-
9 Publicações
-
0 fotos
-
0 Vídeos
-
Female
-
23/03/2005
-
Seguido por 0 pessoas
Atualizações Recentes
-
In total, 168 cats (28 cases, 140 controls) were included. https://www.selleckchem.com/CDK.html Age, sex, breed, housing and total calcium were not significantly associated with UO; however, diet was. Compared with cats eating a predominantly moist food diet, cats fed a predominantly dry food diet were 15.9 times more likely to develop a UO (95% confidence interval 2.9-295;
= 0.009). There was no difference in the association between diet and UO in cats fed a mixed diet vs cats fed a predominantly moist food diet (
= 0.25). The area under the ROC curve was 72%.
Changes in diet formulation could provide a simple and economical method to reduce the risk of UO.
Changes in diet formulation could provide a simple and economical method to reduce the risk of UO.
is considered the most significant rickettsial pathogen affecting cats. The organism is transmitted by ticks of the species
in Central Europe and can cause granulocytic anaplasmosis in pets, wildlife and humans. The aims of this study were to assess the frequency of positive test results for
in cats in Germany, Austria and Switzerland, as well as to evaluate clinical and laboratory findings in cats with positive PCR results.
This study included the results of direct (PCR) and indirect detection methods (immunofluorescence antibody tests [IFAT]) requested by veterinarians in Germany, Austria and Switzerland between 2008 and 2020 from the LABOKLIN laboratory (Bad Kissingen, Germany). The veterinarians treating the PCR-positive cats were contacted by telephone to enquire about their clinical signs, laboratory findings, management and outcomes.
In total, 244/1636 cats (15%) tested positive by direct (PCR n = 27/725 [4%]) and/or indirect detection methods (IFAT n = 221/956 [23%]). In 18/26 cats with Pte prophylaxis in cats is recommended throughout the entire year.This study aimed to comprehensively evaluate whether income affects long-term health outcomes for older patients who underwent percutaneous coronary intervention (PCI) provided by a universal health coverage system. Data were from the Latter Stage Elderly Healthcare Insurance database in Fukuoka Prefecture, Japan. A total of 5625 individuals aged ≥65 years who underwent PCI in 2014-2016 were included. Cox proportional hazards models were used to assess the association between income status and the incidence of health outcomes. With a median follow-up of 1095 days, 554 acute myocardial infarction (AMI) cases, 1075 stroke cases, 1690 repeat revascularization cases, and 1094 deaths were observed. Risk of all-cause mortality decreased significantly with increasing income level in both unadjusted and adjusted Cox regression models. Patients in the low-income level had a significantly higher rate of AMI (log-rank P = 0.003), stroke (log-rank P = 0.039), and all-cause mortality (log-rank P = 0.001) compared with patients in the high-income level. Observed rates for repeat revascularization also were high in the first year after PCI. In the Japanese universal health setting, low-income patients had a comparatively higher mortality risk after PCI. Poor long-term outcomes might be attributed to patients' baseline characteristics rather than treatment processes.Anchor Institutions (AIs) provide tremendous value and benefit to the communities where they reside through initiatives, partnerships, and investments. As an academic medical center, Johns Hopkins devised to anchor its community by addressing the epidemic of violence and racial injustice through a series of webinars and a symposium entitled the "Just Us Dialogues." An analysis of all comments and policy recommendations made by panelists and attendees was performed and a series of recommendations emerged regarding how an AI should approach addressing community violence and inequities to promote community wellness. The series consisted of 4 panels "The 4th Amendment Use, Misuse, and Case for Police Reform"; "Protecting Our Youth Confronting Society's Role in the Harmonious Development of Adolescents"; "Immigration Matters Building Humanity Within a Fractured Immigration Landscape"; and "Decriminalizing Mental Illness Empathetic Approaches to Mental Health Supports." These 4 panels, symposium discussions, and the keynote address yielded 18 recommendations. The recommendations from the panels and the symposium underscore the power and leverage that AIs possess to identify and implement approaches to address community violence.Objective To determine if integrative medicine (IM) involvement can reduce acute care utilization for patients with complex medical conditions and high health care utilization. Design Prospective single-center cohort study. Interventions Twenty-nine complex high utilizer patients were treated by the University of California, Los Angeles (UCLA) East-West Extensivist IM specialty clinic with acupuncture, trigger point injections, and Traditional Chinese Medicine dietary modifications. Number of hospitalizations, hospitalization days, and emergency room visits were tracked for 6 months. Results There was a statistically significant decrease in number of hospitalizations (-31.4%, p = 0.021) and hospitalization days (-38.0%, p = 0.038) after 6 months. Subgroup analysis suggested greater improvement with more frequent visits. Conclusion IM specialty care correlates with reduced hospitalization frequency and total hospitalization days among high utilizers of care.Whether mobile phones benefit or sabotage close relationships has been a persistent subject of debate in media and communication studies. Because previous studies have demonstrated contrasting findings, further studies on this topic are required. Based on media richness theory and social penetration theory, this study investigated the direct and indirect associations between mobile communication and relationship quality (i.e., depth, support, and conflict) in romantic relationships. A survey of 1,000 university students in China revealed that relationship depth was positively predicted by mobile phone calls and negatively predicted by mobile short messages. Mobile WeChat had dialectical effects, as it reinforced relationship depth and support, but increased conflict. Regarding indirect effects, communication quality online positively mediated the effects of mobile phone calls on relationship quality and negatively mediated the effects of mobile short messages and Weibo on relationship quality. Moreover, passionate love attitudes (PLAs) and gender negatively moderated the effects of mobile phone calls on relationship depth, indicating that females and individuals who had stronger PLAs had lower relationship quality when they used mobile phone calls to interact with their romantic partners.
In total, 168 cats (28 cases, 140 controls) were included. https://www.selleckchem.com/CDK.html Age, sex, breed, housing and total calcium were not significantly associated with UO; however, diet was. Compared with cats eating a predominantly moist food diet, cats fed a predominantly dry food diet were 15.9 times more likely to develop a UO (95% confidence interval 2.9-295; = 0.009). There was no difference in the association between diet and UO in cats fed a mixed diet vs cats fed a predominantly moist food diet ( = 0.25). The area under the ROC curve was 72%. Changes in diet formulation could provide a simple and economical method to reduce the risk of UO. Changes in diet formulation could provide a simple and economical method to reduce the risk of UO. is considered the most significant rickettsial pathogen affecting cats. The organism is transmitted by ticks of the species in Central Europe and can cause granulocytic anaplasmosis in pets, wildlife and humans. The aims of this study were to assess the frequency of positive test results for in cats in Germany, Austria and Switzerland, as well as to evaluate clinical and laboratory findings in cats with positive PCR results. This study included the results of direct (PCR) and indirect detection methods (immunofluorescence antibody tests [IFAT]) requested by veterinarians in Germany, Austria and Switzerland between 2008 and 2020 from the LABOKLIN laboratory (Bad Kissingen, Germany). The veterinarians treating the PCR-positive cats were contacted by telephone to enquire about their clinical signs, laboratory findings, management and outcomes. In total, 244/1636 cats (15%) tested positive by direct (PCR n = 27/725 [4%]) and/or indirect detection methods (IFAT n = 221/956 [23%]). In 18/26 cats with Pte prophylaxis in cats is recommended throughout the entire year.This study aimed to comprehensively evaluate whether income affects long-term health outcomes for older patients who underwent percutaneous coronary intervention (PCI) provided by a universal health coverage system. Data were from the Latter Stage Elderly Healthcare Insurance database in Fukuoka Prefecture, Japan. A total of 5625 individuals aged ≥65 years who underwent PCI in 2014-2016 were included. Cox proportional hazards models were used to assess the association between income status and the incidence of health outcomes. With a median follow-up of 1095 days, 554 acute myocardial infarction (AMI) cases, 1075 stroke cases, 1690 repeat revascularization cases, and 1094 deaths were observed. Risk of all-cause mortality decreased significantly with increasing income level in both unadjusted and adjusted Cox regression models. Patients in the low-income level had a significantly higher rate of AMI (log-rank P = 0.003), stroke (log-rank P = 0.039), and all-cause mortality (log-rank P = 0.001) compared with patients in the high-income level. Observed rates for repeat revascularization also were high in the first year after PCI. In the Japanese universal health setting, low-income patients had a comparatively higher mortality risk after PCI. Poor long-term outcomes might be attributed to patients' baseline characteristics rather than treatment processes.Anchor Institutions (AIs) provide tremendous value and benefit to the communities where they reside through initiatives, partnerships, and investments. As an academic medical center, Johns Hopkins devised to anchor its community by addressing the epidemic of violence and racial injustice through a series of webinars and a symposium entitled the "Just Us Dialogues." An analysis of all comments and policy recommendations made by panelists and attendees was performed and a series of recommendations emerged regarding how an AI should approach addressing community violence and inequities to promote community wellness. The series consisted of 4 panels "The 4th Amendment Use, Misuse, and Case for Police Reform"; "Protecting Our Youth Confronting Society's Role in the Harmonious Development of Adolescents"; "Immigration Matters Building Humanity Within a Fractured Immigration Landscape"; and "Decriminalizing Mental Illness Empathetic Approaches to Mental Health Supports." These 4 panels, symposium discussions, and the keynote address yielded 18 recommendations. The recommendations from the panels and the symposium underscore the power and leverage that AIs possess to identify and implement approaches to address community violence.Objective To determine if integrative medicine (IM) involvement can reduce acute care utilization for patients with complex medical conditions and high health care utilization. Design Prospective single-center cohort study. Interventions Twenty-nine complex high utilizer patients were treated by the University of California, Los Angeles (UCLA) East-West Extensivist IM specialty clinic with acupuncture, trigger point injections, and Traditional Chinese Medicine dietary modifications. Number of hospitalizations, hospitalization days, and emergency room visits were tracked for 6 months. Results There was a statistically significant decrease in number of hospitalizations (-31.4%, p = 0.021) and hospitalization days (-38.0%, p = 0.038) after 6 months. Subgroup analysis suggested greater improvement with more frequent visits. Conclusion IM specialty care correlates with reduced hospitalization frequency and total hospitalization days among high utilizers of care.Whether mobile phones benefit or sabotage close relationships has been a persistent subject of debate in media and communication studies. Because previous studies have demonstrated contrasting findings, further studies on this topic are required. Based on media richness theory and social penetration theory, this study investigated the direct and indirect associations between mobile communication and relationship quality (i.e., depth, support, and conflict) in romantic relationships. A survey of 1,000 university students in China revealed that relationship depth was positively predicted by mobile phone calls and negatively predicted by mobile short messages. Mobile WeChat had dialectical effects, as it reinforced relationship depth and support, but increased conflict. Regarding indirect effects, communication quality online positively mediated the effects of mobile phone calls on relationship quality and negatively mediated the effects of mobile short messages and Weibo on relationship quality. Moreover, passionate love attitudes (PLAs) and gender negatively moderated the effects of mobile phone calls on relationship depth, indicating that females and individuals who had stronger PLAs had lower relationship quality when they used mobile phone calls to interact with their romantic partners.0 Comentários 0 Compartilhamentos 48 Visualizações 0 AnteriorFaça Login para curtir, compartilhar e comentar! -
The study aimed to examine health workers' perceptions of the coronavirus disease 2019 (COVID-19) vaccine in Nigeria and their willingness to receive the vaccine when it becomes available.
This multi-center cross-sectional study used non-probability convenience sampling to enroll 1,470 hospital workers aged 18 and above from 4 specialized hospitals. A structured and validated self-administered questionnaire was used for data collection. Data entry and analysis were conducted using IBM SPSS ver. 22.0.
The mean age of respondents was 40±6 years. Only 53.5% of the health workers had positive perceptions of the COVID-19 vaccine, and only slightly more than half (55.5%) were willing to receive vaccination. Predictors of willingness to receive the COVID-19 vaccine included having a positive perception of the vaccine (adjusted odds ratio [AOR], 4.55; 95% confidence interval [CI], 3.50-5.69), perceiving a risk of contracting COVID-19 (AOR, 1.50; 95% CI, 1.25-3.98), having received tertiary education (AOR, 3.50; 95% CI, 1.40-6.86), and being a clinical health worker (AOR, 1.25; 95% CI, 1.01-1.68).
Perceptions of the COVID-19 vaccine and willingness to receive the vaccine were sub-optimal among this group. Educational interventions to improve health workers' perceptions and attitudes toward the COVID-19 vaccine are needed.
Perceptions of the COVID-19 vaccine and willingness to receive the vaccine were sub-optimal among this group. Educational interventions to improve health workers' perceptions and attitudes toward the COVID-19 vaccine are needed.
Historically, the receipt of prescription opioids has differed among racial groups in the United States. Research has not sufficiently explored the contribution of individual health systems to these differences by examining within-system prescription opioid receipt according to race.
We used 2016 and 2017 Medicare claims data from a random 40% national sample of fee-for-service, Black and White beneficiaries 18 to 64 years of age who were attributed to health systems. We identified 310 racially diverse systems (defined as systems with ≥200 person-years each for Black and White patients). To test representativeness, we compared patient characteristics and opioid receipt among the patients in these 310 systems with those in the national sample. Within the 310 systems, regression models were used to explore the difference between Black and White patients in the following annual opioid measures any prescription filled, short-term receipt of opioids, long-term receipt of opioids (one or more filled opioid presthan among Black patients in 91% of the systems, and at least 15% higher in 75% of the systems.
Within individual health systems, Black and White patients received markedly different opioid doses. These system-specific findings could facilitate exploration of the causes and consequences of these differences. (Funded by the National Institute on Aging and the Agency for Healthcare Research and Quality.).
Within individual health systems, Black and White patients received markedly different opioid doses. https://www.selleckchem.com/pharmacological_epigenetics.html These system-specific findings could facilitate exploration of the causes and consequences of these differences. (Funded by the National Institute on Aging and the Agency for Healthcare Research and Quality.).
The World Health Organization recommends dolutegravir with two nucleoside reverse-transcriptase inhibitors (NRTIs) for second-line treatment of human immunodeficiency virus type 1 (HIV-1) infection. Evidence is limited for the efficacy of this regimen when NRTIs are predicted to lack activity because of drug resistance, as well as for the recommended switch of an NRTI from tenofovir to zidovudine.
In a two-by-two factorial, open-label, noninferiority trial, we randomly assigned patients for whom first-line therapy was failing (HIV-1 viral load, ≥1000 copies per milliliter) to receive dolutegravir or ritonavir-boosted darunavir and to receive tenofovir or zidovudine; all patients received lamivudine. The primary outcome was a week 48 viral load of less than 400 copies per milliliter, assessed with the Food and Drug Administration snapshot algorithm (noninferiority margin for the between-group difference in the percentage of patients with the primary outcome, 12 percentage points).
We enrolled 464 patients effective in treating patients with HIV-1 infection, including those with extensive NRTI resistance in whom no NRTIs were predicted to have activity. Tenofovir was noninferior to zidovudine as second-line therapy. (Funded by Janssen; NADIA ClinicalTrials.gov number, NCT03988452.).
Dolutegravir in combination with NRTIs was effective in treating patients with HIV-1 infection, including those with extensive NRTI resistance in whom no NRTIs were predicted to have activity. Tenofovir was noninferior to zidovudine as second-line therapy. (Funded by Janssen; NADIA ClinicalTrials.gov number, NCT03988452.).
Patients with dementia due to neurodegenerative disease can have dementia-related psychosis. The effects of the oral 5-HT
inverse agonist and antagonist pimavanserin on psychosis related to various causes of dementia are not clear.
We conducted a phase 3, double-blind, randomized, placebo-controlled discontinuation trial involving patients with psychosis related to Alzheimer's disease, Parkinson's disease dementia, dementia with Lewy bodies, frontotemporal dementia, or vascular dementia. Patients received open-label pimavanserin for 12 weeks. Those who had a reduction from baseline of at least 30% in the score on the Scale for the Assessment of Positive Symptoms-Hallucinations and Delusions (SAPS-H+D, with higher scores indicating greater psychosis) and a Clinical Global Impression-Improvement (CGI-I) score of 1 (very **** improved) or 2 (**** improved) at weeks 8 and 12 were randomly assigned in a 11 ratio to continue receiving pimavanserin or to receive placebo for up to 26 weeks. The primary end poino group. Headache, constipation, urinary tract infection, and asymptomatic QT prolongation occurred with pimavanserin.
In a trial that was stopped early for efficacy, patients with dementia-related psychosis who had a response to pimavanserin had a lower risk of relapse with continuation of the drug than with discontinuation. Longer and larger trials are required to determine the effects of pimavanserin in dementia-related psychosis. (Funded by Acadia Pharmaceuticals; HARMONY ClinicalTrials.gov number, NCT03325556.).
In a trial that was stopped early for efficacy, patients with dementia-related psychosis who had a response to pimavanserin had a lower risk of relapse with continuation of the drug than with discontinuation. Longer and larger trials are required to determine the effects of pimavanserin in dementia-related psychosis. (Funded by Acadia Pharmaceuticals; HARMONY ClinicalTrials.gov number, NCT03325556.).
The study aimed to examine health workers' perceptions of the coronavirus disease 2019 (COVID-19) vaccine in Nigeria and their willingness to receive the vaccine when it becomes available. This multi-center cross-sectional study used non-probability convenience sampling to enroll 1,470 hospital workers aged 18 and above from 4 specialized hospitals. A structured and validated self-administered questionnaire was used for data collection. Data entry and analysis were conducted using IBM SPSS ver. 22.0. The mean age of respondents was 40±6 years. Only 53.5% of the health workers had positive perceptions of the COVID-19 vaccine, and only slightly more than half (55.5%) were willing to receive vaccination. Predictors of willingness to receive the COVID-19 vaccine included having a positive perception of the vaccine (adjusted odds ratio [AOR], 4.55; 95% confidence interval [CI], 3.50-5.69), perceiving a risk of contracting COVID-19 (AOR, 1.50; 95% CI, 1.25-3.98), having received tertiary education (AOR, 3.50; 95% CI, 1.40-6.86), and being a clinical health worker (AOR, 1.25; 95% CI, 1.01-1.68). Perceptions of the COVID-19 vaccine and willingness to receive the vaccine were sub-optimal among this group. Educational interventions to improve health workers' perceptions and attitudes toward the COVID-19 vaccine are needed. Perceptions of the COVID-19 vaccine and willingness to receive the vaccine were sub-optimal among this group. Educational interventions to improve health workers' perceptions and attitudes toward the COVID-19 vaccine are needed. Historically, the receipt of prescription opioids has differed among racial groups in the United States. Research has not sufficiently explored the contribution of individual health systems to these differences by examining within-system prescription opioid receipt according to race. We used 2016 and 2017 Medicare claims data from a random 40% national sample of fee-for-service, Black and White beneficiaries 18 to 64 years of age who were attributed to health systems. We identified 310 racially diverse systems (defined as systems with ≥200 person-years each for Black and White patients). To test representativeness, we compared patient characteristics and opioid receipt among the patients in these 310 systems with those in the national sample. Within the 310 systems, regression models were used to explore the difference between Black and White patients in the following annual opioid measures any prescription filled, short-term receipt of opioids, long-term receipt of opioids (one or more filled opioid presthan among Black patients in 91% of the systems, and at least 15% higher in 75% of the systems. Within individual health systems, Black and White patients received markedly different opioid doses. These system-specific findings could facilitate exploration of the causes and consequences of these differences. (Funded by the National Institute on Aging and the Agency for Healthcare Research and Quality.). Within individual health systems, Black and White patients received markedly different opioid doses. https://www.selleckchem.com/pharmacological_epigenetics.html These system-specific findings could facilitate exploration of the causes and consequences of these differences. (Funded by the National Institute on Aging and the Agency for Healthcare Research and Quality.). The World Health Organization recommends dolutegravir with two nucleoside reverse-transcriptase inhibitors (NRTIs) for second-line treatment of human immunodeficiency virus type 1 (HIV-1) infection. Evidence is limited for the efficacy of this regimen when NRTIs are predicted to lack activity because of drug resistance, as well as for the recommended switch of an NRTI from tenofovir to zidovudine. In a two-by-two factorial, open-label, noninferiority trial, we randomly assigned patients for whom first-line therapy was failing (HIV-1 viral load, ≥1000 copies per milliliter) to receive dolutegravir or ritonavir-boosted darunavir and to receive tenofovir or zidovudine; all patients received lamivudine. The primary outcome was a week 48 viral load of less than 400 copies per milliliter, assessed with the Food and Drug Administration snapshot algorithm (noninferiority margin for the between-group difference in the percentage of patients with the primary outcome, 12 percentage points). We enrolled 464 patients effective in treating patients with HIV-1 infection, including those with extensive NRTI resistance in whom no NRTIs were predicted to have activity. Tenofovir was noninferior to zidovudine as second-line therapy. (Funded by Janssen; NADIA ClinicalTrials.gov number, NCT03988452.). Dolutegravir in combination with NRTIs was effective in treating patients with HIV-1 infection, including those with extensive NRTI resistance in whom no NRTIs were predicted to have activity. Tenofovir was noninferior to zidovudine as second-line therapy. (Funded by Janssen; NADIA ClinicalTrials.gov number, NCT03988452.). Patients with dementia due to neurodegenerative disease can have dementia-related psychosis. The effects of the oral 5-HT inverse agonist and antagonist pimavanserin on psychosis related to various causes of dementia are not clear. We conducted a phase 3, double-blind, randomized, placebo-controlled discontinuation trial involving patients with psychosis related to Alzheimer's disease, Parkinson's disease dementia, dementia with Lewy bodies, frontotemporal dementia, or vascular dementia. Patients received open-label pimavanserin for 12 weeks. Those who had a reduction from baseline of at least 30% in the score on the Scale for the Assessment of Positive Symptoms-Hallucinations and Delusions (SAPS-H+D, with higher scores indicating greater psychosis) and a Clinical Global Impression-Improvement (CGI-I) score of 1 (very much improved) or 2 (much improved) at weeks 8 and 12 were randomly assigned in a 11 ratio to continue receiving pimavanserin or to receive placebo for up to 26 weeks. The primary end poino group. Headache, constipation, urinary tract infection, and asymptomatic QT prolongation occurred with pimavanserin. In a trial that was stopped early for efficacy, patients with dementia-related psychosis who had a response to pimavanserin had a lower risk of relapse with continuation of the drug than with discontinuation. Longer and larger trials are required to determine the effects of pimavanserin in dementia-related psychosis. (Funded by Acadia Pharmaceuticals; HARMONY ClinicalTrials.gov number, NCT03325556.). In a trial that was stopped early for efficacy, patients with dementia-related psychosis who had a response to pimavanserin had a lower risk of relapse with continuation of the drug than with discontinuation. Longer and larger trials are required to determine the effects of pimavanserin in dementia-related psychosis. (Funded by Acadia Pharmaceuticals; HARMONY ClinicalTrials.gov number, NCT03325556.).0 Comentários 0 Compartilhamentos 50 Visualizações 0 Anterior -
Lignin nanomaterials have emerged as a promising alternative to fossil-based chemicals and products for some potential added-value applications, which benefits from their structural diversity and biodegradability. This review elucidates a perspective in recent research on nanolignins and their nanocomposites. It summarizes the different nanolignin preparation methods, emphasizing anti-solvent precipitation, self-assembly and interfacial crosslinking. Also described are the preparation of various nanocomposites by the chemical modification of nanolignin and compounds with inorganic materials or polymers. Additionally, advances in numerous potential high-value applications, such as use in food packaging, biomedical, chemical engineering and biorefineries, are described.Increased fluid flow shear stress (FFSS) in solitary kidney alters podocyte function in vivo. FFSS-treated cultured podocytes show upregulated AKT-GSK3β-β-catenin signaling. The present study was undertaken to confirm (i) the activation of β-catenin signaling in podocytes in vivo using unilaterally nephrectomized (UNX) TOPGAL **** with the β-galactosidase reporter gene for β-catenin activation, (ii) β-catenin translocation in FFSS-treated mouse podocytes, and (iii) β-catenin signaling using publicly available data from UNX ****. The UNX of TOPGAL **** resulted in glomerular hypertrophy and increased the mesangial matrix consistent with hemodynamic adaptation. Uninephrectomized TOPGAL **** showed an increased β-galactosidase expression at 4 weeks but not at 12 weeks, as assessed using immunofluorescence microscopy (p less then 0.001 at 4 weeks; p = 0.16 at 12 weeks) and X-gal staining (p = 0.008 at 4 weeks; p = 0.65 at 12 weeks). Immunofluorescence microscopy showed a significant increase in phospho-β-catenin (Ser552, p = 0.005) at 4 weeks but not at 12 weeks (p = 0.935) following UNX, and the levels of phospho-β-catenin (Ser675) did not change. In vitro FFSS caused a sustained increase in the nuclear translocation of phospho-β-catenin (Ser552) but not phospho-β-catenin (Ser675) in podocytes. The bioinformatic analysis of the GEO dataset, #GSE53996, also identified β-catenin as a key upstream regulator. We conclude that transcription factor β-catenin mediates FFSS-induced podocyte (glomerular) injury in solitary kidney.(1) Background Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy provide survival benefits to selected patients. We aimed to report our experience and the evolution of our peritoneal surface malignancy program. (2) Methods From June 2005 to June 2017, 399 patients who underwent cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy at the Tübingen University Hospital were analyzed from a prospectively collected database. (3) Results Peritoneal metastasis from colorectal cancer was the leading indication (group 1 28%; group 2 32%). The median PCI was 15.5 (range, 1-39) in group 1 and 11 (range, 1-39) in group 2 (p = 0.002). Regarding the completeness of cytoreduction (CC), a score of 0 was achieved in 63% vs. 69% for group 1 and 2, respectively (p = 0.010). Median overall survival rates for patients in group 1 and 2 for colon cancer, ovarian cancer, gastric cancer and appendix cancer were 34 and 25 months; 45 months and not reached; 30 and 16 months; 39 months and not reached, respectively. The occurrence of grade-III and -IV complications slightly differed between groups (14.5% vs. 15.6%). No 30-day mortality occurred. (4) Conclusions Specialized centers are able to provide low-morbidity cytoreductive surgery and hyperthermic intraperitoneal chemotherapy without mortality. Strict patient selection during the time period significantly improved CC scores.Background Despite scientific evidence on prenatal physical activity and exercise, synthesized evidence is lacking on the provision of prenatal physical activity and exercise advice and counselling by prenatal healthcare providers. The scoping review seeks to fill this gap by synthesizing available literature on the provision of prenatal physical activity and exercise advice and counselling by prenatal healthcare providers to women during antenatal visits. Methods The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) search framework for scoping reviews was applied to retrieve original research articles on the prenatal physical activity and exercise practices of healthcare providers with pregnant women, published between 2010-2020, and available in English. The search databases included Google Scholar, PubMed, Science Direct, Scopus, EMBASE, The Cumulative Index for Nursing and Allied Health Literature (CINAHL), BIOMED Central, Medline and African Journal Online. Studies that fulfill post-partum pregnancy; this requires adequate knowledge of physical activity prescriptions and recommendations, which are personalised and contextual to environment. Research is needed to examine the prenatal physical activity advice and counselling from prenatal healthcare providers on issues hindering effective delivery of the aforementioned in the context of promoting prenatal physical activity in clinical or community settings.Exotic water primroses (Ludwigia spp.) are aggressive invaders in aquatic ecosystems worldwide. To date, management of exotic Ludwigia spp. has been limited to physical and chemical control methods. Biological control provides an alternative approach for the management of invasive Ludwigia spp. https://www.selleckchem.com/products/U0126.html but little is known regarding the natural enemies of these exotic plants. Herein the biology and host range of Lysathia flavipes (Boheman), a herbivorous beetle associated with Ludwigia spp. in Argentina and Uruguay, was studied to determine its suitability as a biocontrol agent for multiple closely related target weeds in the USA. The beetle matures from egg to adult in 19.9 ± 1.4 days at 25 °C; females lived 86.3 ± 35.6 days and laid 1510.6 ± 543.4 eggs over their lifespans. No-choice development and oviposition tests were conducted using four Ludwigia species and seven native plant species. Lysathia flavipes showed little discrimination between plant species larvae aggressively fed and completed development, and the resulting females (F1 generation) oviposited viable eggs on most plant species regardless of origin.
Lignin nanomaterials have emerged as a promising alternative to fossil-based chemicals and products for some potential added-value applications, which benefits from their structural diversity and biodegradability. This review elucidates a perspective in recent research on nanolignins and their nanocomposites. It summarizes the different nanolignin preparation methods, emphasizing anti-solvent precipitation, self-assembly and interfacial crosslinking. Also described are the preparation of various nanocomposites by the chemical modification of nanolignin and compounds with inorganic materials or polymers. Additionally, advances in numerous potential high-value applications, such as use in food packaging, biomedical, chemical engineering and biorefineries, are described.Increased fluid flow shear stress (FFSS) in solitary kidney alters podocyte function in vivo. FFSS-treated cultured podocytes show upregulated AKT-GSK3β-β-catenin signaling. The present study was undertaken to confirm (i) the activation of β-catenin signaling in podocytes in vivo using unilaterally nephrectomized (UNX) TOPGAL mice with the β-galactosidase reporter gene for β-catenin activation, (ii) β-catenin translocation in FFSS-treated mouse podocytes, and (iii) β-catenin signaling using publicly available data from UNX mice. The UNX of TOPGAL mice resulted in glomerular hypertrophy and increased the mesangial matrix consistent with hemodynamic adaptation. Uninephrectomized TOPGAL mice showed an increased β-galactosidase expression at 4 weeks but not at 12 weeks, as assessed using immunofluorescence microscopy (p less then 0.001 at 4 weeks; p = 0.16 at 12 weeks) and X-gal staining (p = 0.008 at 4 weeks; p = 0.65 at 12 weeks). Immunofluorescence microscopy showed a significant increase in phospho-β-catenin (Ser552, p = 0.005) at 4 weeks but not at 12 weeks (p = 0.935) following UNX, and the levels of phospho-β-catenin (Ser675) did not change. In vitro FFSS caused a sustained increase in the nuclear translocation of phospho-β-catenin (Ser552) but not phospho-β-catenin (Ser675) in podocytes. The bioinformatic analysis of the GEO dataset, #GSE53996, also identified β-catenin as a key upstream regulator. We conclude that transcription factor β-catenin mediates FFSS-induced podocyte (glomerular) injury in solitary kidney.(1) Background Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy provide survival benefits to selected patients. We aimed to report our experience and the evolution of our peritoneal surface malignancy program. (2) Methods From June 2005 to June 2017, 399 patients who underwent cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy at the Tübingen University Hospital were analyzed from a prospectively collected database. (3) Results Peritoneal metastasis from colorectal cancer was the leading indication (group 1 28%; group 2 32%). The median PCI was 15.5 (range, 1-39) in group 1 and 11 (range, 1-39) in group 2 (p = 0.002). Regarding the completeness of cytoreduction (CC), a score of 0 was achieved in 63% vs. 69% for group 1 and 2, respectively (p = 0.010). Median overall survival rates for patients in group 1 and 2 for colon cancer, ovarian cancer, gastric cancer and appendix cancer were 34 and 25 months; 45 months and not reached; 30 and 16 months; 39 months and not reached, respectively. The occurrence of grade-III and -IV complications slightly differed between groups (14.5% vs. 15.6%). No 30-day mortality occurred. (4) Conclusions Specialized centers are able to provide low-morbidity cytoreductive surgery and hyperthermic intraperitoneal chemotherapy without mortality. Strict patient selection during the time period significantly improved CC scores.Background Despite scientific evidence on prenatal physical activity and exercise, synthesized evidence is lacking on the provision of prenatal physical activity and exercise advice and counselling by prenatal healthcare providers. The scoping review seeks to fill this gap by synthesizing available literature on the provision of prenatal physical activity and exercise advice and counselling by prenatal healthcare providers to women during antenatal visits. Methods The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) search framework for scoping reviews was applied to retrieve original research articles on the prenatal physical activity and exercise practices of healthcare providers with pregnant women, published between 2010-2020, and available in English. The search databases included Google Scholar, PubMed, Science Direct, Scopus, EMBASE, The Cumulative Index for Nursing and Allied Health Literature (CINAHL), BIOMED Central, Medline and African Journal Online. Studies that fulfill post-partum pregnancy; this requires adequate knowledge of physical activity prescriptions and recommendations, which are personalised and contextual to environment. Research is needed to examine the prenatal physical activity advice and counselling from prenatal healthcare providers on issues hindering effective delivery of the aforementioned in the context of promoting prenatal physical activity in clinical or community settings.Exotic water primroses (Ludwigia spp.) are aggressive invaders in aquatic ecosystems worldwide. To date, management of exotic Ludwigia spp. has been limited to physical and chemical control methods. Biological control provides an alternative approach for the management of invasive Ludwigia spp. https://www.selleckchem.com/products/U0126.html but little is known regarding the natural enemies of these exotic plants. Herein the biology and host range of Lysathia flavipes (Boheman), a herbivorous beetle associated with Ludwigia spp. in Argentina and Uruguay, was studied to determine its suitability as a biocontrol agent for multiple closely related target weeds in the USA. The beetle matures from egg to adult in 19.9 ± 1.4 days at 25 °C; females lived 86.3 ± 35.6 days and laid 1510.6 ± 543.4 eggs over their lifespans. No-choice development and oviposition tests were conducted using four Ludwigia species and seven native plant species. Lysathia flavipes showed little discrimination between plant species larvae aggressively fed and completed development, and the resulting females (F1 generation) oviposited viable eggs on most plant species regardless of origin.0 Comentários 0 Compartilhamentos 61 Visualizações 0 Anterior -
Overall, both the laboratory and field work results demonstrated that the multiplex PCR assay developed in this study could provide a method for SARS-CoV-2 detection as robust as the single qPCR, but faster and cost-effective, reducing by three times the number of reactions, and consequently the handling time and reagents.Despite the broad occurrence of carbohydrate-protein interactions in biology, the low binding affinities of such interactions hamper the characterization of carbohydrate binding sites in the absence of three-dimensional structural models. To allow the identification of proteins interacting with specific carbohydrate epitopes, we have developed new photoactivable oligosaccharide probes. Oligosaccharides containing the 1,2-cyclic carbamate group were attached to building blocks with a primary amino group to yield the corresponding urea derivatives. Cyclic carbamates of lactose, and 3- and 2'-fucosyl lactose, were used for the conjugation with building blocks containing photoactivable diazirine, benzophenone or aryl azido groups. The resulting oligosaccharide derivatives were tested for binding to Erythrina cristagalli lectin (ECL), Aleuria aurantia lectin (AAL) and Ulex europaeus agglutinin-I (UEA I). We found that ligands containing an aryl azido photoactivable group were successfully attached to lectins. The photoactivation reaction preserved lectin integrity, as no sign of protein degradation was visible. Mass spectrometric analysis confirmed the covalent binding of between one to three oligosaccharide probes, which matched with the expected carbohydrate-binding properties of the lectins tested. The conjugation of cyclic carbamate-derivatized oligosaccharides with photoactivable aryl azido groups thus represents a convenient approach to study protein-carbohydrate interactions.Six mono-, di-, and trivalent α-d-mannopyranosyl conjugates built on aromatic scaffolds were synthesized in excellent yields by Cu(I) catalyzed azide-alkyne cycloaddition reaction (CuAAC). These conjugates were designed to have unique, flexible tails that combine a mid-tail triazole ring, to interact with the tyrosine gate, with a terminal phenyl group armed with benzylic hydroxyl groups to avoid solubility problems as well as to provide options to connect to other supports. Biological evaluation of the prepared conjugates in hemagglutination inhibition (HAI) assay revealed that potency increases with valency and the trivalent ligand 6d (HAI = 0.005 mM) is approximately sevenfold better than the best meta-oriented monovalent analogues 2d and 4d (HAI ≈ 0.033 mM) and so may serve as a good starting point to find new lead ligands.Tick-borne encephalitis (TBE) vaccines are effective and well tolerated. However, their acceptance and use by the public in endemic areas are suboptimal. To some extent this is due to the complicated dosing schedule requiring frequent boosters at variable intervals that even change with age. Simplification of the dosing schedule has failed so far as it is debated if the persistence of TBE virus (TBEV) antibodies is the only relevant factor for protection or if immune memory plays a decisive role as well. The objective here is to present the available evidence to determine the need for boosters and their interval after a primary series of three doses of FSME-IMMUN. A systematic literature review was conducted with a focus on serology, particularly seropersistence, immune memory, effectiveness, and vaccine breakthroughs (VB) of FSME-IMMUN. While after a 3-dose primary series seropositivity persisted for more than 10 years in >90% of younger subjects, it dropped to 37.5% in those 60 years or older. In contrast, (i.e., 10 years) following the three-dose primary immunization schedule without any evidence of harm at a population level. Longer booster intervals will likely drive up vaccine uptake. There is a lack of data to base an interval recommendation beyond 10 years.Virginia opossums (Didelphis virginiana) are a common synanthrope in North America, and serve as host to many species of ectoparasites. Research on captive Virginia opossums estimated that opossums eat, on average, 5500 larval ticks (Acari Ixodidae) per week. To investigate this apparent preference exhibited by opossums for ingesting ticks, we comprehensively analyzed stomach contents of 32 Virginia opossums from central Illinois. Using a dissecting microscope, we searched the contents exhaustively for ticks and tick body parts, without sieving or pre-rinsing the stomach contents. We did not locate any ticks or tick parts in the stomach contents of Virginia opossums. We also performed a vigorous literature search for corroborating evidence of tick ingestion. Our search revealed 23 manuscripts that describe diet analyses of Virginia opossums, 19 of which were conducted on stomach or digestive tract contents and four of which were scat-based analyses. None of the studies identified ticks in their analyses of diet items. We conclude that ticks are not a preferred diet item for Virginia opossums. Considering that wildlife unconditioned to laboratory conditions may exhibit non-typical behaviors, we recommend that lab-based studies of wildlife behavior be groundtruthed with studies based in natural conditions.Access to metabolic information in vivo using magnetic resonance (MR) technologies has generally been the niche of MR spectroscopy (MRS) and spectroscopic imaging (MRSI). Metabolic fluxes can be studied using the infusion of substrates labeled with magnetic isotopes, with the use of hyperpolarization especially powerful. https://www.selleckchem.com/products/bay-k-8644.html Unfortunately, these promising methods are not yet accepted clinically, where fast, simple, and reliable measurement and diagnosis are key. Recent advances in functional MRI and chemical exchange saturation transfer (CEST) MRI allow the use of water imaging to study oxygen metabolism and tissue metabolite levels. These, together with the use of novel data analysis approaches such as machine learning for all of these metabolic MR approaches, are increasing the likelihood of their clinical translation.
For individuals with severe disability requiring spine surgery, appropriate discharge destination is a challenging and complex decision. Past studies have found associations between discharge destination and postoperative outcomes but were limited by biases in sampling characteristics. The purpose of this study was to explore whether there is an association between discharge destination and odds of worse postoperative outcomes in high-risk individuals with severe/crippling/bedbound disability who received lumbar spine surgery.
This was an observational study using the Quality Outcomes Database Spine Registry. Subjects were limited to age ≥18 years, primary lumbar spine surgery, and severe disability at baseline (Oswestry Disability Index [ODI] ≥50%). Discharge destination was dichotomized to home or healthcare institution.
Of the 13,050 patients, 11,859 patients (90.9%) were discharged home and 1191 (9.1%) patients were discharged to a healthcare institution. Individuals who were discharged to a healthcare institution were older (68.
Overall, both the laboratory and field work results demonstrated that the multiplex PCR assay developed in this study could provide a method for SARS-CoV-2 detection as robust as the single qPCR, but faster and cost-effective, reducing by three times the number of reactions, and consequently the handling time and reagents.Despite the broad occurrence of carbohydrate-protein interactions in biology, the low binding affinities of such interactions hamper the characterization of carbohydrate binding sites in the absence of three-dimensional structural models. To allow the identification of proteins interacting with specific carbohydrate epitopes, we have developed new photoactivable oligosaccharide probes. Oligosaccharides containing the 1,2-cyclic carbamate group were attached to building blocks with a primary amino group to yield the corresponding urea derivatives. Cyclic carbamates of lactose, and 3- and 2'-fucosyl lactose, were used for the conjugation with building blocks containing photoactivable diazirine, benzophenone or aryl azido groups. The resulting oligosaccharide derivatives were tested for binding to Erythrina cristagalli lectin (ECL), Aleuria aurantia lectin (AAL) and Ulex europaeus agglutinin-I (UEA I). We found that ligands containing an aryl azido photoactivable group were successfully attached to lectins. The photoactivation reaction preserved lectin integrity, as no sign of protein degradation was visible. Mass spectrometric analysis confirmed the covalent binding of between one to three oligosaccharide probes, which matched with the expected carbohydrate-binding properties of the lectins tested. The conjugation of cyclic carbamate-derivatized oligosaccharides with photoactivable aryl azido groups thus represents a convenient approach to study protein-carbohydrate interactions.Six mono-, di-, and trivalent α-d-mannopyranosyl conjugates built on aromatic scaffolds were synthesized in excellent yields by Cu(I) catalyzed azide-alkyne cycloaddition reaction (CuAAC). These conjugates were designed to have unique, flexible tails that combine a mid-tail triazole ring, to interact with the tyrosine gate, with a terminal phenyl group armed with benzylic hydroxyl groups to avoid solubility problems as well as to provide options to connect to other supports. Biological evaluation of the prepared conjugates in hemagglutination inhibition (HAI) assay revealed that potency increases with valency and the trivalent ligand 6d (HAI = 0.005 mM) is approximately sevenfold better than the best meta-oriented monovalent analogues 2d and 4d (HAI ≈ 0.033 mM) and so may serve as a good starting point to find new lead ligands.Tick-borne encephalitis (TBE) vaccines are effective and well tolerated. However, their acceptance and use by the public in endemic areas are suboptimal. To some extent this is due to the complicated dosing schedule requiring frequent boosters at variable intervals that even change with age. Simplification of the dosing schedule has failed so far as it is debated if the persistence of TBE virus (TBEV) antibodies is the only relevant factor for protection or if immune memory plays a decisive role as well. The objective here is to present the available evidence to determine the need for boosters and their interval after a primary series of three doses of FSME-IMMUN. A systematic literature review was conducted with a focus on serology, particularly seropersistence, immune memory, effectiveness, and vaccine breakthroughs (VB) of FSME-IMMUN. While after a 3-dose primary series seropositivity persisted for more than 10 years in >90% of younger subjects, it dropped to 37.5% in those 60 years or older. In contrast, (i.e., 10 years) following the three-dose primary immunization schedule without any evidence of harm at a population level. Longer booster intervals will likely drive up vaccine uptake. There is a lack of data to base an interval recommendation beyond 10 years.Virginia opossums (Didelphis virginiana) are a common synanthrope in North America, and serve as host to many species of ectoparasites. Research on captive Virginia opossums estimated that opossums eat, on average, 5500 larval ticks (Acari Ixodidae) per week. To investigate this apparent preference exhibited by opossums for ingesting ticks, we comprehensively analyzed stomach contents of 32 Virginia opossums from central Illinois. Using a dissecting microscope, we searched the contents exhaustively for ticks and tick body parts, without sieving or pre-rinsing the stomach contents. We did not locate any ticks or tick parts in the stomach contents of Virginia opossums. We also performed a vigorous literature search for corroborating evidence of tick ingestion. Our search revealed 23 manuscripts that describe diet analyses of Virginia opossums, 19 of which were conducted on stomach or digestive tract contents and four of which were scat-based analyses. None of the studies identified ticks in their analyses of diet items. We conclude that ticks are not a preferred diet item for Virginia opossums. Considering that wildlife unconditioned to laboratory conditions may exhibit non-typical behaviors, we recommend that lab-based studies of wildlife behavior be groundtruthed with studies based in natural conditions.Access to metabolic information in vivo using magnetic resonance (MR) technologies has generally been the niche of MR spectroscopy (MRS) and spectroscopic imaging (MRSI). Metabolic fluxes can be studied using the infusion of substrates labeled with magnetic isotopes, with the use of hyperpolarization especially powerful. https://www.selleckchem.com/products/bay-k-8644.html Unfortunately, these promising methods are not yet accepted clinically, where fast, simple, and reliable measurement and diagnosis are key. Recent advances in functional MRI and chemical exchange saturation transfer (CEST) MRI allow the use of water imaging to study oxygen metabolism and tissue metabolite levels. These, together with the use of novel data analysis approaches such as machine learning for all of these metabolic MR approaches, are increasing the likelihood of their clinical translation. For individuals with severe disability requiring spine surgery, appropriate discharge destination is a challenging and complex decision. Past studies have found associations between discharge destination and postoperative outcomes but were limited by biases in sampling characteristics. The purpose of this study was to explore whether there is an association between discharge destination and odds of worse postoperative outcomes in high-risk individuals with severe/crippling/bedbound disability who received lumbar spine surgery. This was an observational study using the Quality Outcomes Database Spine Registry. Subjects were limited to age ≥18 years, primary lumbar spine surgery, and severe disability at baseline (Oswestry Disability Index [ODI] ≥50%). Discharge destination was dichotomized to home or healthcare institution. Of the 13,050 patients, 11,859 patients (90.9%) were discharged home and 1191 (9.1%) patients were discharged to a healthcare institution. Individuals who were discharged to a healthcare institution were older (68.0 Comentários 0 Compartilhamentos 57 Visualizações 0 Anterior -
Although a training program could considerably contribute to reduce stress levels and its impact on performance, there is a gap between the needs of residents and the current training program. An evidence-based education program in stress reduction is urgently warranted.
Although a training program could considerably contribute to reduce stress levels and its impact on performance, there is a gap between the needs of residents and the current training program. An evidence-based education program in stress reduction is urgently warranted.Human endometrial cancer is one of the most common malignant tumors in women with an increased incidence by years. The biological function of miR-15b-3p in endometrial cancer is still unclear. Therefore, this study explores the expression and potential mechanism of miR-15b-3p in endometrial cancer, providing a novel theory basis for targeted therapy. Herein, differentially expressed miRNAs and mRNAs in endometrial cancer were determined by bioinformatics analysis. qRT-PCR measured expression of miRNAs and mRNAs. The protein expression of mRNA in cells was determined by western blot. MTT, wound healing, and Transwell assays evaluated the biological behavior of cells. Dual luciferase assay validated the targeted relationship between target miRNA and mRNA. miR-15b-3p was highly expressed in endometrial cancer, and overexpression of miR-15b-3p promoted the malignant progression of endometrial cancer cells. KLF2 was a downstream target of miR-15b-3p, and overexpression of KLF2 reversed the facilitation of miR-15b-3p on endometrial cancer cells. miR-15b-3p promoted the proliferation, migration, and invasion of endometrial cancer cells by targeting KLF2, which made miR-15b-3p a potential diagnostic factor and new molecular therapeutic target for endometrial cancer.Fibroblast growth factors (FGFs) and their receptors (FGFRs) are important for signaling to maintain cancer stem-like cells (CSCs) in esophageal squamous cell carcinoma (ESCC). However, which FGF receptor, 1, 2, 3, 4, and L1, is essential or whether FGFRs have distinct different roles in ESCC-CSCs is still in question. This study shows that FGFR2, particularly the IIIb isoform, is highly expressed in non-CSCs. Non-CSCs have an epithelial phenotype, and such cells are more differentiated in ESCC. Further, FGFR2 induces keratinocyte differentiation through AKT but not MAPK signaling and diminishes CSC populations. Conversely, knockdown of FGFR2 induces epithelial-mesenchymal transition (EMT) and enriches CSC populations in ESCC. Finally, data analysis using The Cancer Genome Atlas (TCGA) dataset shows that expression of FGFR2 significantly correlated with cancer cell differentiation in clinical ESCC samples. The present study shows that each FGFR has a distinct role and FGFR2-AKT signaling is a key driver of keratinocyte differentiation in ESCC. Activation of FGFR2-AKT signaling could be a future therapeutic option targeting CSC in ESCC.Long non-coding RNAs (lncRNAs) play a vital regulatory role in many human cancers. However, their underlying effect and molecular mechanism in chemoresistance need to be fully researched. This study found that lncRNA CYTOR expression was significantly up-regulated in colon carcinoma tissue and cells. Silencing lncRNA CYTOR in vitro facilitated L-OHP sensitivity of colon carcinoma cells and restrained epithelial-mesenchymal transition (EMT). Furthermore, lncRNA CYTOR could inhibit miR-378a-5p expression, while suppressing miR-378a-5p could attenuate the inhibition of lncRNA CYTOR silencing on L-OHP resistance and EMT. The downstream target mRNA of miR-378a-5p was further explored, and it was discovered that miR-378a-5p restrained SERPINE1 expression. Rescue assay indicated that overexpressing miR-378a-5p or silencing SERPINE1 expression counteracted the promotion of lncRNA CYTOR overexpression on L-OHP resistance and EMT of colon carcinoma cells. In vivo experiment exhibited that silencing lncRNA CYTOR repressed colon carcinoma growth, while miR-378a-5p inhibition diminished the suppression of silencing lncRNA CYTOR on colon carcinoma. These results testified that lncRNA CYTOR enhanced L-OHP drug resistance and induced EMT in colon carcinoma. It was also suggested that lncRNA CYTOR/miR-378a-5p/SERPINE1 axis was a regulatory pathway of L-OHP resistance in colon carcinoma. They could be potential therapeutic targets and prognostic biomarkers.Abbreviations ATG autophagy related; EPG ectopic PGL granules; GFP green fluorescent protein; LGG-1 LC3, GABARAP and GATE-16 family; LPLA-2 lysosomal phospholipase A2; PGL P granule abnormality protein; PLA2 phospholipase A2; SD standard deviation; SEPA-1 suppressor of ectopic P granules in autophagy mutant; SQST-1 sequestosome related.Regulators of G protein signaling (RGSs) are proteins that negatively regulate G protein signal transduction. In this study, seven putative RGSs were characterized in the nematode-trapping (NT) fungus, Arthrobotrys oligospora. Deleting Rgs genes significantly increased intracellular cAMP levels, and caused defects in mycelia growth, stress resistance, conidiation, trap formation, and nematocidal activity. In particular, the ΔAoFlbA mutant was unable to produce conidia and traps. Transcriptomic analysis showed that amino acid metabolic and biosynthetic processes were significantly enriched in the ΔAoFlbA mutant compared to WT. https://www.selleckchem.com/products/sch-527123.html Interestingly, Gas1 family genes are significantly expanded in A. oligospora and other NT fungi that produce adhesive traps, and are differentially expressed during trap formation in A. oligospora. Disruption of two Gas1 genes resulted in defective conidiation, trap formation, and pathogenicity. Our results indicate that RGSs play pleiotropic roles in regulating A. oligospora mycelial growth, development, and pathogenicity. Further, AoFlbA is a prominent member and required for conidiation and trap formation, possibly by regulating amino acid metabolism and biosynthesis. Our results provide a basis for elucidating the signaling mechanism of vegetative growth, lifestyle transition, and pathogenicity in NT fungi.According to the International Conference on Harmonisation E14 Q&As R3, concentration-QTc analysis can serve as an alternative to the by-time-point analysis or intersection-union test as the primary basis for decisions to classify the QTc risk of a drug. In a recent scientific white paper on concentration-QTc analysis, a pre-specified linear mixed effect model was suggested to study a QTc prolongation effect. The model assumes a direct time-concordant relationship (direct effect) between QTc interval and drug-concentrations. In the case of lagged drug QTc effects, also called 'hysteresis', a linear direct effect model may yield a biased QTc estimate. In this work, we estimate the bias of QTc effects via simulations when hysteresis is not accounted for in the linear mixed effect model analysis. Simulations are performed to compare different methods of identifying hysteresis when two physiologically plausible QT drug mechanisms are considered. The focus of this paper is to provide hysteresis identification methods and assess the influence of hysteresis in estimating the QT prolongation for most commonly observed QT-Concentration profiles.
Although a training program could considerably contribute to reduce stress levels and its impact on performance, there is a gap between the needs of residents and the current training program. An evidence-based education program in stress reduction is urgently warranted. Although a training program could considerably contribute to reduce stress levels and its impact on performance, there is a gap between the needs of residents and the current training program. An evidence-based education program in stress reduction is urgently warranted.Human endometrial cancer is one of the most common malignant tumors in women with an increased incidence by years. The biological function of miR-15b-3p in endometrial cancer is still unclear. Therefore, this study explores the expression and potential mechanism of miR-15b-3p in endometrial cancer, providing a novel theory basis for targeted therapy. Herein, differentially expressed miRNAs and mRNAs in endometrial cancer were determined by bioinformatics analysis. qRT-PCR measured expression of miRNAs and mRNAs. The protein expression of mRNA in cells was determined by western blot. MTT, wound healing, and Transwell assays evaluated the biological behavior of cells. Dual luciferase assay validated the targeted relationship between target miRNA and mRNA. miR-15b-3p was highly expressed in endometrial cancer, and overexpression of miR-15b-3p promoted the malignant progression of endometrial cancer cells. KLF2 was a downstream target of miR-15b-3p, and overexpression of KLF2 reversed the facilitation of miR-15b-3p on endometrial cancer cells. miR-15b-3p promoted the proliferation, migration, and invasion of endometrial cancer cells by targeting KLF2, which made miR-15b-3p a potential diagnostic factor and new molecular therapeutic target for endometrial cancer.Fibroblast growth factors (FGFs) and their receptors (FGFRs) are important for signaling to maintain cancer stem-like cells (CSCs) in esophageal squamous cell carcinoma (ESCC). However, which FGF receptor, 1, 2, 3, 4, and L1, is essential or whether FGFRs have distinct different roles in ESCC-CSCs is still in question. This study shows that FGFR2, particularly the IIIb isoform, is highly expressed in non-CSCs. Non-CSCs have an epithelial phenotype, and such cells are more differentiated in ESCC. Further, FGFR2 induces keratinocyte differentiation through AKT but not MAPK signaling and diminishes CSC populations. Conversely, knockdown of FGFR2 induces epithelial-mesenchymal transition (EMT) and enriches CSC populations in ESCC. Finally, data analysis using The Cancer Genome Atlas (TCGA) dataset shows that expression of FGFR2 significantly correlated with cancer cell differentiation in clinical ESCC samples. The present study shows that each FGFR has a distinct role and FGFR2-AKT signaling is a key driver of keratinocyte differentiation in ESCC. Activation of FGFR2-AKT signaling could be a future therapeutic option targeting CSC in ESCC.Long non-coding RNAs (lncRNAs) play a vital regulatory role in many human cancers. However, their underlying effect and molecular mechanism in chemoresistance need to be fully researched. This study found that lncRNA CYTOR expression was significantly up-regulated in colon carcinoma tissue and cells. Silencing lncRNA CYTOR in vitro facilitated L-OHP sensitivity of colon carcinoma cells and restrained epithelial-mesenchymal transition (EMT). Furthermore, lncRNA CYTOR could inhibit miR-378a-5p expression, while suppressing miR-378a-5p could attenuate the inhibition of lncRNA CYTOR silencing on L-OHP resistance and EMT. The downstream target mRNA of miR-378a-5p was further explored, and it was discovered that miR-378a-5p restrained SERPINE1 expression. Rescue assay indicated that overexpressing miR-378a-5p or silencing SERPINE1 expression counteracted the promotion of lncRNA CYTOR overexpression on L-OHP resistance and EMT of colon carcinoma cells. In vivo experiment exhibited that silencing lncRNA CYTOR repressed colon carcinoma growth, while miR-378a-5p inhibition diminished the suppression of silencing lncRNA CYTOR on colon carcinoma. These results testified that lncRNA CYTOR enhanced L-OHP drug resistance and induced EMT in colon carcinoma. It was also suggested that lncRNA CYTOR/miR-378a-5p/SERPINE1 axis was a regulatory pathway of L-OHP resistance in colon carcinoma. They could be potential therapeutic targets and prognostic biomarkers.Abbreviations ATG autophagy related; EPG ectopic PGL granules; GFP green fluorescent protein; LGG-1 LC3, GABARAP and GATE-16 family; LPLA-2 lysosomal phospholipase A2; PGL P granule abnormality protein; PLA2 phospholipase A2; SD standard deviation; SEPA-1 suppressor of ectopic P granules in autophagy mutant; SQST-1 sequestosome related.Regulators of G protein signaling (RGSs) are proteins that negatively regulate G protein signal transduction. In this study, seven putative RGSs were characterized in the nematode-trapping (NT) fungus, Arthrobotrys oligospora. Deleting Rgs genes significantly increased intracellular cAMP levels, and caused defects in mycelia growth, stress resistance, conidiation, trap formation, and nematocidal activity. In particular, the ΔAoFlbA mutant was unable to produce conidia and traps. Transcriptomic analysis showed that amino acid metabolic and biosynthetic processes were significantly enriched in the ΔAoFlbA mutant compared to WT. https://www.selleckchem.com/products/sch-527123.html Interestingly, Gas1 family genes are significantly expanded in A. oligospora and other NT fungi that produce adhesive traps, and are differentially expressed during trap formation in A. oligospora. Disruption of two Gas1 genes resulted in defective conidiation, trap formation, and pathogenicity. Our results indicate that RGSs play pleiotropic roles in regulating A. oligospora mycelial growth, development, and pathogenicity. Further, AoFlbA is a prominent member and required for conidiation and trap formation, possibly by regulating amino acid metabolism and biosynthesis. Our results provide a basis for elucidating the signaling mechanism of vegetative growth, lifestyle transition, and pathogenicity in NT fungi.According to the International Conference on Harmonisation E14 Q&As R3, concentration-QTc analysis can serve as an alternative to the by-time-point analysis or intersection-union test as the primary basis for decisions to classify the QTc risk of a drug. In a recent scientific white paper on concentration-QTc analysis, a pre-specified linear mixed effect model was suggested to study a QTc prolongation effect. The model assumes a direct time-concordant relationship (direct effect) between QTc interval and drug-concentrations. In the case of lagged drug QTc effects, also called 'hysteresis', a linear direct effect model may yield a biased QTc estimate. In this work, we estimate the bias of QTc effects via simulations when hysteresis is not accounted for in the linear mixed effect model analysis. Simulations are performed to compare different methods of identifying hysteresis when two physiologically plausible QT drug mechanisms are considered. The focus of this paper is to provide hysteresis identification methods and assess the influence of hysteresis in estimating the QT prolongation for most commonly observed QT-Concentration profiles.0 Comentários 0 Compartilhamentos 70 Visualizações 0 Anterior -
We validate the performance and optimality of our method on both synthetic and real-world data. Additionally, we demonstrate the applicability of the proposed method for two applications refocusing and stylization.
Low-intensity ultrasound can stimulate excitable cells in a noninvasive and targeted manner, but which parameters are effective has remained elusive. This question has been difficult to answer because differences in transducers and parametersfrequency in particularlead to profound differences in the stimulated tissue volumes. The objective of this study is to control for these differences and evaluate which ultrasound parameters are effective in stimulating excitable cells.
Here, we stimulated the human peripheral nervous system using a single transducer operating in a range of frequencies, and matched the stimulated volumes with an acoustic aperture.
We found that low frequencies (300 kHz) are substantially more effective in generating tactile and nociceptive responses in humans compared to high frequencies (900 kHz). The strong effect of ultrasound frequency was observed for all pressures tested, for continuous and pulsed stimuli, and for tactile and nociceptive responses.
This prominent effect may be explained by a mechanical force associated with ultrasound. The effect is not due to heating, which would be weaker at the low frequency.
This controlled study reveals that ultrasonic stimulation of excitable cells is stronger at lower frequencies, which guides the choice of transducer hardware for effective ultrasonic stimulation of the peripheral nervous system in humans.
This controlled study reveals that ultrasonic stimulation of excitable cells is stronger at lower frequencies, which guides the choice of transducer hardware for effective ultrasonic stimulation of the peripheral nervous system in humans.The arrival of COVID-19 brought about many disruptions to our world and communities. The hospital visitation restrictions were one of the more, if not most, challenging aspects of psychosocial care for patients and families. It was difficult to anticipate the emotional toll that visitation restrictions would take on patients, families, and staff. Once hospital visitation restrictions were in place, new strategies for patient/family connection and team communication had to be established. https://www.selleckchem.com/GSK-3.html The Palliative Care team at a large, urban, Midwestern academic medical center created an interprofessional Family Support Team in the spring of 2020 to address the psychosocial needs of the families of critically ill COVID-19 patients.Millions of adolescents around the world lost their loved ones due to the COVID-19 pandemic; at the same time, health protocols in many countries do not allow mourners to practice their familiar rituals around death and dying. This study explored the experience of 15 Iranian adolescents who had lost their parent(s) during the pandemic through a phenomenological approach. Two main themes including distress in a shattered life and crisis in crisis were extracted from the interviews. Findings highlight the importance of immediate and alternative ways of support for adolescents who lost their parents during the pandemic.Several important studies advancing treatment of eating disorders were published in Eating Disorders The Journal of Treatment & Prevention in 2020. This review summarizes the recent contributions to the literature on the treatment of eating disorders, including dialectical behavior therapy, yoga for positive embodiment, and treatment innovations in children and adolescents with eating disorders. Dialectical behavior therapy can be effectively used in complex eating disorder presentations, such as with comorbid substance use disorder and with suicidal behavior, and can be adapted for culturally-responsive treatments for binge eating and for guided self-help. Yoga may promote positive embodiment, which is supported by conceptual frameworks, studies evaluating yoga treatment interventions, and systematic reviews. Advances in eating disorder treatment for children and youth include the development of the Emotional Eating Scale adapted for children and adolescents, a review of primary care interventions for eating disorder treatment, and siblings' perspectives on eating disorder treatment. Research on novel methods including telementoring and innovative treatment modalities invoking feminism are promising areas of future research.Dunaliella salina (D. salina) is a green microalga known for its tendency to produce lipid and β-carotene. Fatty acid profile, lipid and β-carotene productions of the microalga D. salina cultivated under different mixotrophic conditions were assayed. Notably, in spite of a broad spectrum of substrates served, mixotrophic cultivations slightly affected the fatty acid composition, and as a result C160 and C180, C181, C182 and C183 were identified as main fatty acids. Lipid in dry weight biomass (DWB) hit a high of 24.3% at 5% of NaCL and linolenic acid in lipid reached a peak of 9.15% at 15% of NaCL in medium containing glucose and equal amounts of yeast extract and soy bean powder. One-factor-at-a-time was applied to elucidate the substrates which had noticeable impacts on β-carotene production. Glucose, meat peptone, titanium dioxide nanoparticles (TiO2 NPs), pH 7.5 and 5% NaCL were identified as key process parameters impacting β-carotene production. Following, the concentration of glucose, meat peptone and TiO2 NPs were optimized by using response surface method. The highest content of β-carotene, 25.23 mg/g DWB, was obtained in medium composed of (g/L); 22.92 glucose, 5 meat peptone and 0.002 TiO2 NPs.The present study for the first time manifests the outstanding potential of amine grafted magnetic graphene oxide (m-GO-NH2) synthesized from Typha latifolia stems for mercury (Hg (II)) and 2,4,6-trinitrophenol (TNP) removal. The adsorption performance of m-GO-NH2 was apprized by considering the impact of the contact time (0-120 min), pH (2-9), adsorbent dose (5-40 mg), and adsorbate concentration (10-50 mg/L). The maximum Hg (II) and TNP removals (∼ 100%) were obtained using 30 mg adsorbent dose in 90 and 75 min, respectively. The best performance of m-GO-NH2 was observed at pH of 7, 20 mg/L Hg (II), and pH of 2, 30 mg/L TNP. According to the Brunauer-Emmett-Teller (BET) analysis, the surface area of GO was 34.81 m2/g and the simultaneous micro and mesoporosity was observed. Regarding the thermodynamic studies, the adsorption procedure was spontaneous and endothermic for Hg (II) followed Redlich-Peterson (R-P) and Freundlich isotherm equations while it was exothermic for TNP, well fitted with Langmuir and R-P isotherms.
We validate the performance and optimality of our method on both synthetic and real-world data. Additionally, we demonstrate the applicability of the proposed method for two applications refocusing and stylization. Low-intensity ultrasound can stimulate excitable cells in a noninvasive and targeted manner, but which parameters are effective has remained elusive. This question has been difficult to answer because differences in transducers and parametersfrequency in particularlead to profound differences in the stimulated tissue volumes. The objective of this study is to control for these differences and evaluate which ultrasound parameters are effective in stimulating excitable cells. Here, we stimulated the human peripheral nervous system using a single transducer operating in a range of frequencies, and matched the stimulated volumes with an acoustic aperture. We found that low frequencies (300 kHz) are substantially more effective in generating tactile and nociceptive responses in humans compared to high frequencies (900 kHz). The strong effect of ultrasound frequency was observed for all pressures tested, for continuous and pulsed stimuli, and for tactile and nociceptive responses. This prominent effect may be explained by a mechanical force associated with ultrasound. The effect is not due to heating, which would be weaker at the low frequency. This controlled study reveals that ultrasonic stimulation of excitable cells is stronger at lower frequencies, which guides the choice of transducer hardware for effective ultrasonic stimulation of the peripheral nervous system in humans. This controlled study reveals that ultrasonic stimulation of excitable cells is stronger at lower frequencies, which guides the choice of transducer hardware for effective ultrasonic stimulation of the peripheral nervous system in humans.The arrival of COVID-19 brought about many disruptions to our world and communities. The hospital visitation restrictions were one of the more, if not most, challenging aspects of psychosocial care for patients and families. It was difficult to anticipate the emotional toll that visitation restrictions would take on patients, families, and staff. Once hospital visitation restrictions were in place, new strategies for patient/family connection and team communication had to be established. https://www.selleckchem.com/GSK-3.html The Palliative Care team at a large, urban, Midwestern academic medical center created an interprofessional Family Support Team in the spring of 2020 to address the psychosocial needs of the families of critically ill COVID-19 patients.Millions of adolescents around the world lost their loved ones due to the COVID-19 pandemic; at the same time, health protocols in many countries do not allow mourners to practice their familiar rituals around death and dying. This study explored the experience of 15 Iranian adolescents who had lost their parent(s) during the pandemic through a phenomenological approach. Two main themes including distress in a shattered life and crisis in crisis were extracted from the interviews. Findings highlight the importance of immediate and alternative ways of support for adolescents who lost their parents during the pandemic.Several important studies advancing treatment of eating disorders were published in Eating Disorders The Journal of Treatment & Prevention in 2020. This review summarizes the recent contributions to the literature on the treatment of eating disorders, including dialectical behavior therapy, yoga for positive embodiment, and treatment innovations in children and adolescents with eating disorders. Dialectical behavior therapy can be effectively used in complex eating disorder presentations, such as with comorbid substance use disorder and with suicidal behavior, and can be adapted for culturally-responsive treatments for binge eating and for guided self-help. Yoga may promote positive embodiment, which is supported by conceptual frameworks, studies evaluating yoga treatment interventions, and systematic reviews. Advances in eating disorder treatment for children and youth include the development of the Emotional Eating Scale adapted for children and adolescents, a review of primary care interventions for eating disorder treatment, and siblings' perspectives on eating disorder treatment. Research on novel methods including telementoring and innovative treatment modalities invoking feminism are promising areas of future research.Dunaliella salina (D. salina) is a green microalga known for its tendency to produce lipid and β-carotene. Fatty acid profile, lipid and β-carotene productions of the microalga D. salina cultivated under different mixotrophic conditions were assayed. Notably, in spite of a broad spectrum of substrates served, mixotrophic cultivations slightly affected the fatty acid composition, and as a result C160 and C180, C181, C182 and C183 were identified as main fatty acids. Lipid in dry weight biomass (DWB) hit a high of 24.3% at 5% of NaCL and linolenic acid in lipid reached a peak of 9.15% at 15% of NaCL in medium containing glucose and equal amounts of yeast extract and soy bean powder. One-factor-at-a-time was applied to elucidate the substrates which had noticeable impacts on β-carotene production. Glucose, meat peptone, titanium dioxide nanoparticles (TiO2 NPs), pH 7.5 and 5% NaCL were identified as key process parameters impacting β-carotene production. Following, the concentration of glucose, meat peptone and TiO2 NPs were optimized by using response surface method. The highest content of β-carotene, 25.23 mg/g DWB, was obtained in medium composed of (g/L); 22.92 glucose, 5 meat peptone and 0.002 TiO2 NPs.The present study for the first time manifests the outstanding potential of amine grafted magnetic graphene oxide (m-GO-NH2) synthesized from Typha latifolia stems for mercury (Hg (II)) and 2,4,6-trinitrophenol (TNP) removal. The adsorption performance of m-GO-NH2 was apprized by considering the impact of the contact time (0-120 min), pH (2-9), adsorbent dose (5-40 mg), and adsorbate concentration (10-50 mg/L). The maximum Hg (II) and TNP removals (∼ 100%) were obtained using 30 mg adsorbent dose in 90 and 75 min, respectively. The best performance of m-GO-NH2 was observed at pH of 7, 20 mg/L Hg (II), and pH of 2, 30 mg/L TNP. According to the Brunauer-Emmett-Teller (BET) analysis, the surface area of GO was 34.81 m2/g and the simultaneous micro and mesoporosity was observed. Regarding the thermodynamic studies, the adsorption procedure was spontaneous and endothermic for Hg (II) followed Redlich-Peterson (R-P) and Freundlich isotherm equations while it was exothermic for TNP, well fitted with Langmuir and R-P isotherms.0 Comentários 0 Compartilhamentos 52 Visualizações 0 Anterior -
Type 1 diabetes is an autoimmune disease with rising incidence in high-income countries. Genetic and environmental predisposing factors contribute to the etiology of the disease, although their interaction is not sufficiently understood to allow for preventive action. Strongest known associations with genetic variation map to classical HLA class II genes. Because of its genetic complexity, the HLA region has been under-represented in genome-wide association studies, having potentially hindered the identification of relevant associations underlying the etiology of the disease. Here, we performed a comprehensive HLA-wide genetic association analysis of type 1 diabetes including multi-allelic and rare variants. We used high-density whole-exome sequencing data of the HLA region in the large UK Biobank dataset to apply gene-based association tests with a carefully defined type 1 diabetes phenotype (97 cases and 48,700 controls). Exon-based and single-variant association tests were used to complement the analysis. We replicated the known association of type 1 diabetes with the classical HLA-DQ gene. Tailoring the analysis toward rare variants, we additionally identified the lysine methyl transferase EHMT2 as associated. Deeper insight into genetic variation associated with disease as presented and discussed in detail here can help unraveling mechanistic details of the etiology of type 1 diabetes. More specifically, we hypothesize that genetic variation in EHMT2 could impact autoimmunity in type 1 diabetes development.Genetic patterns of inter-population variation are a result of different demographic and adaptive histories, which gradually shape the frequency distribution of the variants. However, the study of clinically relevant mutations has a Eurocentric bias. The Romani, the largest transnational minority ethnic group in Europe, originated in South Asia and received extensive gene flow from West Eurasia. Most medical genetic studies have only explored founder mutations related to Mendelian disorders in this population. Here we analyze exome sequences and genome-wide array data of 89 healthy Spanish Roma individuals to study complex traits and disease. We apply a different framework and focus on variants with both increased and decreased allele frequencies, taking into account their local ancestry. We report several OMIM traits enriched for genes with deleterious variants showing increased frequencies in Roma or in non-Roma (e.g., obesity is enriched in Roma, with an associated variant linked to South Asian ancestry; wn descent, and can differ in individuals with different ancestries.
Zebrafish are a foundational model organism for studying the spatio-temporal activity of genes and their regulatory sequences. A variety of approaches are currently available for editing genes and modifying gene expression in zebrafish, including RNAi, Cre/lox, and CRISPR-Cas9. https://www.selleckchem.com/Proteasome.html However, the
operator-repressor system, an
operon component which has been adapted for use in many other species and is a valuable, flexible tool for inducible modulation of gene expression studies, has not been previously tested in zebrafish.
Here we demonstrate that the
operator-repressor system robustly decreases expression of firefly luciferase in cultured zebrafish fibroblast cells. Our work establishes the
operator-repressor system as a promising tool for the manipulation of gene expression in whole zebrafish.
Our results lay the groundwork for the development of
based reporter assays in zebrafish, and adds to the tools available for investigating dynamic gene expression in embryogenesis. We believe this work will catalyze the development of new reporter assay systems to investigate uncharacterized regulatory elements and their cell-type specific activities.
Our results lay the groundwork for the development of lac-based reporter assays in zebrafish, and adds to the tools available for investigating dynamic gene expression in embryogenesis. We believe this work will catalyze the development of new reporter assay systems to investigate uncharacterized regulatory elements and their cell-type specific activities.Platforms for "non-invasive prenatal testing" (NIPT), or also referred to as "non-invasive prenatal screening" (NIPS) have been available for over 10 years, and are the most recent tools available to obtain information about genetic condition(s) of an unborn child. The highly praised advantage of NIPT-screening is that results can provide early hints on the detection of fetal trisomies and gonosomal numerical aberrations as early as the 10th week of gestation onward, without any need for invasive procedures, such as amniocenteses or alternatives. Understandably, the public along with gynecologists and obstetricians eagerly await these early test results. Their general hope for normal (=negative) test results is also justified, as in >95% of the tested cases such an outcome is to be expected. However, pregnant women can be disappointed and confused, particularly regarding the genetic information and proposed care when the results are positive, and these emotions are also common with false-positive and false-net care.
CD39 is one of the functional surface markers for T regulatory cells, the prognostic role and immune-related effects of CD39 in luminal breast cancer (**) patients has not been evaluated yet. The aim of the current study was to explore the association between CD39 expression and clinic pathological characteristics and the prognosis in luminal ** patients.
Clinical information and RNA-sequencing (RNA-Seq) expression data were extracted from The Cancer Genome Atlas (TCGA). Patients were divided into a high or low CD39 expression group by the optimal cutoff value (4.18) identified from the receiver operating characteristic curve analysis. The relationships between CD39 expression and clinic pathological features were evaluated by the corresponding statistical tests. Survival analyses were applied to evaluate the overall survival between the high and low CD39 expression groups in luminal **. Furthermore, Gene Expression Omnibus datasets were used for external data validation. Gene set enrichment analysis (GSEA) was also performed, and CIBERSORT was used to analyze the immune cell populations.
Type 1 diabetes is an autoimmune disease with rising incidence in high-income countries. Genetic and environmental predisposing factors contribute to the etiology of the disease, although their interaction is not sufficiently understood to allow for preventive action. Strongest known associations with genetic variation map to classical HLA class II genes. Because of its genetic complexity, the HLA region has been under-represented in genome-wide association studies, having potentially hindered the identification of relevant associations underlying the etiology of the disease. Here, we performed a comprehensive HLA-wide genetic association analysis of type 1 diabetes including multi-allelic and rare variants. We used high-density whole-exome sequencing data of the HLA region in the large UK Biobank dataset to apply gene-based association tests with a carefully defined type 1 diabetes phenotype (97 cases and 48,700 controls). Exon-based and single-variant association tests were used to complement the analysis. We replicated the known association of type 1 diabetes with the classical HLA-DQ gene. Tailoring the analysis toward rare variants, we additionally identified the lysine methyl transferase EHMT2 as associated. Deeper insight into genetic variation associated with disease as presented and discussed in detail here can help unraveling mechanistic details of the etiology of type 1 diabetes. More specifically, we hypothesize that genetic variation in EHMT2 could impact autoimmunity in type 1 diabetes development.Genetic patterns of inter-population variation are a result of different demographic and adaptive histories, which gradually shape the frequency distribution of the variants. However, the study of clinically relevant mutations has a Eurocentric bias. The Romani, the largest transnational minority ethnic group in Europe, originated in South Asia and received extensive gene flow from West Eurasia. Most medical genetic studies have only explored founder mutations related to Mendelian disorders in this population. Here we analyze exome sequences and genome-wide array data of 89 healthy Spanish Roma individuals to study complex traits and disease. We apply a different framework and focus on variants with both increased and decreased allele frequencies, taking into account their local ancestry. We report several OMIM traits enriched for genes with deleterious variants showing increased frequencies in Roma or in non-Roma (e.g., obesity is enriched in Roma, with an associated variant linked to South Asian ancestry; wn descent, and can differ in individuals with different ancestries. Zebrafish are a foundational model organism for studying the spatio-temporal activity of genes and their regulatory sequences. A variety of approaches are currently available for editing genes and modifying gene expression in zebrafish, including RNAi, Cre/lox, and CRISPR-Cas9. https://www.selleckchem.com/Proteasome.html However, the operator-repressor system, an operon component which has been adapted for use in many other species and is a valuable, flexible tool for inducible modulation of gene expression studies, has not been previously tested in zebrafish. Here we demonstrate that the operator-repressor system robustly decreases expression of firefly luciferase in cultured zebrafish fibroblast cells. Our work establishes the operator-repressor system as a promising tool for the manipulation of gene expression in whole zebrafish. Our results lay the groundwork for the development of based reporter assays in zebrafish, and adds to the tools available for investigating dynamic gene expression in embryogenesis. We believe this work will catalyze the development of new reporter assay systems to investigate uncharacterized regulatory elements and their cell-type specific activities. Our results lay the groundwork for the development of lac-based reporter assays in zebrafish, and adds to the tools available for investigating dynamic gene expression in embryogenesis. We believe this work will catalyze the development of new reporter assay systems to investigate uncharacterized regulatory elements and their cell-type specific activities.Platforms for "non-invasive prenatal testing" (NIPT), or also referred to as "non-invasive prenatal screening" (NIPS) have been available for over 10 years, and are the most recent tools available to obtain information about genetic condition(s) of an unborn child. The highly praised advantage of NIPT-screening is that results can provide early hints on the detection of fetal trisomies and gonosomal numerical aberrations as early as the 10th week of gestation onward, without any need for invasive procedures, such as amniocenteses or alternatives. Understandably, the public along with gynecologists and obstetricians eagerly await these early test results. Their general hope for normal (=negative) test results is also justified, as in >95% of the tested cases such an outcome is to be expected. However, pregnant women can be disappointed and confused, particularly regarding the genetic information and proposed care when the results are positive, and these emotions are also common with false-positive and false-net care. CD39 is one of the functional surface markers for T regulatory cells, the prognostic role and immune-related effects of CD39 in luminal breast cancer (BC) patients has not been evaluated yet. The aim of the current study was to explore the association between CD39 expression and clinic pathological characteristics and the prognosis in luminal BC patients. Clinical information and RNA-sequencing (RNA-Seq) expression data were extracted from The Cancer Genome Atlas (TCGA). Patients were divided into a high or low CD39 expression group by the optimal cutoff value (4.18) identified from the receiver operating characteristic curve analysis. The relationships between CD39 expression and clinic pathological features were evaluated by the corresponding statistical tests. Survival analyses were applied to evaluate the overall survival between the high and low CD39 expression groups in luminal BC. Furthermore, Gene Expression Omnibus datasets were used for external data validation. Gene set enrichment analysis (GSEA) was also performed, and CIBERSORT was used to analyze the immune cell populations.0 Comentários 0 Compartilhamentos 50 Visualizações 0 Anterior -
The EVIDENCE (EValuatIng connecteD sENsor teChnologiEs) checklist was developed by a multidisciplinary group of content experts convened by the Digital Medicine Society, representing the clinical sciences, data management, technology development, and biostatistics. The aim of EVIDENCE is to promote high quality reporting in studies where the primary objective is an evaluation of a digital measurement product or its constituent parts. Here we use the terms digital measurement product and connected sensor technology interchangeably to refer to tools that process data captured by mobile sensors using algorithms to generate measures of behavioral and/or physiological function. EVIDENCE is applicable to 5 types of evaluations (1) proof of concept; (2) verification, (3) analytical validation, and (4) clinical validation as defined by the V3 framework; and (5) utility and usability assessments. Using EVIDENCE, those preparing, reading, or reviewing studies evaluating digital measurement products will be better equipped to distinguish necessary reporting requirements to drive high-quality research. With broad adoption, the EVIDENCE checklist will serve as a ****-needed guide to raise the bar for quality reporting in published literature evaluating digital measurements products.Towards the objectives of the UnitedStates Food and Drug Administration (FDA) generic drug science and research program, it is of vital importance in developing product-specific guidances (PSGs) with recommendations that can facilitate and guide generic product development. To generate a PSG, the assessor needs to retrieve supportive information about the drug product of interest, including from the drug labeling, which contain comprehensive information about drug products and instructions to physicians on how to use the products for treatment. Currently, although there are many drug labeling data resources, none of them including those developed by the FDA (e.g., Drugs@FDA) can cover all the FDA-approved drug products. Furthermore, these resources, housed in various locations, are often in forms that are not compatible or interoperable with each other. Therefore, there is a great demand for retrieving useful information from a large number of textual documents from different data resources to support an effective PSG development. To meet the needs, we developed a Natural Language Processing (NLP) pipeline by integrating multiple disparate publicly available data resources to extract drug product information with minimal human intervention. We provided a case study for identifying food effect information to illustrate how a machine learning model is employed to achieve accurate paragraph labeling. We showed that the pre-trained Bidirectional Encoder Representations from Transformers (BERT) model is able to outperform the traditional machine learning techniques, setting a new state-of-the-art for labelling food effect paragraphs from drug labeling and approved drug products datasets.Our initial goal was to evaluate the contributions of high 181 phosphatidylcholine and the expression level of FAE1 to the accumulation of very-long-chain fatty acids (VLCFAs), which have wide applications as industrial feedstocks. Unexpectedly, VLCFAs were not improved by increasing the proportions of 181 in fad2-1 mutant, FAD2 artificial miRNA, and FAD2 co-suppression lines. Expressing Arabidopsis FAE1 resulted in co-suppression in 90% of transgenic lines, which was effectively released when it was expressed in the rdr6-11 mutant host. When FAE1 could be highly expressed, apart from its naturally preferred product, 201, other saturated and polyunsaturated VLCFAs also accumulated in seeds. We postulated that overabundant FAE1 might cause the diversified VLCFA profile. When FAE1 was highly expressed, knocking down FAD2 increased the content of 201, suggesting that the 181 availability in the acyl-CoA pool increased from the high 181-PC via acyl editing. Concurrent decreases of side products like 221 and 200 in these lines suggest that increasing availability of the preferred substrate could suppress the side elongation reactions and reverse the effect of VLCFA product diversification due to overabundant FAE1. https://www.selleckchem.com/products/pf-05251749.html Re-analysis of FAD2 knockdown lines indicated that increasing 181 led to a decrease of 221, which also supports the above hypothesis. These results demonstrate that 181 substrate could be increased by a downregulation of FAD2 and that a balance between the levels of enzyme and substrate may be crucial for engineering-specific VLCFA products.
Anterior vertebral body tethering (AVBT) is a growth-modulation technique theorized to correct adolescent idiopathic scoliosis (AIS) without the postoperative stiffness imposed by posterior spinal fusion. However, data are limited to small series examining short-term outcomes. To assess AVBT's potential as a viable alternative to posterior spinal fusion (PSF), a comprehensive comparison is warranted. The purpose of this meta-analysis was to compare postoperative outcomes between patients with AIS undergoing PSF and AVBT. Our primary objective was to compare complication and reoperation rates at available follow-up times. Secondary objectives included comparing mid-term Scoliosis Research Society (SRS)-22 scores, and coronal and sagittal-plane Cobb angle corrections.
We performed a systematic review of outcome studies following AVBT and/or PSF procedures. The inclusion criteria included the following AVBT and/or PSF procedures; Lenke 1 or 2 curves; an age of 10 to 18 years for >90% of the patient populale a potential fusionless treatment for AIS merits excitement, clinicians should consider AVBT with caution. Future long-term randomized prospective studies are needed.
Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Point-of-Care Ultrasound (PoCUS) has been integrated into undergraduate medical education. The COVID-19 pandemic forced medical schools to evolve clinical rotations to minimize interruption through implementation of novel remote learning courses. To address the students' need for remote clinical education, we created a virtual PoCUS course for our fourth year class. We present details of the course's development, implementation, quality improvement processes, achievements, and limitations.
A virtual PoCUS course was created for 141 fourth-year medical students. The learning objectives included ultrasound physics, performing and interpreting ultrasound applications, and incorporating PoCUS into clinical decisions and procedural guidance. Students completed a 30-question pre and post-test focused on ultrasound and knowledge of clinical concepts. PoCUS educators from 10 different specialties delivered the course over 10 days using video-conferencing software. Students watched live scanning demonstrations and practiced ultrasound probe maneuvers using a cellular telephone to simulate ultrasound probe.
The EVIDENCE (EValuatIng connecteD sENsor teChnologiEs) checklist was developed by a multidisciplinary group of content experts convened by the Digital Medicine Society, representing the clinical sciences, data management, technology development, and biostatistics. The aim of EVIDENCE is to promote high quality reporting in studies where the primary objective is an evaluation of a digital measurement product or its constituent parts. Here we use the terms digital measurement product and connected sensor technology interchangeably to refer to tools that process data captured by mobile sensors using algorithms to generate measures of behavioral and/or physiological function. EVIDENCE is applicable to 5 types of evaluations (1) proof of concept; (2) verification, (3) analytical validation, and (4) clinical validation as defined by the V3 framework; and (5) utility and usability assessments. Using EVIDENCE, those preparing, reading, or reviewing studies evaluating digital measurement products will be better equipped to distinguish necessary reporting requirements to drive high-quality research. With broad adoption, the EVIDENCE checklist will serve as a much-needed guide to raise the bar for quality reporting in published literature evaluating digital measurements products.Towards the objectives of the UnitedStates Food and Drug Administration (FDA) generic drug science and research program, it is of vital importance in developing product-specific guidances (PSGs) with recommendations that can facilitate and guide generic product development. To generate a PSG, the assessor needs to retrieve supportive information about the drug product of interest, including from the drug labeling, which contain comprehensive information about drug products and instructions to physicians on how to use the products for treatment. Currently, although there are many drug labeling data resources, none of them including those developed by the FDA (e.g., Drugs@FDA) can cover all the FDA-approved drug products. Furthermore, these resources, housed in various locations, are often in forms that are not compatible or interoperable with each other. Therefore, there is a great demand for retrieving useful information from a large number of textual documents from different data resources to support an effective PSG development. To meet the needs, we developed a Natural Language Processing (NLP) pipeline by integrating multiple disparate publicly available data resources to extract drug product information with minimal human intervention. We provided a case study for identifying food effect information to illustrate how a machine learning model is employed to achieve accurate paragraph labeling. We showed that the pre-trained Bidirectional Encoder Representations from Transformers (BERT) model is able to outperform the traditional machine learning techniques, setting a new state-of-the-art for labelling food effect paragraphs from drug labeling and approved drug products datasets.Our initial goal was to evaluate the contributions of high 181 phosphatidylcholine and the expression level of FAE1 to the accumulation of very-long-chain fatty acids (VLCFAs), which have wide applications as industrial feedstocks. Unexpectedly, VLCFAs were not improved by increasing the proportions of 181 in fad2-1 mutant, FAD2 artificial miRNA, and FAD2 co-suppression lines. Expressing Arabidopsis FAE1 resulted in co-suppression in 90% of transgenic lines, which was effectively released when it was expressed in the rdr6-11 mutant host. When FAE1 could be highly expressed, apart from its naturally preferred product, 201, other saturated and polyunsaturated VLCFAs also accumulated in seeds. We postulated that overabundant FAE1 might cause the diversified VLCFA profile. When FAE1 was highly expressed, knocking down FAD2 increased the content of 201, suggesting that the 181 availability in the acyl-CoA pool increased from the high 181-PC via acyl editing. Concurrent decreases of side products like 221 and 200 in these lines suggest that increasing availability of the preferred substrate could suppress the side elongation reactions and reverse the effect of VLCFA product diversification due to overabundant FAE1. https://www.selleckchem.com/products/pf-05251749.html Re-analysis of FAD2 knockdown lines indicated that increasing 181 led to a decrease of 221, which also supports the above hypothesis. These results demonstrate that 181 substrate could be increased by a downregulation of FAD2 and that a balance between the levels of enzyme and substrate may be crucial for engineering-specific VLCFA products. Anterior vertebral body tethering (AVBT) is a growth-modulation technique theorized to correct adolescent idiopathic scoliosis (AIS) without the postoperative stiffness imposed by posterior spinal fusion. However, data are limited to small series examining short-term outcomes. To assess AVBT's potential as a viable alternative to posterior spinal fusion (PSF), a comprehensive comparison is warranted. The purpose of this meta-analysis was to compare postoperative outcomes between patients with AIS undergoing PSF and AVBT. Our primary objective was to compare complication and reoperation rates at available follow-up times. Secondary objectives included comparing mid-term Scoliosis Research Society (SRS)-22 scores, and coronal and sagittal-plane Cobb angle corrections. We performed a systematic review of outcome studies following AVBT and/or PSF procedures. The inclusion criteria included the following AVBT and/or PSF procedures; Lenke 1 or 2 curves; an age of 10 to 18 years for >90% of the patient populale a potential fusionless treatment for AIS merits excitement, clinicians should consider AVBT with caution. Future long-term randomized prospective studies are needed. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence. Point-of-Care Ultrasound (PoCUS) has been integrated into undergraduate medical education. The COVID-19 pandemic forced medical schools to evolve clinical rotations to minimize interruption through implementation of novel remote learning courses. To address the students' need for remote clinical education, we created a virtual PoCUS course for our fourth year class. We present details of the course's development, implementation, quality improvement processes, achievements, and limitations. A virtual PoCUS course was created for 141 fourth-year medical students. The learning objectives included ultrasound physics, performing and interpreting ultrasound applications, and incorporating PoCUS into clinical decisions and procedural guidance. Students completed a 30-question pre and post-test focused on ultrasound and knowledge of clinical concepts. PoCUS educators from 10 different specialties delivered the course over 10 days using video-conferencing software. Students watched live scanning demonstrations and practiced ultrasound probe maneuvers using a cellular telephone to simulate ultrasound probe.0 Comentários 0 Compartilhamentos 170 Visualizações 0 Anterior -
Pseudomonas aeruginosa is a difficult-to-treat Gram-negative bacterial pathogen causing life-threatening infections. Adaptive resistance (AR) to cationic peptide antibiotics such as polymyxin B impairs the therapeutic success. This self-protection is mediated by two component systems (TCSs) consisting of a membrane-bound histidine kinase and an intracellular response regulator (RR). As phosphorylation of the key RR aspartate residue is transient during signaling and hydrolytically unstable, the study of these systems is challenging. Here, we apply a tailored reverse polarity chemical proteomic strategy to capture this transient modification and read-out RR phosphorylation in complex proteomes using a nucleophilic probe. In-depth mechanistic insights into an ideal trapping strategy were performed with a recombinant RR demonstrating the importance of fine-tuned acidic pH values to facilitate the attack on the aspartate carbonyl C-atom and prevent unproductive hydrolysis. Analysis of Bacillus subtilis and P. aeruginosa proteomes revealed the detection of multiple annotated phosphoaspartate (pAsp) sites of known RRs in addition to many new potential pAsp sites. With this validated strategy we dissected the signaling of dynorphin A, a human peptide stress hormone, which is sensed by P. https://www.selleckchem.com/Proteasome.html aeruginosa to prepare AR. Intriguingly, our methodology identified CprR as an unprecedented RR in dynorphin A interkingdom signaling.The asymmetric total synthesis of (+)-xestoquinone and (+)-adociaquinones A and B was achieved in 6-7 steps using an easily accessible meso-cyclohexadienone derivative. The [6,6]-bicyclic decalin ****ring and the all-carbon quaternary stereocenter at C-6 were prepared via a desymmetric intramolecular Michael reaction with up to 97% ee. The naphthalene diol D-E ring was constructed through a sequence of Ti(Oi-Pr)4-promoted photoenolization/Diels-Alder, dehydration, and aromatization reactions. This asymmetric strategy provides a scalable route to prepare target molecules and their derivatives for further biological studies.Reactions catalyzed within porous inorganic and organic materials and at electrochemical interfaces commonly occur at high coverage and in condensed media, causing turnover rates to depend strongly on interfacial structure and composition, collectively referred to as "solvent effects". Transition state theory treatments define how solvation phenomena enter kinetic rate expressions, and identify two distinct types of solvent effects that originate from molecular clustering and from the solvation of such clusters by extended solvent networks. We review examples from the recent literature that investigate reactions within microporous zeolite catalysts to illustrate these concepts, and provide a critical appraisal of open questions in the field where future research can aid in developing new chemistry and catalyst design principles.Fragment-based drug discovery is an important and increasingly reliable technology for the delivery of clinical candidates. Notably, however, sp3-rich fragments are a largely untapped resource in molecular discovery, in part due to the lack of general and suitably robust chemical methods available to aid their development into higher affinity lead and drug compounds. This Perspective describes the challenges associated with developing sp3-rich fragments, and succinctly highlights recent advances in C(sp3)-H functionalisations of high potential value towards advancing fragment hits by 'growing' functionalised rings and chains from unconventional, carbon-centred vectors.Charge carrier mobility is an important figure of merit to evaluate organic semiconductor (OSC) materials. In aggregated OSCs, this quantity is determined by inter-chromophoric electronic and vibrational coupling. These key parameters sensitively depend on structural properties, including the density of defects. We have employed a new type of crystalline assembly strategy to engineer the arrangement of the OSC pentacene in a structure not realized as crystals to date. Our approach is based on metal-organic frameworks (MOFs), in which suitably substituted pentacenes act as ditopic linkers and assemble into highly ordered π-stacks with long-range order. Layer-by-layer fabrication of the MOF yields arrays of electronically coupled pentacene chains, running parallel to the substrate surface. Detailed photophysical studies reveal strong, anisotropic inter-pentacene electronic coupling, leading to efficient charge delocalization. Despite a high degree of structural order and pronounced dispersion of the 1D-bands for the static arrangement, our experimental results demonstrate hopping-like charge transport with an activation energy of 64 meV dominating the band transport over a wide range of temperatures. A thorough combined quantum mechanical and molecular dynamics investigation identifies frustrated localized rotations of the pentacene cores as the reason for the breakdown of band transport and paves the way for a crystal engineering strategy of molecular OSCs that independently varies the arrangement of the molecular cores and their vibrational degrees of freedom.Planar chiral cyclophanopillar[5]arenes with a fused oligo(oxyethylene) or polymethylene subring (MUJs), existing as an equilibrium mixture of subring-included (in) and -excluded (out) conformers, respond to hydrostatic pressure to exhibit dynamic chiroptical property changes, leading to an unprecedented pressure-driven chirality inversion and the largest ever-reported leap of anisotropy (g) factor for the MUJ with a dodecamethylene subring. The pressure susceptivity of MUJs, assessed by the change in g per unit pressure, is a critical function of the size and nature of the subring incorporated and the solvent employed. Mechanistic elucidations reveal that the in-out equilibrium, as the origin of the MUJ's chiroptical property changes, is on a delicate balance of the competitive inclusion of subrings versus solvent molecules as well as the solvation of the excluded subring. The present results further encourage our use of pressure as a unique tool for dynamically manipulating various supramolecular devices/machines.
Pseudomonas aeruginosa is a difficult-to-treat Gram-negative bacterial pathogen causing life-threatening infections. Adaptive resistance (AR) to cationic peptide antibiotics such as polymyxin B impairs the therapeutic success. This self-protection is mediated by two component systems (TCSs) consisting of a membrane-bound histidine kinase and an intracellular response regulator (RR). As phosphorylation of the key RR aspartate residue is transient during signaling and hydrolytically unstable, the study of these systems is challenging. Here, we apply a tailored reverse polarity chemical proteomic strategy to capture this transient modification and read-out RR phosphorylation in complex proteomes using a nucleophilic probe. In-depth mechanistic insights into an ideal trapping strategy were performed with a recombinant RR demonstrating the importance of fine-tuned acidic pH values to facilitate the attack on the aspartate carbonyl C-atom and prevent unproductive hydrolysis. Analysis of Bacillus subtilis and P. aeruginosa proteomes revealed the detection of multiple annotated phosphoaspartate (pAsp) sites of known RRs in addition to many new potential pAsp sites. With this validated strategy we dissected the signaling of dynorphin A, a human peptide stress hormone, which is sensed by P. https://www.selleckchem.com/Proteasome.html aeruginosa to prepare AR. Intriguingly, our methodology identified CprR as an unprecedented RR in dynorphin A interkingdom signaling.The asymmetric total synthesis of (+)-xestoquinone and (+)-adociaquinones A and B was achieved in 6-7 steps using an easily accessible meso-cyclohexadienone derivative. The [6,6]-bicyclic decalin B-C ring and the all-carbon quaternary stereocenter at C-6 were prepared via a desymmetric intramolecular Michael reaction with up to 97% ee. The naphthalene diol D-E ring was constructed through a sequence of Ti(Oi-Pr)4-promoted photoenolization/Diels-Alder, dehydration, and aromatization reactions. This asymmetric strategy provides a scalable route to prepare target molecules and their derivatives for further biological studies.Reactions catalyzed within porous inorganic and organic materials and at electrochemical interfaces commonly occur at high coverage and in condensed media, causing turnover rates to depend strongly on interfacial structure and composition, collectively referred to as "solvent effects". Transition state theory treatments define how solvation phenomena enter kinetic rate expressions, and identify two distinct types of solvent effects that originate from molecular clustering and from the solvation of such clusters by extended solvent networks. We review examples from the recent literature that investigate reactions within microporous zeolite catalysts to illustrate these concepts, and provide a critical appraisal of open questions in the field where future research can aid in developing new chemistry and catalyst design principles.Fragment-based drug discovery is an important and increasingly reliable technology for the delivery of clinical candidates. Notably, however, sp3-rich fragments are a largely untapped resource in molecular discovery, in part due to the lack of general and suitably robust chemical methods available to aid their development into higher affinity lead and drug compounds. This Perspective describes the challenges associated with developing sp3-rich fragments, and succinctly highlights recent advances in C(sp3)-H functionalisations of high potential value towards advancing fragment hits by 'growing' functionalised rings and chains from unconventional, carbon-centred vectors.Charge carrier mobility is an important figure of merit to evaluate organic semiconductor (OSC) materials. In aggregated OSCs, this quantity is determined by inter-chromophoric electronic and vibrational coupling. These key parameters sensitively depend on structural properties, including the density of defects. We have employed a new type of crystalline assembly strategy to engineer the arrangement of the OSC pentacene in a structure not realized as crystals to date. Our approach is based on metal-organic frameworks (MOFs), in which suitably substituted pentacenes act as ditopic linkers and assemble into highly ordered π-stacks with long-range order. Layer-by-layer fabrication of the MOF yields arrays of electronically coupled pentacene chains, running parallel to the substrate surface. Detailed photophysical studies reveal strong, anisotropic inter-pentacene electronic coupling, leading to efficient charge delocalization. Despite a high degree of structural order and pronounced dispersion of the 1D-bands for the static arrangement, our experimental results demonstrate hopping-like charge transport with an activation energy of 64 meV dominating the band transport over a wide range of temperatures. A thorough combined quantum mechanical and molecular dynamics investigation identifies frustrated localized rotations of the pentacene cores as the reason for the breakdown of band transport and paves the way for a crystal engineering strategy of molecular OSCs that independently varies the arrangement of the molecular cores and their vibrational degrees of freedom.Planar chiral cyclophanopillar[5]arenes with a fused oligo(oxyethylene) or polymethylene subring (MUJs), existing as an equilibrium mixture of subring-included (in) and -excluded (out) conformers, respond to hydrostatic pressure to exhibit dynamic chiroptical property changes, leading to an unprecedented pressure-driven chirality inversion and the largest ever-reported leap of anisotropy (g) factor for the MUJ with a dodecamethylene subring. The pressure susceptivity of MUJs, assessed by the change in g per unit pressure, is a critical function of the size and nature of the subring incorporated and the solvent employed. Mechanistic elucidations reveal that the in-out equilibrium, as the origin of the MUJ's chiroptical property changes, is on a delicate balance of the competitive inclusion of subrings versus solvent molecules as well as the solvation of the excluded subring. The present results further encourage our use of pressure as a unique tool for dynamically manipulating various supramolecular devices/machines.0 Comentários 0 Compartilhamentos 12 Visualizações 0 Anterior
Mais Stories