cancer. https://www.selleckchem.com/products/ly2780301.html We further found that RILP depletion promoted lung cancer cell proliferation, migration, and invasion. We concluded that RILP acts as a tumor suppressor in lung cancer cells. Our results provided the theoretical basis for developing RILP-targeting or demethylating agents for lung cancer treatment.XynII is a family 11 glycoside hydrolase that uses the retaining mechanism for catalysis. In the active site, E177 works as the acid/base and E86 works as the nucleophile. Mutating an uncharged residue (N44) to an acidic residue (D) near E177 decreases the enzyme's optimal pH by ~ 1.0 unit. D44 was previously suggested to be a second proton carrier for catalysis. To test this hypothesis, we abolished the activity of E177 by mutating it to be Q, and mutated N44 to be D or E. These double mutants have dramatically decreased activities. Our high-resolution crystallographic structures and the microscopic pKa calculations show that D44 has similar position and pKa value during catalysis, indicating that D44 changes electrostatics around E177, which makes it prone to rotate as the acid/base in acidic conditions, thus decreases the pH optimum. Our results could be helpful to design enzymes with different pH optimum.Aminoacyl-tRNA synthetase-interacting multifunctional protein 2 (AIMP2) is a non-enzymatic component required for the multi-tRNA synthetase complex. While exon 2 skipping alternatively spliced variant of AIMP2 (AIMP2-DX2) compromises AIMP2 activity and is associated with carcinogenesis, its clinical potential awaits further validation. Here, we found that AIMP2-DX2/AIMP2 expression ratio is strongly correlated with major cancer signaling pathways and poor prognosis, particularly in acute myeloid leukemia (AML). Analysis of a clinical patient cohort revealed that AIMP2-DX2 positive AML patients show decreased overall survival and progression-free survival. We also developed targeted RNA-sequencing and single-molecule RNA-FISH tools to quantitatively analyze AIMP2-DX2/AIMP2 ratios at the single-cell level. By subclassifying hematologic cancer cells based on their AIMP2-DX2/AIMP2 ratios, we found that downregulating AIMP2-DX2 sensitizes cells to anticancer drugs only for a subgroup of cells while it has adverse effects on others. Collectively, our study establishes AIMP2-DX2 as a potential biomarker and a therapeutic target for hematologic cancer.The logical AND gate gene circuit based on the CRISPR-Cas9 system can distinguish bladder cancer cells from normal bladder epithelial cells. However, the layered artificial gene circuits have the problems of high complexity, difficulty in accurately predicting the behavior, and excessive redundancy, which cannot be applied to clinical translation. Here, we construct minigene circuits based on the CRISPReader, a technology used to control promoter-less gene expression in a robust manner. The minigene circuits significantly induce robust gene expression output in bladder cancer cells, but have nearly undetectable gene expression in normal bladder epithelial cells. The minigene circuits show a higher capability for cancer identification and intervention when compared with traditional gene circuits, and could be used for in vivo cancer gene therapy using the all-in-one AAV vector. This approach expands the design ideas and concepts of gene circuits in medical synthetic biology.Helicoverpa armigera is a major insect pest of several crops worldwide. This insect is susceptible to some Bacillus thuringiensis (Bt) Cry insecticidal proteins expressed in transgenic crops or used in biopesticides. Previously, we identified H. armigera prohibitin (PHB) as a Cry1Ac-binding protein. Here, we further analyzed the potential role of PHB as Cry toxin receptor in comparison to cadherin (CAD), well recognized as Cry1Ac-receptor. HaPHB-2 midgut protein and HaCAD toxin binding region fragment (TBR) from H. armigera were expressed in Escherichia coli cells and binding assays with different Cry1 toxins were performed. We demonstrated that Cry1Ab, Cry1Ac and Cry1Fa toxins bound to HaPHB-2 similarly as to HaCAD-TBR. Different Cry1Ab mutant toxins located in domain II (Cry1AbF371A and Cry1AbG439D) or domain III (Cry1AbL511A and Cry1AbN514A), that were previously characterized to be affected in receptor binding, were analyzed regarding to their binding interaction with HaPHB-2 and toxicity against H. armigera.
    0 Commentaires 0 Parts 199 Vue 0 Aperçu

  • 5 signaling pathway, accompanied with the influx of Na+ and Ca2+, which act as triggers for electrical remodeling.Long non-coding RNA TGFB2-antisense RNA1 (TGFB2-AS1) has been reported could regulate tumorigenesis. However, the roles of TGFB2-AS1 in lung adenocarcinoma (LUAD) remain largely unknown. In this work, we aimed to explore the expression levels of TGFB2-AS1 and mechanisms in regulating LUAD progression. Expression level of TGFB2-AS1 in LUAD tissues and normal tissues was analyzed at StarBase. Moreover, its expression in LUAD cells and normal cell was analyzed with quantitative real-time polymerase chain reaction method. Gain- and loss-of-function studies were conducted to analyze the biological roles of TGFB2-AS1 in LUAD. Results indicated TGFB2-AS1 was evidently downregulated in LUAD tissues and cells. Moreover, as analyzed by cell counting kit-8 assay, wound-healing and transwell invasion assays, results revealed TGFB2-AS1 overexpression could suppress proliferation, migration and invasion abilities of LUAD cells in vitro and tumor growth in vivo. In addition, LncBase V2.0 and TargetScan prediction tools showed TGFB2-AS1 and endothelin receptor type B (EDNRB) shares binding site in microRNA-340-5p (miR-340-5p). Furthermore, luciferase activity reporter assay and RT-qPCR assay validated these prediction results. Furthermore, we showed TGFB2-AS1 functions as sponge for miR-340-5p to regulate EDNRB expression. Collectively, our results indicated TGFB2-AS1/miR-340-5p/EDNRB axis plays crucial roles in regulating LUAD progression, indicating TGFB2-AS1 may be a novel therapeutic target for LUAD.Peripheral nerve injury (PNI)-induced neuropathic pain is a prevalent and severe clinical problem. It has been shown that microglia-mediated neuroinflammation plays a crucial role in neuropathic pain. The present study investigated the abnormal expression of C-X-C motif chemokine receptor type 2 (CXCR2) in a rat L5 spinal nerve ligation (SNL) model and evaluated the role of SB225002, a specific antagonist of CXCR2, in repressing neuroinflammation and neuropathic pain. It was found that CXCR2 expression was significantly upregulated in the dorsal horn of L5-SNL rats compared with sham control. Moreover, CXCR2 expression was increased in spinal microglia of rats after L5-SNL. Based on these results, the present study further examined whether pharmacological inhibition of CXCR2 suppressed microglial activation and neuropathic pain. It was demonstrated that SB225002 treatment inhibited L5-SNL-induced microglia proliferation and activation. Furthermore, SB225002 also significantly suppressed the L5-SNL-induced pro-inflammatory response, as indicated by decreased production of tumor necrosis factor-α, interleukin (IL)-1β and IL-6 in spinal cord tissues. The results indicated that SB225002 also significantly inhibited microglial cell viability and lipopolysaccharide-induced production of pro-inflammatory cytokines in cultured microglia. Functionally, SB225002 treatment effectively repressed mechanical and cold hypersensitivity after peripheral nerve injury. Collectively, the present results suggested that pharmacological inhibition of CXCR2 by SB225002 suppressed L5-SNL-induced neuroinflammation and neuropathic pain, thus offering a potential therapeutic strategy for neuropathic pain treatment.
    To establish a spinal cord injury (SCI) model by ventral violence and explore its pathological changes.

    We first designed and made a shape-suitable impinger. SD rats were divided into 4 groups according to force momentum calculated by weight and height Group A (350 g*28 cm), Group B (280 g*28 cm), Group C (210 g*28 cm), and Group D (sham, 0 g*0 cm). Then the anterior border of the rat's T11 centrum was hit by the by impinger via a free-falling method. Locomotor functional (Basso, Beattie and Bresnahan scale-BBB scale), GFAP expression and pathological changes, complications, and mortality were observed.

    The BBB scale scores were significantly different among all groups. Contusion, hematoma, and subarachnoid hemorrhage appeared at 1-6 h after injury in group A and B. Edema was obvious and the inflammatory cell infiltrated at the time of 6-48 h. Cicatricial contracture and porosis formed at 3-4 weeks, while group C only showed sporadic punctate hemorrhage. GFAP expression changed by time and location dynamically compared with group D. Various complications appeared in the experimental groups. Intestinal obstruction was the main cause of death. The mortality was significantly different among the groups (
    <0.05).

    The acute ventral closing SCI model could be set up successfully by a shape-suitable impinger. The procedure was simple and repetitive. https://www.selleckchem.com/products/amlexanox.html Neural function deficiency, pathological changes, and mortality were consistent with the injury controlled by coup momentum. Under the condition of this model, astrocytes went through an acute damage period and continued in the further hyperplasia stage.
    The acute ventral closing SCI model could be set up successfully by a shape-suitable impinger. The procedure was simple and repetitive. Neural function deficiency, pathological changes, and mortality were consistent with the injury controlled by coup momentum. Under the condition of this model, astrocytes went through an acute damage period and continued in the further hyperplasia stage.A high hepatitis B virus (HBV) load and chronic hepatitis B infection are well-recognized risk factors for the development of hepatocellular carcinoma (HCC), highlighting the need for research into the mechanisms underlying the role of HBV infection in HCC. Because phosphatase and tensin homolog (PTEN) has been implicated in HCC development, we explored whether PTEN has a role in HBV-related hepatocarcinogenesis. We found that PTEN expression was correlated with advanced clinicopathological features and that HBV infection exacerbates PTEN defects in HCC. Using an integrated approach, we then investigated if miRNAs linked HBV infection to PTEN downregulation in HCC and found that PTEN was a target of miR-181a/382/362/19a. We also show that miR-181a/382/362/19a-mediated inhibition of PTEN led to an enhanced malignant phenotype and stimulation of AKT signaling in HCC cells. Collectively, our results indicate that HBV infection exacerbates PTEN defects in hepatocellular carcinoma through upregulation of miR-181a/362/382/19a.
    5 signaling pathway, accompanied with the influx of Na+ and Ca2+, which act as triggers for electrical remodeling.Long non-coding RNA TGFB2-antisense RNA1 (TGFB2-AS1) has been reported could regulate tumorigenesis. However, the roles of TGFB2-AS1 in lung adenocarcinoma (LUAD) remain largely unknown. In this work, we aimed to explore the expression levels of TGFB2-AS1 and mechanisms in regulating LUAD progression. Expression level of TGFB2-AS1 in LUAD tissues and normal tissues was analyzed at StarBase. Moreover, its expression in LUAD cells and normal cell was analyzed with quantitative real-time polymerase chain reaction method. Gain- and loss-of-function studies were conducted to analyze the biological roles of TGFB2-AS1 in LUAD. Results indicated TGFB2-AS1 was evidently downregulated in LUAD tissues and cells. Moreover, as analyzed by cell counting kit-8 assay, wound-healing and transwell invasion assays, results revealed TGFB2-AS1 overexpression could suppress proliferation, migration and invasion abilities of LUAD cells in vitro and tumor growth in vivo. In addition, LncBase V2.0 and TargetScan prediction tools showed TGFB2-AS1 and endothelin receptor type B (EDNRB) shares binding site in microRNA-340-5p (miR-340-5p). Furthermore, luciferase activity reporter assay and RT-qPCR assay validated these prediction results. Furthermore, we showed TGFB2-AS1 functions as sponge for miR-340-5p to regulate EDNRB expression. Collectively, our results indicated TGFB2-AS1/miR-340-5p/EDNRB axis plays crucial roles in regulating LUAD progression, indicating TGFB2-AS1 may be a novel therapeutic target for LUAD.Peripheral nerve injury (PNI)-induced neuropathic pain is a prevalent and severe clinical problem. It has been shown that microglia-mediated neuroinflammation plays a crucial role in neuropathic pain. The present study investigated the abnormal expression of C-X-C motif chemokine receptor type 2 (CXCR2) in a rat L5 spinal nerve ligation (SNL) model and evaluated the role of SB225002, a specific antagonist of CXCR2, in repressing neuroinflammation and neuropathic pain. It was found that CXCR2 expression was significantly upregulated in the dorsal horn of L5-SNL rats compared with sham control. Moreover, CXCR2 expression was increased in spinal microglia of rats after L5-SNL. Based on these results, the present study further examined whether pharmacological inhibition of CXCR2 suppressed microglial activation and neuropathic pain. It was demonstrated that SB225002 treatment inhibited L5-SNL-induced microglia proliferation and activation. Furthermore, SB225002 also significantly suppressed the L5-SNL-induced pro-inflammatory response, as indicated by decreased production of tumor necrosis factor-α, interleukin (IL)-1β and IL-6 in spinal cord tissues. The results indicated that SB225002 also significantly inhibited microglial cell viability and lipopolysaccharide-induced production of pro-inflammatory cytokines in cultured microglia. Functionally, SB225002 treatment effectively repressed mechanical and cold hypersensitivity after peripheral nerve injury. Collectively, the present results suggested that pharmacological inhibition of CXCR2 by SB225002 suppressed L5-SNL-induced neuroinflammation and neuropathic pain, thus offering a potential therapeutic strategy for neuropathic pain treatment. To establish a spinal cord injury (SCI) model by ventral violence and explore its pathological changes. We first designed and made a shape-suitable impinger. SD rats were divided into 4 groups according to force momentum calculated by weight and height Group A (350 g*28 cm), Group B (280 g*28 cm), Group C (210 g*28 cm), and Group D (sham, 0 g*0 cm). Then the anterior border of the rat's T11 centrum was hit by the by impinger via a free-falling method. Locomotor functional (Basso, Beattie and Bresnahan scale-BBB scale), GFAP expression and pathological changes, complications, and mortality were observed. The BBB scale scores were significantly different among all groups. Contusion, hematoma, and subarachnoid hemorrhage appeared at 1-6 h after injury in group A and B. Edema was obvious and the inflammatory cell infiltrated at the time of 6-48 h. Cicatricial contracture and porosis formed at 3-4 weeks, while group C only showed sporadic punctate hemorrhage. GFAP expression changed by time and location dynamically compared with group D. Various complications appeared in the experimental groups. Intestinal obstruction was the main cause of death. The mortality was significantly different among the groups ( <0.05). The acute ventral closing SCI model could be set up successfully by a shape-suitable impinger. The procedure was simple and repetitive. https://www.selleckchem.com/products/amlexanox.html Neural function deficiency, pathological changes, and mortality were consistent with the injury controlled by coup momentum. Under the condition of this model, astrocytes went through an acute damage period and continued in the further hyperplasia stage. The acute ventral closing SCI model could be set up successfully by a shape-suitable impinger. The procedure was simple and repetitive. Neural function deficiency, pathological changes, and mortality were consistent with the injury controlled by coup momentum. Under the condition of this model, astrocytes went through an acute damage period and continued in the further hyperplasia stage.A high hepatitis B virus (HBV) load and chronic hepatitis B infection are well-recognized risk factors for the development of hepatocellular carcinoma (HCC), highlighting the need for research into the mechanisms underlying the role of HBV infection in HCC. Because phosphatase and tensin homolog (PTEN) has been implicated in HCC development, we explored whether PTEN has a role in HBV-related hepatocarcinogenesis. We found that PTEN expression was correlated with advanced clinicopathological features and that HBV infection exacerbates PTEN defects in HCC. Using an integrated approach, we then investigated if miRNAs linked HBV infection to PTEN downregulation in HCC and found that PTEN was a target of miR-181a/382/362/19a. We also show that miR-181a/382/362/19a-mediated inhibition of PTEN led to an enhanced malignant phenotype and stimulation of AKT signaling in HCC cells. Collectively, our results indicate that HBV infection exacerbates PTEN defects in hepatocellular carcinoma through upregulation of miR-181a/362/382/19a.
    0 Commentaires 0 Parts 117 Vue 0 Aperçu

  • We discuss theoretical implications of these findings for the role of ideology in social judgment and decision-making. (PsycInfo Database Record (c) 2020 APA, all rights reserved).Cognitively suppressing the retrieval of an unwanted memory causes its forgetting and, in the meantime, disrupts hippocampal functions. The present study investigated whether retrieval suppression induces virtual amnesia, which disturbs any existing memories that are reactivated in the temporal vicinity but are otherwise unrelated to the targets of suppression. Participants performed retrieval suppression on a set of memories while cues of an unrelated set of memories were briefly presented near in time to the suppression trials. Results showed that retrieval suppression impaired the retrieval of both the directly suppressed content and the reactivated unrelated memory. This amnesic shadow functioned in both the forward and backward temporal directions, and its forgetting effect was revealed by independent cues that were not presented in the shadow. Remarkably, a negative memory could be impaired simply by presenting it between the suppression episodes of an unrelated neutral memory. These findings provide support for systemic influence of retrieval suppression on hippocampal functions and offer a way to disrupt existing episodic memory strategically. (PsycInfo Database Record (c) 2020 APA, all rights reserved).The degree to which individuals engage in leisure activities has been shown to predict well-being in older adults, but it is not known whether such activities may help older adults maintain purposefulness into retirement. The current study sought to address whether activity engagement is associated with purpose in life and whether this association differs based on retirement status. We used data from three waves of the Health and Retirement Study between 2008 and 2016. Multilevel growth models accounted for both within- and between-person effects of leisure activity participation and retirement status on change in sense of purpose in life. Participants reported higher sense of purpose on occasions when they engaged more in leisure activities, and more active participants exhibited less decline in purpose over time. Retired individuals showed steeper declines in sense of purpose, but this effect was mitigated among participants reporting greater activity engagement. Leisure activity participation may help to support sense of purpose in life, particularly among retired individuals. These findings underscore the potential for leisure activity interventions to help older adults compensate for loss of work-related roles and maintain purposefulness into retirement. (PsycInfo Database Record (c) 2020 APA, all rights reserved).The present study examined whether subjective age is related to informant-rated cognition. Participants were adults (N = 2,337, mean age = 69.84 years, SD = 7.45) from the Health and Retirement Study who provided subjective age and demographic factors in 2008/2010 and informant-rated cognition in 2016 as part of the Harmonized Cognitive Assessment Protocol. An older subjective age was associated with informant reports of steeper cognitive decline, worse cognitive function, lower ability, and loss of ability to do everyday activities. The present study indicates that subjective age predicts cognitive function in everyday life as observed by knowledgeable informants. (PsycInfo Database Record (c) 2020 APA, all rights reserved).Statistical learning (SL) is the ability to generate predictions based on probabilistic dependencies in the environment, an ability that is present throughout life. The effect of aging on SL is still unclear. Here, we explore statistical learning in healthy adults (40 younger and 40 older). The novel paradigm tracks learning trajectories and shows age-related differences in overall performance, yet similarities in learning rates. Bayesian models reveal further differences between younger and older adults in dealing with uncertainty in this probabilistic SL task. We test computational models of 3 different learning strategies (a) Win-Stay, Lose-Shift, (b) Delta Rule Learning, (c) Information Weights to explore whether they capture age-related differences in performance and learning in the present task. A likely candidate mechanism emerges in the form of age-dependent differences in information weights, in which young adults more readily change their behavior, but also show disproportionally strong reactions toward erroneous predictions. With lower but more balanced information weights, older adults show slower behavioral adaptation but eventually arrive at more stable and accurate representations of the underlying transitional probability matrix. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
    Little is known about romantic relationship adjustment or perceptions of relationship quality (e.g., commitment and trust) among sexual minority persons with disabilities. The purpose of this study was to explore if collective self-esteem, disability adjustment, attachment styles, and cultural humility served as unique correlates and predictors of relationship adjustment and relationship quality among sexual minority persons (e.g., lesbian, gay, bisexual, queer) with disabilities.

    Ninety-two participants identifying as sexual minority persons living with a variety of disabilities (e.g., physical, psychiatric, medical, neurological), and who were partnered with sexual minority persons not living with a disability, were recruited using Amazon Mechanical Turk to complete an electronic questionnaire.

    Responses of 92 participants were analyzed using bivariate correlations and 3 separate blockwise hierarchical regression models. To varying degrees, collective self-esteem, attachment styles, and cultural humility served as significant correlates and predictors of dyadic adjustment, commitment, and trust.

    Implications for clinical practice and future research are discussed. Rehabilitation psychologists and other health care providers are encouraged to consider collective self-esteem, attachment styles, and cultural humility when working with sexual minority persons with disabilities in romantic relationships. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
    Implications for clinical practice and future research are discussed. Rehabilitation psychologists and other health care providers are encouraged to consider collective self-esteem, attachment styles, and cultural humility when working with sexual minority persons with disabilities in romantic relationships. https://www.selleckchem.com/products/lc-2.html (PsycInfo Database Record (c) 2021 APA, all rights reserved).
    We discuss theoretical implications of these findings for the role of ideology in social judgment and decision-making. (PsycInfo Database Record (c) 2020 APA, all rights reserved).Cognitively suppressing the retrieval of an unwanted memory causes its forgetting and, in the meantime, disrupts hippocampal functions. The present study investigated whether retrieval suppression induces virtual amnesia, which disturbs any existing memories that are reactivated in the temporal vicinity but are otherwise unrelated to the targets of suppression. Participants performed retrieval suppression on a set of memories while cues of an unrelated set of memories were briefly presented near in time to the suppression trials. Results showed that retrieval suppression impaired the retrieval of both the directly suppressed content and the reactivated unrelated memory. This amnesic shadow functioned in both the forward and backward temporal directions, and its forgetting effect was revealed by independent cues that were not presented in the shadow. Remarkably, a negative memory could be impaired simply by presenting it between the suppression episodes of an unrelated neutral memory. These findings provide support for systemic influence of retrieval suppression on hippocampal functions and offer a way to disrupt existing episodic memory strategically. (PsycInfo Database Record (c) 2020 APA, all rights reserved).The degree to which individuals engage in leisure activities has been shown to predict well-being in older adults, but it is not known whether such activities may help older adults maintain purposefulness into retirement. The current study sought to address whether activity engagement is associated with purpose in life and whether this association differs based on retirement status. We used data from three waves of the Health and Retirement Study between 2008 and 2016. Multilevel growth models accounted for both within- and between-person effects of leisure activity participation and retirement status on change in sense of purpose in life. Participants reported higher sense of purpose on occasions when they engaged more in leisure activities, and more active participants exhibited less decline in purpose over time. Retired individuals showed steeper declines in sense of purpose, but this effect was mitigated among participants reporting greater activity engagement. Leisure activity participation may help to support sense of purpose in life, particularly among retired individuals. These findings underscore the potential for leisure activity interventions to help older adults compensate for loss of work-related roles and maintain purposefulness into retirement. (PsycInfo Database Record (c) 2020 APA, all rights reserved).The present study examined whether subjective age is related to informant-rated cognition. Participants were adults (N = 2,337, mean age = 69.84 years, SD = 7.45) from the Health and Retirement Study who provided subjective age and demographic factors in 2008/2010 and informant-rated cognition in 2016 as part of the Harmonized Cognitive Assessment Protocol. An older subjective age was associated with informant reports of steeper cognitive decline, worse cognitive function, lower ability, and loss of ability to do everyday activities. The present study indicates that subjective age predicts cognitive function in everyday life as observed by knowledgeable informants. (PsycInfo Database Record (c) 2020 APA, all rights reserved).Statistical learning (SL) is the ability to generate predictions based on probabilistic dependencies in the environment, an ability that is present throughout life. The effect of aging on SL is still unclear. Here, we explore statistical learning in healthy adults (40 younger and 40 older). The novel paradigm tracks learning trajectories and shows age-related differences in overall performance, yet similarities in learning rates. Bayesian models reveal further differences between younger and older adults in dealing with uncertainty in this probabilistic SL task. We test computational models of 3 different learning strategies (a) Win-Stay, Lose-Shift, (b) Delta Rule Learning, (c) Information Weights to explore whether they capture age-related differences in performance and learning in the present task. A likely candidate mechanism emerges in the form of age-dependent differences in information weights, in which young adults more readily change their behavior, but also show disproportionally strong reactions toward erroneous predictions. With lower but more balanced information weights, older adults show slower behavioral adaptation but eventually arrive at more stable and accurate representations of the underlying transitional probability matrix. (PsycInfo Database Record (c) 2020 APA, all rights reserved). Little is known about romantic relationship adjustment or perceptions of relationship quality (e.g., commitment and trust) among sexual minority persons with disabilities. The purpose of this study was to explore if collective self-esteem, disability adjustment, attachment styles, and cultural humility served as unique correlates and predictors of relationship adjustment and relationship quality among sexual minority persons (e.g., lesbian, gay, bisexual, queer) with disabilities. Ninety-two participants identifying as sexual minority persons living with a variety of disabilities (e.g., physical, psychiatric, medical, neurological), and who were partnered with sexual minority persons not living with a disability, were recruited using Amazon Mechanical Turk to complete an electronic questionnaire. Responses of 92 participants were analyzed using bivariate correlations and 3 separate blockwise hierarchical regression models. To varying degrees, collective self-esteem, attachment styles, and cultural humility served as significant correlates and predictors of dyadic adjustment, commitment, and trust. Implications for clinical practice and future research are discussed. Rehabilitation psychologists and other health care providers are encouraged to consider collective self-esteem, attachment styles, and cultural humility when working with sexual minority persons with disabilities in romantic relationships. (PsycInfo Database Record (c) 2021 APA, all rights reserved). Implications for clinical practice and future research are discussed. Rehabilitation psychologists and other health care providers are encouraged to consider collective self-esteem, attachment styles, and cultural humility when working with sexual minority persons with disabilities in romantic relationships. https://www.selleckchem.com/products/lc-2.html (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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  • Liquid marbles are water droplets coated with solid particles that prevent coalescence and allow storage, transport, and handling of liquids in the form of a powder. Here, we report on the formation of liquid marbles that are stabilized entirely by a single monolayer of solid particles and thus minimize the amount of required solid material. As stabilizing particles, we synthesize relatively monodisperse, 80 μm-sized polystyrene (PS) particles coated with heptadecafluorooctanesulfonic acid-doped polypyrrole (PPy-C8F) shell (PS/PPy-C8F particles) by aqueous chemical oxidative seeded polymerization of pyrrole using FeCl3 as an oxidant and heptadecafluorooctanesulfonic acid as a hydrophobic dopant. We characterize the physicochemical properties of the particles as a function of the PPy-C8F loading. Laser diffraction particle size analyses of dilute aqueous suspensions indicate that the polymer particles disperse stably in water medium before and after coating with the PPy-C8F shell. X-ray photoelectron spectroscl LMs. Furthermore, the broadband light absorption properties of the PPy coating was used to control evaporation rate of the enclosed water phase on demand by irradiation with a near-infrared laser. The evaporation rate could be finely controlled by the thickness of the PPy-C8F shell of the particles stabilizing the liquid marbles.A series of optical and electron microscopies are utilized in concert to unravel the properties of corrugated metallic tips. While the overall microscopic shapes of the tips dictate their optical resonances and plasmonic field enhancement factors, nanometric structural details govern their tip-enhanced Raman (TER) spectra and images. Using 4-thiobenzonitrile (TBN) as a molecular reporter, spatially resolved TER spectra reveal that optical rectification and molecular charging are among the prominent observables in the tip-tip TER geometry. We show the spurious appearance of anions is driven by highly localized resonances that appear as a result of surface corrugation and their manifestation throughout the course of TER nanospectroscopy complicates spectral assignments. Overall, nanoscale spatial variations in the TERS spectra suggest that the tip-tip geometry sustains junction plasmons that appear very different from what may be expected from the hybridization of the bulk tip resonances.Networks of diffusively coupled inorganic oscillators, confined in nano- and microcompartments, are effective for predicting and understanding the global dynamics of those systems where the diffusion of activatory or inhibitory signals regulates the communication among different individuals. By taking advantage of a microfluidic device, we study the dynamics of arrays of diffusively coupled Belousov-Zhabotinsky (BZ) oscillators encapsulated in water-in-oil single emulsions. New synchronization patterns are induced and controlled by modulating the structural and chemical properties of the phospholipid-based biomimetic membranes via the introduction of specific dopants. Doping molecules do not alter the membrane basic backbone, but modify the lamellarity (and, in turn, the permeability) or interact chemically with the reaction intermediates. A transition from two-period clusters showing 12 period-locking to one-period antiphase synchronization is observed by decreasing the membrane lamellarity. An unsynchronized scenario is found when the dopant is able to interfere with chemical communication by reacting with the chemical messengers.Cleavage of strong C-O bonds without breaking C-C/C-H bonds is a key step for catalytic conversion of renewable biomass to hydrocarbon feedstocks. Herein we report multistep sequential engineering of orthogonal Lewis acid and palladium nanoparticle (NP) catalysts in a metal-organic framework (MOF) built from (Al-OH)n secondary building units and a mixture of 2,2'-bipyridine-5,5'-dicarboxylate (dcbpy) and 1,4-benzenediacrylate (pdac) ligands (1) for tandem C-O bond cleavage. Ozonolysis of 1 selectively removed pdac ligands to generate Al2(OH)(OH2) sites, which were subsequently triflated with trimethylsilyl triflate to afford strongly Lewis acidic sites for dehydroalkoxylation. Coordination of Pd(****)2Cl2 to dcbpy ligands followed by in situ reduction produced orthogonal Pd NP sites in 1-OTf-PdNP as the hydrogenation catalyst. The selective and precise transformation of 1 into 1-OTf-PdNP was characterized step by step using powder X-ray diffraction, transmission electron microscopy, thermogravimetric analysis, inductively coupled plasma mass spectrometry, infrared spectroscopy, and X-ray absorption spectroscopy. The hierarchical incorporation of orthogonal Lewis acid and Pd NP active sites endowed 1-OTf-PdNP with outstanding catalytic performance in apparent hydrogenolysis of etheric, alcoholic, and esteric C-O bonds to generate saturated alkanes via a tandem dehydroalkoxylation-hydrogenation process under relatively mild conditions. The reactivity of C-O bonds followed the trend of tertiary carbon > secondary carbon > primary carbon. Control experiments demonstrated the heterogeneous nature and recyclability of 1-OTf-PdNP and its superior catalytic activity over the homogeneous counterparts. Sequential engineering of multiple catalytic sites in MOFs thus presents a unique opportunity to address outstanding challenges in sustainable catalysis.Saccharopolyspora erythraea is used for industrial erythromycin production. To explore the physiological role of intracellular energy state in metabolic regulation by S. erythraea, we initially overexpressed the F1 part of the endogenous F1F0-ATPase in the high yielding erythromycin producing strain E3. The F1-ATPase expression resulted in lower [ATP]/[ADP] ratios, which was accompanied by a strong increase in the production of a reddish pigment and a decreased erythromycin production. Subsequent transcriptional analysis revealed that the lower intracellular [ATP]/[ADP] ratios exerted a pleotropic regulation on the metabolism of S. erythraea. https://www.selleckchem.com/products/epalrestat.html The lower [ATP]/[ADP] ratios induced physiological changes to restore the energy balance, mainly via pathways that tend to produce ATP or regenerate NADH. The F1-ATPase overexpression strain exhibited a state of redox stress, which was correlated to an alteration of electron transport at the branch of the terminal oxidases, and S. erythraea channeled the enhanced glycolytic flux toward a reddish pigment in order to reduce NADH formation.
    Liquid marbles are water droplets coated with solid particles that prevent coalescence and allow storage, transport, and handling of liquids in the form of a powder. Here, we report on the formation of liquid marbles that are stabilized entirely by a single monolayer of solid particles and thus minimize the amount of required solid material. As stabilizing particles, we synthesize relatively monodisperse, 80 μm-sized polystyrene (PS) particles coated with heptadecafluorooctanesulfonic acid-doped polypyrrole (PPy-C8F) shell (PS/PPy-C8F particles) by aqueous chemical oxidative seeded polymerization of pyrrole using FeCl3 as an oxidant and heptadecafluorooctanesulfonic acid as a hydrophobic dopant. We characterize the physicochemical properties of the particles as a function of the PPy-C8F loading. Laser diffraction particle size analyses of dilute aqueous suspensions indicate that the polymer particles disperse stably in water medium before and after coating with the PPy-C8F shell. X-ray photoelectron spectroscl LMs. Furthermore, the broadband light absorption properties of the PPy coating was used to control evaporation rate of the enclosed water phase on demand by irradiation with a near-infrared laser. The evaporation rate could be finely controlled by the thickness of the PPy-C8F shell of the particles stabilizing the liquid marbles.A series of optical and electron microscopies are utilized in concert to unravel the properties of corrugated metallic tips. While the overall microscopic shapes of the tips dictate their optical resonances and plasmonic field enhancement factors, nanometric structural details govern their tip-enhanced Raman (TER) spectra and images. Using 4-thiobenzonitrile (TBN) as a molecular reporter, spatially resolved TER spectra reveal that optical rectification and molecular charging are among the prominent observables in the tip-tip TER geometry. We show the spurious appearance of anions is driven by highly localized resonances that appear as a result of surface corrugation and their manifestation throughout the course of TER nanospectroscopy complicates spectral assignments. Overall, nanoscale spatial variations in the TERS spectra suggest that the tip-tip geometry sustains junction plasmons that appear very different from what may be expected from the hybridization of the bulk tip resonances.Networks of diffusively coupled inorganic oscillators, confined in nano- and microcompartments, are effective for predicting and understanding the global dynamics of those systems where the diffusion of activatory or inhibitory signals regulates the communication among different individuals. By taking advantage of a microfluidic device, we study the dynamics of arrays of diffusively coupled Belousov-Zhabotinsky (BZ) oscillators encapsulated in water-in-oil single emulsions. New synchronization patterns are induced and controlled by modulating the structural and chemical properties of the phospholipid-based biomimetic membranes via the introduction of specific dopants. Doping molecules do not alter the membrane basic backbone, but modify the lamellarity (and, in turn, the permeability) or interact chemically with the reaction intermediates. A transition from two-period clusters showing 12 period-locking to one-period antiphase synchronization is observed by decreasing the membrane lamellarity. An unsynchronized scenario is found when the dopant is able to interfere with chemical communication by reacting with the chemical messengers.Cleavage of strong C-O bonds without breaking C-C/C-H bonds is a key step for catalytic conversion of renewable biomass to hydrocarbon feedstocks. Herein we report multistep sequential engineering of orthogonal Lewis acid and palladium nanoparticle (NP) catalysts in a metal-organic framework (MOF) built from (Al-OH)n secondary building units and a mixture of 2,2'-bipyridine-5,5'-dicarboxylate (dcbpy) and 1,4-benzenediacrylate (pdac) ligands (1) for tandem C-O bond cleavage. Ozonolysis of 1 selectively removed pdac ligands to generate Al2(OH)(OH2) sites, which were subsequently triflated with trimethylsilyl triflate to afford strongly Lewis acidic sites for dehydroalkoxylation. Coordination of Pd(MeCN)2Cl2 to dcbpy ligands followed by in situ reduction produced orthogonal Pd NP sites in 1-OTf-PdNP as the hydrogenation catalyst. The selective and precise transformation of 1 into 1-OTf-PdNP was characterized step by step using powder X-ray diffraction, transmission electron microscopy, thermogravimetric analysis, inductively coupled plasma mass spectrometry, infrared spectroscopy, and X-ray absorption spectroscopy. The hierarchical incorporation of orthogonal Lewis acid and Pd NP active sites endowed 1-OTf-PdNP with outstanding catalytic performance in apparent hydrogenolysis of etheric, alcoholic, and esteric C-O bonds to generate saturated alkanes via a tandem dehydroalkoxylation-hydrogenation process under relatively mild conditions. The reactivity of C-O bonds followed the trend of tertiary carbon > secondary carbon > primary carbon. Control experiments demonstrated the heterogeneous nature and recyclability of 1-OTf-PdNP and its superior catalytic activity over the homogeneous counterparts. Sequential engineering of multiple catalytic sites in MOFs thus presents a unique opportunity to address outstanding challenges in sustainable catalysis.Saccharopolyspora erythraea is used for industrial erythromycin production. To explore the physiological role of intracellular energy state in metabolic regulation by S. erythraea, we initially overexpressed the F1 part of the endogenous F1F0-ATPase in the high yielding erythromycin producing strain E3. The F1-ATPase expression resulted in lower [ATP]/[ADP] ratios, which was accompanied by a strong increase in the production of a reddish pigment and a decreased erythromycin production. Subsequent transcriptional analysis revealed that the lower intracellular [ATP]/[ADP] ratios exerted a pleotropic regulation on the metabolism of S. erythraea. https://www.selleckchem.com/products/epalrestat.html The lower [ATP]/[ADP] ratios induced physiological changes to restore the energy balance, mainly via pathways that tend to produce ATP or regenerate NADH. The F1-ATPase overexpression strain exhibited a state of redox stress, which was correlated to an alteration of electron transport at the branch of the terminal oxidases, and S. erythraea channeled the enhanced glycolytic flux toward a reddish pigment in order to reduce NADH formation.
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  • Osteoarthritis (OA) is a degenerative disease resulting in irreversible, progressive destruction of articular cartilage1. The etiology of OA is complex and involves a variety of factors, including genetic predisposition, acute injury and chronic inflammation2-4. Here we investigate the ability of resident skeletal stem-cell (SSC) populations to regenerate cartilage in relation to age, a possible contributor to the development of osteoarthritis5-7. We demonstrate that aging is associated with progressive loss of SSCs and diminished chondrogenesis in the joints of both **** and humans. However, a local expansion of SSCs could still be triggered in the chondral surface of adult limb joints in **** by stimulating a regenerative response using microfracture (MF) surgery. Although MF-activated SSCs tended to form fibrous tissues, localized co-delivery of BMP2 and soluble VEGFR1 (sVEGFR1), a VEGF receptor antagonist, in a hydrogel skewed differentiation of MF-activated SSCs toward articular cartilage. These data indicate that following MF, a resident stem-cell population can be induced to generate cartilage for treatment of localized chondral disease in OA.The global burden of diabetes is rapidly increasing, from 451 million people in 2019 to 693 million by 20451. The insidious onset of type 2 diabetes delays diagnosis and increases morbidity2. Given the multifactorial vascular effects of diabetes, we hypothesized that smartphone-based photoplethysmography could provide a widely accessible digital biomarker for diabetes. Here we developed a deep neural network (DNN) to detect prevalent diabetes using smartphone-based photoplethysmography from an initial cohort of 53,870 individuals (the 'primary cohort'), which we then validated in a separate cohort of 7,806 individuals (the 'contemporary cohort') and a cohort of 181 prospectively enrolled individuals from three clinics (the 'clinic cohort'). The DNN achieved an area under the curve for prevalent diabetes of 0.766 in the primary cohort (95% confidence interval 0.750-0.782; sensitivity 75%, specificity 65%) and 0.740 in the contemporary cohort (95% confidence interval 0.723-0.758; sensitivity 81%, specificity 54%). When the output of the DNN, called the DNN score, was included in a regression analysis alongside age, gender, race/ethnicity and body mass index, the area under the curve was 0.830 and the DNN score remained independently predictive of diabetes. The performance of the DNN in the clinic cohort was similar to that in other validation datasets. There was a significant and positive association between the continuous DNN score and hemoglobin A1c (P ≤ 0.001) among those with hemoglobin A1c data. These findings demonstrate that smartphone-based photoplethysmography provides a readily attainable, non-invasive digital biomarker of prevalent diabetes.Use of wearable devices that monitor physical activity is projected to increase more than fivefold per half-decade1. We investigated how device-based physical activity energy expenditure (PAEE) and different intensity profiles were associated with all-cause mortality. We used a network harmonization approach to map dominant-wrist acceleration to PAEE in 96,476 UK Biobank participants (mean age 62 years, 56% female). We also calculated the fraction of PAEE accumulated from moderate-to-vigorous-intensity physical activity (MVPA). Over the median 3.1-year follow-up period (302,526 person-years), 732 deaths were recorded. Higher PAEE was associated with a lower hazard of all-cause mortality for a constant fraction of MVPA (for example, 21% (95% confidence interval 4-35%) lower hazard for 20 versus 15 kJ kg-1 d-1 PAEE with 10% from MVPA). Similarly, a higher MVPA fraction was associated with a lower hazard when PAEE remained constant (for example, 30% (8-47%) lower hazard when 20% versus 10% of a fixed 15 kJ kg-1 d-1 PAEE volume was from MVPA). Our results show that higher volumes of PAEE are associated with reduced mortality rates, and achieving the same volume through higher-intensity activity is associated with greater reductions than through lower-intensity activity. The linkage of device-measured activity to energy expenditure creates a framework for using wearables for personalized prevention.High-resolution X-ray microcomputed tomography, or microCT (μCT), enables the digital imaging of whole objects in three dimensions. The power of μCT to visualize internal features without disarticulation makes it particularly valuable for the study of museum collections, which house millions of physical specimens documenting the spatio-temporal patterns of life. Despite the potential for comparative analyses, most μCT studies include limited numbers of museum specimens, due to the challenges of digitizing numerous individuals within a project scope. https://www.selleckchem.com/products/ttnpb-arotinoid-acid.html Here we describe a method for high-throughput μCT scanning of hundreds of small ( less then  2 cm) specimens in a single container, followed by individual labelling and archival storage. We also explore the effects of various packing materials and multiple specimens per capsule to minimize sample movement that can degrade image quality, and hence μCT investment. We demonstrate this protocol on vertebrate fossils from Queensland Museum, Australia, as part of an effort to track community responses to climate change over evolutionary time. This system can be easily modified for other types of wet and dry material amenable to X-ray attenuation, including geological, botanical and zoological samples, providing greater access to large-scale phenotypic data and adding value to global collections.Regulated fibroblast growth factor (FGF) signalling is a prerequisite for the correct development and homeostasis of articular cartilage, as evidenced by the fact that aberrant FGF signalling contributes to the maldevelopment of joints and to the onset and progression of osteoarthritis. Of the four FGF receptors (FGFRs 1-4), FGFR1 and FGFR3 are strongly implicated in osteoarthritis, and FGFR1 antagonists, as well as agonists of FGFR3, have shown therapeutic efficacy in mouse models of spontaneous and surgically induced osteoarthritis. FGF18, a high affinity ligand for FGFR3, is the only FGF-based drug currently in clinical trials for osteoarthritis. This Review covers the latest advances in our understanding of the molecular mechanisms that regulate FGF signalling during normal joint development and in the pathogenesis of osteoarthritis. Strategies for FGF signalling-based treatment of osteoarthritis and for cartilage repair in animal models and clinical trials are also introduced. An improved understanding of FGF signalling from a structural biology perspective, and of its roles in skeletal development and diseases, could unlock new avenues for discovery of modulators of FGF signalling that can slow or stop the progression of osteoarthritis.
    Osteoarthritis (OA) is a degenerative disease resulting in irreversible, progressive destruction of articular cartilage1. The etiology of OA is complex and involves a variety of factors, including genetic predisposition, acute injury and chronic inflammation2-4. Here we investigate the ability of resident skeletal stem-cell (SSC) populations to regenerate cartilage in relation to age, a possible contributor to the development of osteoarthritis5-7. We demonstrate that aging is associated with progressive loss of SSCs and diminished chondrogenesis in the joints of both mice and humans. However, a local expansion of SSCs could still be triggered in the chondral surface of adult limb joints in mice by stimulating a regenerative response using microfracture (MF) surgery. Although MF-activated SSCs tended to form fibrous tissues, localized co-delivery of BMP2 and soluble VEGFR1 (sVEGFR1), a VEGF receptor antagonist, in a hydrogel skewed differentiation of MF-activated SSCs toward articular cartilage. These data indicate that following MF, a resident stem-cell population can be induced to generate cartilage for treatment of localized chondral disease in OA.The global burden of diabetes is rapidly increasing, from 451 million people in 2019 to 693 million by 20451. The insidious onset of type 2 diabetes delays diagnosis and increases morbidity2. Given the multifactorial vascular effects of diabetes, we hypothesized that smartphone-based photoplethysmography could provide a widely accessible digital biomarker for diabetes. Here we developed a deep neural network (DNN) to detect prevalent diabetes using smartphone-based photoplethysmography from an initial cohort of 53,870 individuals (the 'primary cohort'), which we then validated in a separate cohort of 7,806 individuals (the 'contemporary cohort') and a cohort of 181 prospectively enrolled individuals from three clinics (the 'clinic cohort'). The DNN achieved an area under the curve for prevalent diabetes of 0.766 in the primary cohort (95% confidence interval 0.750-0.782; sensitivity 75%, specificity 65%) and 0.740 in the contemporary cohort (95% confidence interval 0.723-0.758; sensitivity 81%, specificity 54%). When the output of the DNN, called the DNN score, was included in a regression analysis alongside age, gender, race/ethnicity and body mass index, the area under the curve was 0.830 and the DNN score remained independently predictive of diabetes. The performance of the DNN in the clinic cohort was similar to that in other validation datasets. There was a significant and positive association between the continuous DNN score and hemoglobin A1c (P ≤ 0.001) among those with hemoglobin A1c data. These findings demonstrate that smartphone-based photoplethysmography provides a readily attainable, non-invasive digital biomarker of prevalent diabetes.Use of wearable devices that monitor physical activity is projected to increase more than fivefold per half-decade1. We investigated how device-based physical activity energy expenditure (PAEE) and different intensity profiles were associated with all-cause mortality. We used a network harmonization approach to map dominant-wrist acceleration to PAEE in 96,476 UK Biobank participants (mean age 62 years, 56% female). We also calculated the fraction of PAEE accumulated from moderate-to-vigorous-intensity physical activity (MVPA). Over the median 3.1-year follow-up period (302,526 person-years), 732 deaths were recorded. Higher PAEE was associated with a lower hazard of all-cause mortality for a constant fraction of MVPA (for example, 21% (95% confidence interval 4-35%) lower hazard for 20 versus 15 kJ kg-1 d-1 PAEE with 10% from MVPA). Similarly, a higher MVPA fraction was associated with a lower hazard when PAEE remained constant (for example, 30% (8-47%) lower hazard when 20% versus 10% of a fixed 15 kJ kg-1 d-1 PAEE volume was from MVPA). Our results show that higher volumes of PAEE are associated with reduced mortality rates, and achieving the same volume through higher-intensity activity is associated with greater reductions than through lower-intensity activity. The linkage of device-measured activity to energy expenditure creates a framework for using wearables for personalized prevention.High-resolution X-ray microcomputed tomography, or microCT (μCT), enables the digital imaging of whole objects in three dimensions. The power of μCT to visualize internal features without disarticulation makes it particularly valuable for the study of museum collections, which house millions of physical specimens documenting the spatio-temporal patterns of life. Despite the potential for comparative analyses, most μCT studies include limited numbers of museum specimens, due to the challenges of digitizing numerous individuals within a project scope. https://www.selleckchem.com/products/ttnpb-arotinoid-acid.html Here we describe a method for high-throughput μCT scanning of hundreds of small ( less then  2 cm) specimens in a single container, followed by individual labelling and archival storage. We also explore the effects of various packing materials and multiple specimens per capsule to minimize sample movement that can degrade image quality, and hence μCT investment. We demonstrate this protocol on vertebrate fossils from Queensland Museum, Australia, as part of an effort to track community responses to climate change over evolutionary time. This system can be easily modified for other types of wet and dry material amenable to X-ray attenuation, including geological, botanical and zoological samples, providing greater access to large-scale phenotypic data and adding value to global collections.Regulated fibroblast growth factor (FGF) signalling is a prerequisite for the correct development and homeostasis of articular cartilage, as evidenced by the fact that aberrant FGF signalling contributes to the maldevelopment of joints and to the onset and progression of osteoarthritis. Of the four FGF receptors (FGFRs 1-4), FGFR1 and FGFR3 are strongly implicated in osteoarthritis, and FGFR1 antagonists, as well as agonists of FGFR3, have shown therapeutic efficacy in mouse models of spontaneous and surgically induced osteoarthritis. FGF18, a high affinity ligand for FGFR3, is the only FGF-based drug currently in clinical trials for osteoarthritis. This Review covers the latest advances in our understanding of the molecular mechanisms that regulate FGF signalling during normal joint development and in the pathogenesis of osteoarthritis. Strategies for FGF signalling-based treatment of osteoarthritis and for cartilage repair in animal models and clinical trials are also introduced. An improved understanding of FGF signalling from a structural biology perspective, and of its roles in skeletal development and diseases, could unlock new avenues for discovery of modulators of FGF signalling that can slow or stop the progression of osteoarthritis.
    0 Commentaires 0 Parts 136 Vue 0 Aperçu

  • Invitro, TNF-α and IL-1β decreased BSEP and CYP7A1 while increasing miRNA-34a-5p and miRNA 222-3p. LXR, SHP, CYP7A1, NTCP, and MRP2 were decreased by miRNA-34a-5p, whereas miRNA-222-3p decreased NTCP and MRP4. TNF-α and IL-1β increased expression of miRNAs 34a-5p and 222-3p and these miRNAs then decrease expression of multiple bile acid transporters and nuclear receptors.

    Loss of bile acid transporters increases hepatotoxicity via bile acid retention. Therapeutic agents that increase bile acid transport or nuclear receptor functioning should be investigated in BA.
    Loss of bile acid transporters increases hepatotoxicity via bile acid retention. https://www.selleckchem.com/products/epalrestat.html Therapeutic agents that increase bile acid transport or nuclear receptor functioning should be investigated in BA.
    Grand rounds is an important and traditional academic medical institution. With generational changes in learning and the advancement of technology, it is difficult to know if the current method of grand rounds remains relevant and is meeting its audience's needs. Furthermore, surgeons may have different educational needs for grand rounds than other fields of healthcare. This study evaluates the needs of attendees and their attitudes toward modern surgical grand rounds through focus groups.

    Independent focus groups were conducted in the department of surgery at a large academic institution. In total, 19 individuals (five professors, three associate professors, three assistant professors, seven senior residents, and one junior resident) participated in the focus groups. Thematic analysis was conducted through a process of independent coding and defining of themes followed by joint revision until consensus was reached.

    Four major themes arose from the discussion current design and format of grand rounds, a to meaningful grand rounds. This first and interesting research into surgery grand rounds provides insight on how to best meet attendee needs in the 21st century.The autophagic pathway involves the encapsulation of substrates in double-membraned vesicles, which are subsequently delivered to the lysosome for enzymatic degradation and recycling of metabolic precursors. Autophagy is a major cellular defense against oxidative stress, or related conditions that cause accumulation of damaged proteins or organelles. Selective forms of autophagy can maintain organelle populations or remove aggregated proteins. Dysregulation of redox homeostasis under pathological conditions results in excessive generation of reactive oxygen species (ROS), leading to oxidative stress and the associated oxidative damage of cellular components. Accumulating evidence indicates that autophagy is necessary to maintain redox homeostasis. ROS activates autophagy, which facilitates cellular adaptation and diminishes oxidative damage by degrading and recycling intracellular damaged macromolecules and dysfunctional organelles. The cellular responses triggered by oxidative stress include the altered regulation of signaling pathways that culminate in the regulation of autophagy. Current research suggests a central role for autophagy as a mammalian oxidative stress response and its interrelationship to other stress defense systems. Altered autophagy phenotypes have been observed in lung diseases such as chronic obstructive lung disease, acute lung injury, cystic fibrosis, idiopathic pulmonary fibrosis, and pulmonary arterial hypertension, and asthma. Understanding the mechanisms by which ROS regulate autophagy will provide novel therapeutic targets for lung diseases. This review highlights our current understanding on the interplay between ROS and autophagy in the development of pulmonary disease.NADPH oxidases produce reactive oxygen species that differ in localization, type and concentration. Within the Nox family only Nox4 produces H2O2 which can directly oxidize cysteine residues. With this post-translational modification, activity, stability, localization and protein-protein interactions of the affected protein is altered. Nox4 controls differentiation, cellular homeostasis and prevents inflammation. Therefore, is likely that epigenetic mechanisms contribute to the effects of Nox4. One group of epigenetic modifiers are class IIa histone deacetylases (HDACs). We hypothesize that Nox4-derived H2O2 oxidizes HDACs and analyzed whether HDACs can be differentially oxidized by Nox4. As an artificial system, we utilized HEK293 cells, overexpressing Nox4 in a tetracycline-inducible manner. HDAC4 was oxidized upon Nox4 overexpression. Additionally, Nox4 overexpression increased HDAC4 phosphorylation on Ser632. H2O2 disrupted HDAC4/Mef2A complex, which de-represses Mef2A. In endothelial cells such as HUVECs and HMECs, overexpression of HDAC4 significantly reduced tube formation. Overexpression of a redox insensitive HDAC4 had no effect on endothelial tube formation. Treatment with H2O2, induction of Nox4 expression by treatment of the cells with TGFβ and co-overexpression of Nox4 not only induced phosphorylation of HDAC4, but also restored the repressive effect of HDAC4 for tube formation, while overexpression of a redox dead mutant of Nox4 did not. Taken together, Nox4 oxidizes HDAC4, increases its phosphorylation, and eventually ensures proper tube formation by endothelial cells.
    To identify time trends in incidence, mortality and 5-year relative survival in children and adolescents with cancer in Goiania-Goias, Brazil, during the years of 1996-2012.

    Incidence and mortality age-standardized rates (ASR) were calculated, and trends were identified by determining the Average Annual Percentage Change (AAPC). Five-year relative survival were estimated.

    The overall incidence ASR (1996-2012) was 164.2/1,000,000 in both genders. In boys was 176.6/1,000,000, in girls it was 151.8/1,000,000. Overall mortality ASR for both gender were 69.3/1,000,000. Incidence rates (AAPC -0.5; 95 %CI -2.4;1.4) and mortality rates (AAPC 0.0; 95 %CI -2.6;2;7) were stable in the period. Five-year relative survival for all cancers were 63.9 %, with the highest survival rates for retinobastoma (83.5 %), germ cell tumors (79.8 %), and lymphomas (72.7 %). It was observed an increase in survival in the period from de 62.8 % (1996 a 2003) to 65.0 % from 2004 to 2012.

    Children and adolescent cancer incidence and mortality rates were higher in Goiania, but both are stable overall.
    Invitro, TNF-α and IL-1β decreased BSEP and CYP7A1 while increasing miRNA-34a-5p and miRNA 222-3p. LXR, SHP, CYP7A1, NTCP, and MRP2 were decreased by miRNA-34a-5p, whereas miRNA-222-3p decreased NTCP and MRP4. TNF-α and IL-1β increased expression of miRNAs 34a-5p and 222-3p and these miRNAs then decrease expression of multiple bile acid transporters and nuclear receptors. Loss of bile acid transporters increases hepatotoxicity via bile acid retention. Therapeutic agents that increase bile acid transport or nuclear receptor functioning should be investigated in BA. Loss of bile acid transporters increases hepatotoxicity via bile acid retention. https://www.selleckchem.com/products/epalrestat.html Therapeutic agents that increase bile acid transport or nuclear receptor functioning should be investigated in BA. Grand rounds is an important and traditional academic medical institution. With generational changes in learning and the advancement of technology, it is difficult to know if the current method of grand rounds remains relevant and is meeting its audience's needs. Furthermore, surgeons may have different educational needs for grand rounds than other fields of healthcare. This study evaluates the needs of attendees and their attitudes toward modern surgical grand rounds through focus groups. Independent focus groups were conducted in the department of surgery at a large academic institution. In total, 19 individuals (five professors, three associate professors, three assistant professors, seven senior residents, and one junior resident) participated in the focus groups. Thematic analysis was conducted through a process of independent coding and defining of themes followed by joint revision until consensus was reached. Four major themes arose from the discussion current design and format of grand rounds, a to meaningful grand rounds. This first and interesting research into surgery grand rounds provides insight on how to best meet attendee needs in the 21st century.The autophagic pathway involves the encapsulation of substrates in double-membraned vesicles, which are subsequently delivered to the lysosome for enzymatic degradation and recycling of metabolic precursors. Autophagy is a major cellular defense against oxidative stress, or related conditions that cause accumulation of damaged proteins or organelles. Selective forms of autophagy can maintain organelle populations or remove aggregated proteins. Dysregulation of redox homeostasis under pathological conditions results in excessive generation of reactive oxygen species (ROS), leading to oxidative stress and the associated oxidative damage of cellular components. Accumulating evidence indicates that autophagy is necessary to maintain redox homeostasis. ROS activates autophagy, which facilitates cellular adaptation and diminishes oxidative damage by degrading and recycling intracellular damaged macromolecules and dysfunctional organelles. The cellular responses triggered by oxidative stress include the altered regulation of signaling pathways that culminate in the regulation of autophagy. Current research suggests a central role for autophagy as a mammalian oxidative stress response and its interrelationship to other stress defense systems. Altered autophagy phenotypes have been observed in lung diseases such as chronic obstructive lung disease, acute lung injury, cystic fibrosis, idiopathic pulmonary fibrosis, and pulmonary arterial hypertension, and asthma. Understanding the mechanisms by which ROS regulate autophagy will provide novel therapeutic targets for lung diseases. This review highlights our current understanding on the interplay between ROS and autophagy in the development of pulmonary disease.NADPH oxidases produce reactive oxygen species that differ in localization, type and concentration. Within the Nox family only Nox4 produces H2O2 which can directly oxidize cysteine residues. With this post-translational modification, activity, stability, localization and protein-protein interactions of the affected protein is altered. Nox4 controls differentiation, cellular homeostasis and prevents inflammation. Therefore, is likely that epigenetic mechanisms contribute to the effects of Nox4. One group of epigenetic modifiers are class IIa histone deacetylases (HDACs). We hypothesize that Nox4-derived H2O2 oxidizes HDACs and analyzed whether HDACs can be differentially oxidized by Nox4. As an artificial system, we utilized HEK293 cells, overexpressing Nox4 in a tetracycline-inducible manner. HDAC4 was oxidized upon Nox4 overexpression. Additionally, Nox4 overexpression increased HDAC4 phosphorylation on Ser632. H2O2 disrupted HDAC4/Mef2A complex, which de-represses Mef2A. In endothelial cells such as HUVECs and HMECs, overexpression of HDAC4 significantly reduced tube formation. Overexpression of a redox insensitive HDAC4 had no effect on endothelial tube formation. Treatment with H2O2, induction of Nox4 expression by treatment of the cells with TGFβ and co-overexpression of Nox4 not only induced phosphorylation of HDAC4, but also restored the repressive effect of HDAC4 for tube formation, while overexpression of a redox dead mutant of Nox4 did not. Taken together, Nox4 oxidizes HDAC4, increases its phosphorylation, and eventually ensures proper tube formation by endothelial cells. To identify time trends in incidence, mortality and 5-year relative survival in children and adolescents with cancer in Goiania-Goias, Brazil, during the years of 1996-2012. Incidence and mortality age-standardized rates (ASR) were calculated, and trends were identified by determining the Average Annual Percentage Change (AAPC). Five-year relative survival were estimated. The overall incidence ASR (1996-2012) was 164.2/1,000,000 in both genders. In boys was 176.6/1,000,000, in girls it was 151.8/1,000,000. Overall mortality ASR for both gender were 69.3/1,000,000. Incidence rates (AAPC -0.5; 95 %CI -2.4;1.4) and mortality rates (AAPC 0.0; 95 %CI -2.6;2;7) were stable in the period. Five-year relative survival for all cancers were 63.9 %, with the highest survival rates for retinobastoma (83.5 %), germ cell tumors (79.8 %), and lymphomas (72.7 %). It was observed an increase in survival in the period from de 62.8 % (1996 a 2003) to 65.0 % from 2004 to 2012. Children and adolescent cancer incidence and mortality rates were higher in Goiania, but both are stable overall.
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  • No correlation was found between diurnal preference/sleep habits with anxiety symptoms for both BAI total score and its factors. However, women with PER3
    genotype showed less interpesonal affect in depression symptomatology and more anxiety symptoms in four factors of the BAI questionnaire.

    Mainly because this study was based on self-report questionnaires and was limited to undergraduate students aging 18 to 30 years old.

    These results reinforce a role for sleep and diurnal preference in depression, and PER3 VNTR polymorphism in anxiety symptomatology, particularly in women.
    These results reinforce a role for sleep and diurnal preference in depression, and PER3 VNTR polymorphism in anxiety symptomatology, particularly in women.
    Suicidality is common in patients with migraine. Here, we performed a systematic review and estimated the prevalence of suicidal ideation (SI) and suicide attempt (SA) in patients with migraine.

    We searched Pubmed, Embase, Web of Science, Cochrane database library, CINAHL, and PsycINFO for relevant publications. A random-effects model was used to pool the estimates of the prevalence of SI and SA, which were also stratified by the geographical location of the research institutions from the studies included in this meta-analysis.

    Fifteen studies involving 2,247,648 participants with migraine were selected. Pooled prevalence estimates of SI and SA were 15.5% [95% confidence interval (CI) 10.4-21.3%] and 3.9% (95% CI 0.9-8.8%), respectively, and the prevalence of SI was higher in Asian countries (21.5%, 95%CI 16.8-26.6%) compared with non-Asian countries (11.0%, 95%CI 6.1-17.2%). Measures of heterogeneity between studies were high for all outcomes (I
    =89-100%), indicating that the substantial between-study heterogeneity in estimated proportions was not attributed to sampling error. The leave-one-out analysis showed that no single study significantly affected the final pooled results.

    This meta-analysis indicated a high prevalence of SI and SA in migraine patients. Thus, it is necessary to design targeted preventive measures for the management of migraine-related suicide.
    This meta-analysis indicated a high prevalence of SI and SA in migraine patients. Thus, it is necessary to design targeted preventive measures for the management of migraine-related suicide.Within the context of school-based physical education (PE), a strength and conditioning program called CrossFit Kids (CFK) has emerged as a potential intervention for positively impacting students. The purpose of this study was to evaluate through a randomized-controlled trial how academic and health-related fitness outcomes differed for middle school students (age = 12.73; 55.3 % male) who participated in a school-based CFK program (n=72) as compared to a group of students who participated in PE class (n=72). Questionnaire data were collected twice across the 9-month academic year and combined with FitnessGram and grade data. Students in both the intervention and comparison groups increased in health-related fitness outcomes (all p values less then .017), and there was a significant treatment group by time interaction on school-reported grades [F(1, 124) = 7.270, p = .008, η_P^2 = .055]. Significant gender by time interaction effects were found for the relationship between CFK or PE participation and health-related fitness outcomes, but there were no significant interaction effects by gender on academic outcomes. Because developmental outcomes are conditional and result from the coaction of many factors, the findings suggest that some elements of CFK might be beneficial to build skills yet disadvantageous to academic outcomes.Herein we report on a patient acutely admitted to the emergency room due to malaise and effort intolerance. A heart ultrasound, a cardiovascular MRI and an endomyocardial biopsy were suggestive of myocarditis. With appropriate medications the ejection fraction (EF) slowly improved but follow-up blood examinations revealed a hyperckemia. A neuromuscular examination revealed bilateral atrophy of medial gastrocnemius muscle and absent deep tendon reflexes at lower limbs . Genetic analysis revealed the presence of the hemizygous novel mutation c.757delT (p.Trp253fs) in XK gene thus confirming the diagnosis of McLeod Syndrome (MLS). https://www.selleckchem.com/products/ly2780301.html In this patient an overlap of two conditions, dilative cardiomyopathy (DCMi) due to myocarditis and MLS, might have occurred. Patients with DCMi and hyperckemia should undergo a careful neuromuscular examination as some subclinical signs (calves-hypotrophy, areflexia) might go overlooked. We therefore suggest including the search for acanthocytes in patients with DCMi and hyperCKemia as it is a quick and cheap test that might unravel the MLS diagnosis.
    Elderly patients are a vulnerable patient population in elective spinal surgery. Older patients have more medical comorbidities and are also more sensitive to opiate medications. Despite this, spine and peripheral nerve surgery is still feasible in these patients, and an Enhanced Recovery After Surgery (ERAS) regimen can further enhance the safety profile.

    This is a before and after cohort study at a single institution on elderly patients who underwent elective spine and peripheral nerve surgery. Patients were prospectively enrolled in a novel ERAS protocol from April 2017 to December 2018. The control group was a historical cohort of patients who underwent surgery from September 2016 to December 2016. The primary outcome was self-reported opioid use at 1- and 3-months postoperatively. The secondary outcome was compliance with the ERAS protocol across several measures including patient-controlled (PCA) use, patient-reported pain scores, mobilization and ambulation status, and Foley catheter use.

    Among 5itates reduction in opiate use at 1- and 3-month intervals postoperatively in patients greater than 65 years old undergoing elective spine and peripheral nerve surgery. Early mobilization and ambulation are safe and feasible in this population.
    Middle meningeal artery (MMA) embolization can be a treatment option for selected cases of chronic subdural hematoma (CSDH) patients. However, appropriate timing of this procedure or the conditions to be considered are still not standardized.

    Between 2008 and 2018, 18 symptomatic CSDH patients underwent MMA embolization at our institution. The timing of embolization and the risk factors for recurrence of CSDH, the recurrence rate after an embolization, and the complication were thoroughly reviewed.

    Of the 18 cases, 16 patients were male. The median age at MMA embolization was 78.5 years (range, 66-98 years). The median follow-up period were eight months (range, 2-53 months). Possible risk factors for CSDH recurrence harbored by those patients were age > 74 yrs (10), brain atrophy (4), separated hematoma (3), coagulopathy (3), anticoagulant administration (3), and thrombocytopenia (1). No recurrence or complication was observed in any of the patients after the embolization.

    MMA embolization is effective and safe in preventing recurrence of CSDH with high risk of recurrence, and could be a standard treatment for such cases.
    No correlation was found between diurnal preference/sleep habits with anxiety symptoms for both BAI total score and its factors. However, women with PER3 genotype showed less interpesonal affect in depression symptomatology and more anxiety symptoms in four factors of the BAI questionnaire. Mainly because this study was based on self-report questionnaires and was limited to undergraduate students aging 18 to 30 years old. These results reinforce a role for sleep and diurnal preference in depression, and PER3 VNTR polymorphism in anxiety symptomatology, particularly in women. These results reinforce a role for sleep and diurnal preference in depression, and PER3 VNTR polymorphism in anxiety symptomatology, particularly in women. Suicidality is common in patients with migraine. Here, we performed a systematic review and estimated the prevalence of suicidal ideation (SI) and suicide attempt (SA) in patients with migraine. We searched Pubmed, Embase, Web of Science, Cochrane database library, CINAHL, and PsycINFO for relevant publications. A random-effects model was used to pool the estimates of the prevalence of SI and SA, which were also stratified by the geographical location of the research institutions from the studies included in this meta-analysis. Fifteen studies involving 2,247,648 participants with migraine were selected. Pooled prevalence estimates of SI and SA were 15.5% [95% confidence interval (CI) 10.4-21.3%] and 3.9% (95% CI 0.9-8.8%), respectively, and the prevalence of SI was higher in Asian countries (21.5%, 95%CI 16.8-26.6%) compared with non-Asian countries (11.0%, 95%CI 6.1-17.2%). Measures of heterogeneity between studies were high for all outcomes (I =89-100%), indicating that the substantial between-study heterogeneity in estimated proportions was not attributed to sampling error. The leave-one-out analysis showed that no single study significantly affected the final pooled results. This meta-analysis indicated a high prevalence of SI and SA in migraine patients. Thus, it is necessary to design targeted preventive measures for the management of migraine-related suicide. This meta-analysis indicated a high prevalence of SI and SA in migraine patients. Thus, it is necessary to design targeted preventive measures for the management of migraine-related suicide.Within the context of school-based physical education (PE), a strength and conditioning program called CrossFit Kids (CFK) has emerged as a potential intervention for positively impacting students. The purpose of this study was to evaluate through a randomized-controlled trial how academic and health-related fitness outcomes differed for middle school students (age = 12.73; 55.3 % male) who participated in a school-based CFK program (n=72) as compared to a group of students who participated in PE class (n=72). Questionnaire data were collected twice across the 9-month academic year and combined with FitnessGram and grade data. Students in both the intervention and comparison groups increased in health-related fitness outcomes (all p values less then .017), and there was a significant treatment group by time interaction on school-reported grades [F(1, 124) = 7.270, p = .008, η_P^2 = .055]. Significant gender by time interaction effects were found for the relationship between CFK or PE participation and health-related fitness outcomes, but there were no significant interaction effects by gender on academic outcomes. Because developmental outcomes are conditional and result from the coaction of many factors, the findings suggest that some elements of CFK might be beneficial to build skills yet disadvantageous to academic outcomes.Herein we report on a patient acutely admitted to the emergency room due to malaise and effort intolerance. A heart ultrasound, a cardiovascular MRI and an endomyocardial biopsy were suggestive of myocarditis. With appropriate medications the ejection fraction (EF) slowly improved but follow-up blood examinations revealed a hyperckemia. A neuromuscular examination revealed bilateral atrophy of medial gastrocnemius muscle and absent deep tendon reflexes at lower limbs . Genetic analysis revealed the presence of the hemizygous novel mutation c.757delT (p.Trp253fs) in XK gene thus confirming the diagnosis of McLeod Syndrome (MLS). https://www.selleckchem.com/products/ly2780301.html In this patient an overlap of two conditions, dilative cardiomyopathy (DCMi) due to myocarditis and MLS, might have occurred. Patients with DCMi and hyperckemia should undergo a careful neuromuscular examination as some subclinical signs (calves-hypotrophy, areflexia) might go overlooked. We therefore suggest including the search for acanthocytes in patients with DCMi and hyperCKemia as it is a quick and cheap test that might unravel the MLS diagnosis. Elderly patients are a vulnerable patient population in elective spinal surgery. Older patients have more medical comorbidities and are also more sensitive to opiate medications. Despite this, spine and peripheral nerve surgery is still feasible in these patients, and an Enhanced Recovery After Surgery (ERAS) regimen can further enhance the safety profile. This is a before and after cohort study at a single institution on elderly patients who underwent elective spine and peripheral nerve surgery. Patients were prospectively enrolled in a novel ERAS protocol from April 2017 to December 2018. The control group was a historical cohort of patients who underwent surgery from September 2016 to December 2016. The primary outcome was self-reported opioid use at 1- and 3-months postoperatively. The secondary outcome was compliance with the ERAS protocol across several measures including patient-controlled (PCA) use, patient-reported pain scores, mobilization and ambulation status, and Foley catheter use. Among 5itates reduction in opiate use at 1- and 3-month intervals postoperatively in patients greater than 65 years old undergoing elective spine and peripheral nerve surgery. Early mobilization and ambulation are safe and feasible in this population. Middle meningeal artery (MMA) embolization can be a treatment option for selected cases of chronic subdural hematoma (CSDH) patients. However, appropriate timing of this procedure or the conditions to be considered are still not standardized. Between 2008 and 2018, 18 symptomatic CSDH patients underwent MMA embolization at our institution. The timing of embolization and the risk factors for recurrence of CSDH, the recurrence rate after an embolization, and the complication were thoroughly reviewed. Of the 18 cases, 16 patients were male. The median age at MMA embolization was 78.5 years (range, 66-98 years). The median follow-up period were eight months (range, 2-53 months). Possible risk factors for CSDH recurrence harbored by those patients were age > 74 yrs (10), brain atrophy (4), separated hematoma (3), coagulopathy (3), anticoagulant administration (3), and thrombocytopenia (1). No recurrence or complication was observed in any of the patients after the embolization. MMA embolization is effective and safe in preventing recurrence of CSDH with high risk of recurrence, and could be a standard treatment for such cases.
    0 Commentaires 0 Parts 20 Vue 0 Aperçu

  • Maternal oxygenation (MO) is widely applied in obstetrics. Scholars have conducted numerous studies on maternal hyperoxygenation and have reported many theoretical and applied achievements and a number of different points of view. The main purpose of this article is to discuss the effect of maternal oxygenation on fetal circulation during normal and complicated pregnancies and to ascertain its potential side effects and research gaps in this field. In complicated pregnancies, the fetus may benefit from oxygen therapy. However, large randomized controlled trials and longitudinal studies are necessary to support the widespread application of maternal oxygenation in this context.
    In this study, chemical and microbiological contaminants were detected in fresh fruits and vegetables in peasant markets in the Department of Cundinamarca to assess food safety. At least one pesticide was detected in 63% of the samples evaluated (n = 100, including fruits and vegetables), and in 41% of these, pesticides exceeded the maximum residue limit. Within the pesticides found, 60% do not use a registry from the Instituto Colombiano Agropecuario to be applied on the crops where they were detected and are included in the toxicological categories "highly toxic" (category IB) and "moderately toxic" (category II). Heavy metals were found in 45% of the samples, with cadmium (38%) and lead (14%) being the most frequent. https://www.selleckchem.com/products/mbx-8025.html The pathogenic microorganisms Escherichia coli O157H7, Listeria monocytogenes, Salmonella, and Campylobacter sp. were detected in 4, 2, 1, and 0% of the samples, respectively. Factors concerning integrated crop management, contaminated inputs with chemicals and microorganisms, and the lack of hygiene in the postharvest stage favor the presence of pesticide residues, heavy metals, and the appearance of pathogenic microorganisms. The results suggest the need to strengthen the implementation of integrated management strategies that guarantee the safety of fresh fruits and vegetables in the country.

    Infant formula is a major nutritional component for many infants and toddlers. However, the presence of contaminants, such as toxic metals, may pose increased health risks to infants. An investigation of the total concentrations of the metals aluminum (Al), barium (Ba), and chromium (Cr) in infant formulae marketed in Lebanon was performed. Powdered dairy and nondairy infant formula samples were collected from all commercially available brands (n = 39) in the Lebanese market on two production dates (78 samples in total) and analyzed for these three metals with inductively coupled plasma mass spectrometry. All brands contained detectable concentrations of Al and Ba, Cr was detected in 95% of brands. Mean (±standard deviation) concentrations of the metals were estimated as 1.54 ± 1.43 (Al), 0.256 ± 0.593 (Ba), and 0.168 ± 0.143 (Cr) (μg/g). The concentration ranges in the powdered formula were 0.080 to 7.93 (Al), 0.038 to 5.35 (Ba), and 0.041 to 0.348 (Cr) μg/g. A significant difference in the mean concentrations of Al, Ba, and Cr for the two production dates of a single brand was observed in 92, 59, and 83% of samples, respectively. The mean concentration of Al in the soy-based formula was significantly higher than that of aluminum in milk-based and corn-based formulas (P = 0.018). Cr concentrations in the continuation special formulations were significantly higher than those in the beginner formulations (P = 0.008). Our study provides the first publicly available information on metal contamination in infant formulas in Lebanon and reveals the need for frequent monitoring and surveillance of these products intended for infant consumption.

    Antibiotic residues in consumer foods pose a threat to human health and contribute to increasing antimicrobial resistance. The study was conducted from January to July 2019 in six provinces in Vietnam. In total, 360 pork samples and 360 chicken samples were collected for analysis. The samples were first screened with an enzyme-linked immunosorbent assay test kit for residues in the beta-lactam, tetracycline, and sulfonamide groups. All positive and suspected positive samples were confirmed by liquid chromatography-tandem mass spectrometry to determine the concentration of ampicillin, amoxicillin, sulfamethazine, sulfaquinoxaline, oxytetracycline, and doxycycline residues. The final confirmed result showed that 13 (3.6%), 99 (27.5%), and 16 (4.4%) chicken samples and 13 (3.6%), 29 (8.1%), and 29 (8.1%) pork samples were positive or suspected positive with beta-lactam, tetracycline, and sulfonamide residues, respectively. The liquid chromatography-tandem mass spectrometry method detected amoxicillin (8.1 to 151.6 ng/g), ampicillin (1.9 to 7.5 ng/g), doxycycline (1.1 to 491.1 ng/g), oxytetracycline (1.1 to 12.9 ng/g), sulfaquinoxaline (1.1 to 7.3 ng/g), and sulfamethazine (1.0 to 1,556.5 ng/g) in positive or suspected positive pork and chicken samples. Tetracycline (18%) was the most frequently found residue, followed by sulfonamide (6%). The proportion of chicken samples with a residue level higher than the maximum residue limit (3%) and the level of tetracycline residue were significantly higher than pork (1%). A significantly higher proportion of samples with residue levels higher than MRL (4%) and the highest levels of tetracycline residue were observed in north Vietnam. This data can help motivate decision-making toward lowering the use of antimicrobials in livestock and antibiotic residue in livestock products.

    With the global population aging, there is demand for older adults to age in place, that is, to live and age well in their home and community with some level of independence. Community-based housing models exist and may support this process. This scoping review aimed to describe and synthesize the ways in which community-based housing models relate to older adults' aging in place and identify strengths and gaps in the literature.

    The housing models explored were villages; naturally occurring retirement communities; congregate housing and co-housing; sheltered housing; and continuing care retirement communities. This exploratory scoping review examined international peer-reviewed literature published from 2004-2019. Six databases were searched using terms related to housing models and older adults. Forty-six articles met the inclusion criteria. Descriptive numerical summary and thematic analysis were used to synthesize study characteristics and findings.

    Our analysis revealed four themes relating to aging in place in the housing models Social Relations, Health and Well-being, Sense of Self and Autonomy, and Activity Participation.
    Maternal oxygenation (MO) is widely applied in obstetrics. Scholars have conducted numerous studies on maternal hyperoxygenation and have reported many theoretical and applied achievements and a number of different points of view. The main purpose of this article is to discuss the effect of maternal oxygenation on fetal circulation during normal and complicated pregnancies and to ascertain its potential side effects and research gaps in this field. In complicated pregnancies, the fetus may benefit from oxygen therapy. However, large randomized controlled trials and longitudinal studies are necessary to support the widespread application of maternal oxygenation in this context. In this study, chemical and microbiological contaminants were detected in fresh fruits and vegetables in peasant markets in the Department of Cundinamarca to assess food safety. At least one pesticide was detected in 63% of the samples evaluated (n = 100, including fruits and vegetables), and in 41% of these, pesticides exceeded the maximum residue limit. Within the pesticides found, 60% do not use a registry from the Instituto Colombiano Agropecuario to be applied on the crops where they were detected and are included in the toxicological categories "highly toxic" (category IB) and "moderately toxic" (category II). Heavy metals were found in 45% of the samples, with cadmium (38%) and lead (14%) being the most frequent. https://www.selleckchem.com/products/mbx-8025.html The pathogenic microorganisms Escherichia coli O157H7, Listeria monocytogenes, Salmonella, and Campylobacter sp. were detected in 4, 2, 1, and 0% of the samples, respectively. Factors concerning integrated crop management, contaminated inputs with chemicals and microorganisms, and the lack of hygiene in the postharvest stage favor the presence of pesticide residues, heavy metals, and the appearance of pathogenic microorganisms. The results suggest the need to strengthen the implementation of integrated management strategies that guarantee the safety of fresh fruits and vegetables in the country. Infant formula is a major nutritional component for many infants and toddlers. However, the presence of contaminants, such as toxic metals, may pose increased health risks to infants. An investigation of the total concentrations of the metals aluminum (Al), barium (Ba), and chromium (Cr) in infant formulae marketed in Lebanon was performed. Powdered dairy and nondairy infant formula samples were collected from all commercially available brands (n = 39) in the Lebanese market on two production dates (78 samples in total) and analyzed for these three metals with inductively coupled plasma mass spectrometry. All brands contained detectable concentrations of Al and Ba, Cr was detected in 95% of brands. Mean (±standard deviation) concentrations of the metals were estimated as 1.54 ± 1.43 (Al), 0.256 ± 0.593 (Ba), and 0.168 ± 0.143 (Cr) (μg/g). The concentration ranges in the powdered formula were 0.080 to 7.93 (Al), 0.038 to 5.35 (Ba), and 0.041 to 0.348 (Cr) μg/g. A significant difference in the mean concentrations of Al, Ba, and Cr for the two production dates of a single brand was observed in 92, 59, and 83% of samples, respectively. The mean concentration of Al in the soy-based formula was significantly higher than that of aluminum in milk-based and corn-based formulas (P = 0.018). Cr concentrations in the continuation special formulations were significantly higher than those in the beginner formulations (P = 0.008). Our study provides the first publicly available information on metal contamination in infant formulas in Lebanon and reveals the need for frequent monitoring and surveillance of these products intended for infant consumption. Antibiotic residues in consumer foods pose a threat to human health and contribute to increasing antimicrobial resistance. The study was conducted from January to July 2019 in six provinces in Vietnam. In total, 360 pork samples and 360 chicken samples were collected for analysis. The samples were first screened with an enzyme-linked immunosorbent assay test kit for residues in the beta-lactam, tetracycline, and sulfonamide groups. All positive and suspected positive samples were confirmed by liquid chromatography-tandem mass spectrometry to determine the concentration of ampicillin, amoxicillin, sulfamethazine, sulfaquinoxaline, oxytetracycline, and doxycycline residues. The final confirmed result showed that 13 (3.6%), 99 (27.5%), and 16 (4.4%) chicken samples and 13 (3.6%), 29 (8.1%), and 29 (8.1%) pork samples were positive or suspected positive with beta-lactam, tetracycline, and sulfonamide residues, respectively. The liquid chromatography-tandem mass spectrometry method detected amoxicillin (8.1 to 151.6 ng/g), ampicillin (1.9 to 7.5 ng/g), doxycycline (1.1 to 491.1 ng/g), oxytetracycline (1.1 to 12.9 ng/g), sulfaquinoxaline (1.1 to 7.3 ng/g), and sulfamethazine (1.0 to 1,556.5 ng/g) in positive or suspected positive pork and chicken samples. Tetracycline (18%) was the most frequently found residue, followed by sulfonamide (6%). The proportion of chicken samples with a residue level higher than the maximum residue limit (3%) and the level of tetracycline residue were significantly higher than pork (1%). A significantly higher proportion of samples with residue levels higher than MRL (4%) and the highest levels of tetracycline residue were observed in north Vietnam. This data can help motivate decision-making toward lowering the use of antimicrobials in livestock and antibiotic residue in livestock products. With the global population aging, there is demand for older adults to age in place, that is, to live and age well in their home and community with some level of independence. Community-based housing models exist and may support this process. This scoping review aimed to describe and synthesize the ways in which community-based housing models relate to older adults' aging in place and identify strengths and gaps in the literature. The housing models explored were villages; naturally occurring retirement communities; congregate housing and co-housing; sheltered housing; and continuing care retirement communities. This exploratory scoping review examined international peer-reviewed literature published from 2004-2019. Six databases were searched using terms related to housing models and older adults. Forty-six articles met the inclusion criteria. Descriptive numerical summary and thematic analysis were used to synthesize study characteristics and findings. Our analysis revealed four themes relating to aging in place in the housing models Social Relations, Health and Well-being, Sense of Self and Autonomy, and Activity Participation.
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