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  • A random digit dialing sample from Missouri (USA) was used to compare associations between psychosocial factors and Alzheimer's disease (AD) screening intention based on residential locale. Linear regression associations between demographics and five psychosocial constructs (dementia knowledge, perceived screening benefits, preventive health behaviors, perceived susceptibility, and self-efficacy) and screening intention were compared by residential locale. Participants (n = 932) had a mean age of 62 years (urban n = 375; suburban n = 319, rural n = 238). African Americans more often lived in urban than suburban/rural neighborhoods, and more urban than suburban/rural residents reported insufficient income. Preventative health behaviors (e.g., dentist visits) were higher in urban and suburban versus rural participants. AD screening intention did not differ by residential locale. Among urban participants, self-efficacy to get screened was associated with screening intention. Among rural participants, dementia knowledge was associated with screening intention. Perceived screening benefits and perceived susceptibility to AD were associated with screening intention regardless of locale. Unlike urban participants, rural participants demonstrated greater screening intention with greater dementia knowledge. Our findings suggest that psychosocial factors associated with AD screening intention differ depending on residential locale. Strategies to increase dementia screening may need to account for regional variations to be maximally effective.PURPOSE The purpose of this study was to evaluate the correlation between muscle strength and knee symptoms (pain, stiffness, and functional limitation) regardless of the presence of radiologic knee osteoarthritis (RKOA) in community-dwelling elderly. PATIENTS AND METHODS This cross-sectional study used data from the Namgaram-2 cohort. The Namgaram-2 cohort consisted of participants living in three rural communities. Such participants were included for studies on activity limitation due to age-related musculoskeletal disorders including knee osteoarthritis, osteoporosis, and sarcopenia. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), a health assessment tool for patients with arthritis in lower extremities, was used to assess health-related quality of life (HRQOL). Muscle strengths were measured by knee strength (by using the isokinetic dynamometer) and hand grip strength. RESULTS The WOMAC pain of Kallgren-Lawrence (K/L) grade less then 2 was correlated with age, grip strength, nutrition status, and knee extension 180 peak torque. The WOMAC pain of K/L grade ≥ 2 was correlated with age, nutrition status, and knee extension 60 peak torque. https://www.selleckchem.com/products/umi-77.html The WOMAC stiffness of K/L grade less then 2 was correlated with having a spouse, nutrition status, and knee extension 60 peak torque. The WOMAC stiffness of K/L grade ≥ 2 was correlated with knee extension 60 peak torque. The WOMAC function of K/L grade less then 2 was correlated with age, grip strength, osteoporosis, nutrition status, and knee extension 180 peak torque. The WOMAC function of K/L grade ≥ 2 was correlated with age, nutrition status, and knee extension 60 peak torque. CONCLUSION Muscle strength as measured by grip strength and knee extension was statistically significantly correlated with the WOMAC scores in patients with knee symptoms regardless of whether radiologic signs of knee osteoarthritis were observed.The post-thrombotic syndrome (PTS) is a form of chronic venous insufficiency secondary to prior deep vein thrombosis (DVT). It affects up to 50% of patients after proximal DVT. There is no effective treatment of established PTS and its management lies in its prevention after DVT. Optimal anticoagulation is key for PTS prevention. Among anticoagulants, low-molecular-weight heparins have anti-inflammatory properties, and have a particularly attractive profile. Elastic compression stockings (ECS) may be helpful for treating acute DVT symptoms but their benefits for PTS prevention are debated. Catheter-directed techniques reduce acute DVT symptoms and might reduce the risk of moderate-severe PTS in the long term in patients with ilio-femoral DVT at low risk of bleeding. Statins may decrease the risk of PTS, but current evidence is lacking. Treatment of PTS is based on the use of ECS and lifestyle measures such as leg elevation, weight loss and exercise. Venoactive medications may be helpful and research is ongoing. Interventional techniques to treat PTS should be reserved for highly selected patients with chronic iliac obstruction or greater saphenous vein reflux, but have not yet been assessed by robust clinical trials.Magnetic nanofibers are of great interest in basic research, as well as for possible applications in spintronics and neuromorphic computing. Here we report on the preparation of magnetic nanofiber mats by electrospinning polyacrylonitrile (PAN)/nanoparticle solutions, creating a network of arbitrarily oriented nanofibers with a high aspect ratio. Since PAN is a typical precursor for carbon, the magnetic nanofiber mats were stabilized and carbonized after electrospinning. The magnetic properties of nanofiber mats containing magnetite or nickel ferrite nanoparticles were found to depend on the nanoparticle diameters and the potential after-treatment, as compared with raw nanofiber mats. Micromagnetic simulations underlined the different properties of both magnetic materials. Atomic force microscopy and scanning electron microscopy images revealed nearly unchanged morphologies after stabilization without mechanical fixation, which is in strong contrast to pure PAN nanofiber mats. While carbonization at 500 °C left the morphology unaltered, as compared with the stabilized samples, stronger connections between adjacent fibers were formed during carbonization at 800 °C, which may be supportive of magnetic data transmission.Lactobacillus fermentum UCO-979C (Lf979C) beneficially modulates the cytokine response of gastric epithelial cells and macrophages after Helicobacter pylori infection in vitro. Nevertheless, no in vivo studies were performed with this strain to confirm its beneficial immunomodulatory effects. This work evaluated whether Lf979C improves protection against H. pylori infection in **** by modulating the innate immune response. In addition, we evaluated whether its exopolysaccharide (EPS) was involved in its beneficial effects. Lf979C significantly reduced TNF-α, IL-8, and MCP-1 and augmented IFN-γ and IL-10 in the gastric mucosa of H. pylori-infected ****. The differential cytokine profile induced by Lf979C in H. pylori-infected **** correlated with an improved reduction in the pathogen gastric colonization and protection against inflammatory damage. The purified EPS of Lf979C reduced IL-8 and enhanced IL-10 levels in the gastric mucosa of infected ****, while no effect was observed for IFN-γ. This work demonstrates for the first time the in vivo ability of Lf979C to increase resistance against H.
    A random digit dialing sample from Missouri (USA) was used to compare associations between psychosocial factors and Alzheimer's disease (AD) screening intention based on residential locale. Linear regression associations between demographics and five psychosocial constructs (dementia knowledge, perceived screening benefits, preventive health behaviors, perceived susceptibility, and self-efficacy) and screening intention were compared by residential locale. Participants (n = 932) had a mean age of 62 years (urban n = 375; suburban n = 319, rural n = 238). African Americans more often lived in urban than suburban/rural neighborhoods, and more urban than suburban/rural residents reported insufficient income. Preventative health behaviors (e.g., dentist visits) were higher in urban and suburban versus rural participants. AD screening intention did not differ by residential locale. Among urban participants, self-efficacy to get screened was associated with screening intention. Among rural participants, dementia knowledge was associated with screening intention. Perceived screening benefits and perceived susceptibility to AD were associated with screening intention regardless of locale. Unlike urban participants, rural participants demonstrated greater screening intention with greater dementia knowledge. Our findings suggest that psychosocial factors associated with AD screening intention differ depending on residential locale. Strategies to increase dementia screening may need to account for regional variations to be maximally effective.PURPOSE The purpose of this study was to evaluate the correlation between muscle strength and knee symptoms (pain, stiffness, and functional limitation) regardless of the presence of radiologic knee osteoarthritis (RKOA) in community-dwelling elderly. PATIENTS AND METHODS This cross-sectional study used data from the Namgaram-2 cohort. The Namgaram-2 cohort consisted of participants living in three rural communities. Such participants were included for studies on activity limitation due to age-related musculoskeletal disorders including knee osteoarthritis, osteoporosis, and sarcopenia. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), a health assessment tool for patients with arthritis in lower extremities, was used to assess health-related quality of life (HRQOL). Muscle strengths were measured by knee strength (by using the isokinetic dynamometer) and hand grip strength. RESULTS The WOMAC pain of Kallgren-Lawrence (K/L) grade less then 2 was correlated with age, grip strength, nutrition status, and knee extension 180 peak torque. The WOMAC pain of K/L grade ≥ 2 was correlated with age, nutrition status, and knee extension 60 peak torque. https://www.selleckchem.com/products/umi-77.html The WOMAC stiffness of K/L grade less then 2 was correlated with having a spouse, nutrition status, and knee extension 60 peak torque. The WOMAC stiffness of K/L grade ≥ 2 was correlated with knee extension 60 peak torque. The WOMAC function of K/L grade less then 2 was correlated with age, grip strength, osteoporosis, nutrition status, and knee extension 180 peak torque. The WOMAC function of K/L grade ≥ 2 was correlated with age, nutrition status, and knee extension 60 peak torque. CONCLUSION Muscle strength as measured by grip strength and knee extension was statistically significantly correlated with the WOMAC scores in patients with knee symptoms regardless of whether radiologic signs of knee osteoarthritis were observed.The post-thrombotic syndrome (PTS) is a form of chronic venous insufficiency secondary to prior deep vein thrombosis (DVT). It affects up to 50% of patients after proximal DVT. There is no effective treatment of established PTS and its management lies in its prevention after DVT. Optimal anticoagulation is key for PTS prevention. Among anticoagulants, low-molecular-weight heparins have anti-inflammatory properties, and have a particularly attractive profile. Elastic compression stockings (ECS) may be helpful for treating acute DVT symptoms but their benefits for PTS prevention are debated. Catheter-directed techniques reduce acute DVT symptoms and might reduce the risk of moderate-severe PTS in the long term in patients with ilio-femoral DVT at low risk of bleeding. Statins may decrease the risk of PTS, but current evidence is lacking. Treatment of PTS is based on the use of ECS and lifestyle measures such as leg elevation, weight loss and exercise. Venoactive medications may be helpful and research is ongoing. Interventional techniques to treat PTS should be reserved for highly selected patients with chronic iliac obstruction or greater saphenous vein reflux, but have not yet been assessed by robust clinical trials.Magnetic nanofibers are of great interest in basic research, as well as for possible applications in spintronics and neuromorphic computing. Here we report on the preparation of magnetic nanofiber mats by electrospinning polyacrylonitrile (PAN)/nanoparticle solutions, creating a network of arbitrarily oriented nanofibers with a high aspect ratio. Since PAN is a typical precursor for carbon, the magnetic nanofiber mats were stabilized and carbonized after electrospinning. The magnetic properties of nanofiber mats containing magnetite or nickel ferrite nanoparticles were found to depend on the nanoparticle diameters and the potential after-treatment, as compared with raw nanofiber mats. Micromagnetic simulations underlined the different properties of both magnetic materials. Atomic force microscopy and scanning electron microscopy images revealed nearly unchanged morphologies after stabilization without mechanical fixation, which is in strong contrast to pure PAN nanofiber mats. While carbonization at 500 °C left the morphology unaltered, as compared with the stabilized samples, stronger connections between adjacent fibers were formed during carbonization at 800 °C, which may be supportive of magnetic data transmission.Lactobacillus fermentum UCO-979C (Lf979C) beneficially modulates the cytokine response of gastric epithelial cells and macrophages after Helicobacter pylori infection in vitro. Nevertheless, no in vivo studies were performed with this strain to confirm its beneficial immunomodulatory effects. This work evaluated whether Lf979C improves protection against H. pylori infection in mice by modulating the innate immune response. In addition, we evaluated whether its exopolysaccharide (EPS) was involved in its beneficial effects. Lf979C significantly reduced TNF-α, IL-8, and MCP-1 and augmented IFN-γ and IL-10 in the gastric mucosa of H. pylori-infected mice. The differential cytokine profile induced by Lf979C in H. pylori-infected mice correlated with an improved reduction in the pathogen gastric colonization and protection against inflammatory damage. The purified EPS of Lf979C reduced IL-8 and enhanced IL-10 levels in the gastric mucosa of infected mice, while no effect was observed for IFN-γ. This work demonstrates for the first time the in vivo ability of Lf979C to increase resistance against H.
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  • Non-modified (ZnO) and modified (Fe2O3@ZnO and CuO@ZnO) structured films are deposited via aerosol assisted chemical vapor deposition. The surface modification of ZnO with iron or copper oxides is achieved in a second aerosol assisted chemical vapor deposition step and the characterization of morphology, structure, and surface of these new structured films is discussed. X-ray photoelectron spectrometry and X-ray diffraction corroborate the formation of ZnO, Fe2O3, and CuO and the electron microscopy images show the morphological and crystalline characteristics of these structured films. Static water contact angle measurements for these structured films indicate hydrophobic behavior with the modified structures showing higher contact angles compared to the non-modified films. Overall, results show that the modification of ZnO with iron or copper oxides enhances the hydrophobic behavior of the surface, increasing the contact angle of the water drops at the non-modified ZnO structures from 122 to 135 and 145 for Fe2O3@ZnO and CuO@ZnO, respectively. https://www.selleckchem.com/products/corn-oil.html This is attributed to the different surface properties of the films including the morphology and chemical composition.Vitamin C (L-ascorbic acid, AA) is an essential cellular antioxidant and cofactor for several α-ketoglutarate-dependent dioxygenases. As an antioxidant, AA interacts with vitamin E to control oxidative stress. While several reports suggest an interaction of AA with folate (vitamin B9) in animals and humans, little is known about the nature of the interaction and the underlying molecular mechanisms at the cellular level. We used an untargeted metabolomics approach to study the impact of AA on the metabolome of C2C12 myoblast cells. Compared to untreated cells, treatment of C2C12 cells with AA at 100 µM resulted in enhanced concentrations of folic acid (2.5-fold) and 5-methyl-tetrahydrofolate (5-methyl-THF, 10-fold increase) whereas the relative concentrations of 10-formyl-tetrahydrofolate decreased by >90% upon AA pretreatment, indicative of increased utilization for the biosynthesis of active THF metabolites. The impact of AA on the folate-mediated one-carbon cycle further manifested itself as an increase in the levels of methionine, whose formation from homocysteine is 5-methyl-THF dependent, and an increase in thymidine, whose formation from deoxyuridine monophosphate (dUMP) is dependent on 5,10-methylene-THF. These findings shed new light on the interaction of AA with the folate-mediated one-carbon cycle and partially explain clinical findings that AA supplementation enhances erythrocyte folate status and that it may decrease serum levels of homocysteine, which is considered as a biomarker of cardiovascular disease risk.Cerebral blood flow (CBF) decreases across the lifespan, and chronic conditions such as dementia and stroke accelerate this decline. Impaired CBF results in reduced delivery of oxygen and nutrients, which can damage the brain over time. Thus, there is a need to identify lifestyle interventions, including diet and exercise, to maintain CBF with aging and in the presence of chronic disease. In the present study, we used transcranial Doppler ultrasound to record middle cerebral artery velocity (MCAv), a surrogate measure of CBF, during moderate-intensity exercise in sedentary, cognitively normal older adults (n = 90). A multiple linear regression model (F(4, 85) = 3.21, p = 0.02) showed that self-reported omega-3 supplement use significantly moderated the association between age and mean exercising MCAv in these individuals (p = 0.01). Older age was associated with lower exercising MCAv in the group not taking omega-3 supplements, while exercising MCAv showed no decline with increasing age in the group who reported omega-3 supplement use. These findings suggest omega-3 supplementation may have an important role in the preservation of CBF with aging.A composite nanofibrous layer containing collagen and hydroxyapatite was deposited on selected surface areas of titanium acetabular cups. The layer was deposited on the irregular surface of these 3D objects using a specially developed electrospinning system designed to ensure the stability of the spinning process and to produce a layer approximately 100 micrometers thick with an adequate thickness uniformity. It was verified that the layer had the intended nanostructured morphology throughout its entire thickness and that the prepared layer sufficiently adhered to the smooth surface of the model titanium implants even after all the post-deposition sterilization and stabilization treatments were performed. The resulting layers had an average thickness of (110 ± 30) micrometers and an average fiber diameter of (170 ± 49) nanometers. They were produced using a relatively simple and cost-effective technology and yet they were verifiably biocompatible and structurally stable. Collagen- and hydroxyapatite-based composite nanostructured surface modifications represent promising surface treatment options for metal implants.The aim of the study was to investigate the changes in bone geometry, histological structure, and selected mechanical characteristics in young male and female Japanese quails supplemented with Saccharomyces cerevisiae. Quails were fed a basal diet containing no yeast or a basal diet supplemented with 1.5% (15 g per 1 kg of diet) of inactive S. cerevisiae, for a period of 42 days. S. cerevisiae inclusion had no effect on bone weight, length, and density, diaphysis geometry (cross-sectional area, wall thickness, moment of inertia) or on the mechanical strength (yield load, ultimate load, stiffness, Young's modulus, yield stress, ultimate stress). Yeast supplementation improved the morphology of the articular cartilage both in male and female quails, as the total thickness of the articular cartilage was significantly increased. In trabecular bone, an increase in real bone volume and trabecular thickness was observed in females supplemented with S. cerevisiae, while in males the increase in trabecular number was accompanied by a reduction in trabecular thickness. The results of the present study demonstrate that S. cerevisiae, through a sex-dependent action on the gut-bone axis, improved the structure of articular cartilage and microarchitecture of trabecular bone. The positive effects of S. cerevisiae supplementation were more evident in female quails.
    Non-modified (ZnO) and modified (Fe2O3@ZnO and CuO@ZnO) structured films are deposited via aerosol assisted chemical vapor deposition. The surface modification of ZnO with iron or copper oxides is achieved in a second aerosol assisted chemical vapor deposition step and the characterization of morphology, structure, and surface of these new structured films is discussed. X-ray photoelectron spectrometry and X-ray diffraction corroborate the formation of ZnO, Fe2O3, and CuO and the electron microscopy images show the morphological and crystalline characteristics of these structured films. Static water contact angle measurements for these structured films indicate hydrophobic behavior with the modified structures showing higher contact angles compared to the non-modified films. Overall, results show that the modification of ZnO with iron or copper oxides enhances the hydrophobic behavior of the surface, increasing the contact angle of the water drops at the non-modified ZnO structures from 122 to 135 and 145 for Fe2O3@ZnO and CuO@ZnO, respectively. https://www.selleckchem.com/products/corn-oil.html This is attributed to the different surface properties of the films including the morphology and chemical composition.Vitamin C (L-ascorbic acid, AA) is an essential cellular antioxidant and cofactor for several α-ketoglutarate-dependent dioxygenases. As an antioxidant, AA interacts with vitamin E to control oxidative stress. While several reports suggest an interaction of AA with folate (vitamin B9) in animals and humans, little is known about the nature of the interaction and the underlying molecular mechanisms at the cellular level. We used an untargeted metabolomics approach to study the impact of AA on the metabolome of C2C12 myoblast cells. Compared to untreated cells, treatment of C2C12 cells with AA at 100 µM resulted in enhanced concentrations of folic acid (2.5-fold) and 5-methyl-tetrahydrofolate (5-methyl-THF, 10-fold increase) whereas the relative concentrations of 10-formyl-tetrahydrofolate decreased by >90% upon AA pretreatment, indicative of increased utilization for the biosynthesis of active THF metabolites. The impact of AA on the folate-mediated one-carbon cycle further manifested itself as an increase in the levels of methionine, whose formation from homocysteine is 5-methyl-THF dependent, and an increase in thymidine, whose formation from deoxyuridine monophosphate (dUMP) is dependent on 5,10-methylene-THF. These findings shed new light on the interaction of AA with the folate-mediated one-carbon cycle and partially explain clinical findings that AA supplementation enhances erythrocyte folate status and that it may decrease serum levels of homocysteine, which is considered as a biomarker of cardiovascular disease risk.Cerebral blood flow (CBF) decreases across the lifespan, and chronic conditions such as dementia and stroke accelerate this decline. Impaired CBF results in reduced delivery of oxygen and nutrients, which can damage the brain over time. Thus, there is a need to identify lifestyle interventions, including diet and exercise, to maintain CBF with aging and in the presence of chronic disease. In the present study, we used transcranial Doppler ultrasound to record middle cerebral artery velocity (MCAv), a surrogate measure of CBF, during moderate-intensity exercise in sedentary, cognitively normal older adults (n = 90). A multiple linear regression model (F(4, 85) = 3.21, p = 0.02) showed that self-reported omega-3 supplement use significantly moderated the association between age and mean exercising MCAv in these individuals (p = 0.01). Older age was associated with lower exercising MCAv in the group not taking omega-3 supplements, while exercising MCAv showed no decline with increasing age in the group who reported omega-3 supplement use. These findings suggest omega-3 supplementation may have an important role in the preservation of CBF with aging.A composite nanofibrous layer containing collagen and hydroxyapatite was deposited on selected surface areas of titanium acetabular cups. The layer was deposited on the irregular surface of these 3D objects using a specially developed electrospinning system designed to ensure the stability of the spinning process and to produce a layer approximately 100 micrometers thick with an adequate thickness uniformity. It was verified that the layer had the intended nanostructured morphology throughout its entire thickness and that the prepared layer sufficiently adhered to the smooth surface of the model titanium implants even after all the post-deposition sterilization and stabilization treatments were performed. The resulting layers had an average thickness of (110 ± 30) micrometers and an average fiber diameter of (170 ± 49) nanometers. They were produced using a relatively simple and cost-effective technology and yet they were verifiably biocompatible and structurally stable. Collagen- and hydroxyapatite-based composite nanostructured surface modifications represent promising surface treatment options for metal implants.The aim of the study was to investigate the changes in bone geometry, histological structure, and selected mechanical characteristics in young male and female Japanese quails supplemented with Saccharomyces cerevisiae. Quails were fed a basal diet containing no yeast or a basal diet supplemented with 1.5% (15 g per 1 kg of diet) of inactive S. cerevisiae, for a period of 42 days. S. cerevisiae inclusion had no effect on bone weight, length, and density, diaphysis geometry (cross-sectional area, wall thickness, moment of inertia) or on the mechanical strength (yield load, ultimate load, stiffness, Young's modulus, yield stress, ultimate stress). Yeast supplementation improved the morphology of the articular cartilage both in male and female quails, as the total thickness of the articular cartilage was significantly increased. In trabecular bone, an increase in real bone volume and trabecular thickness was observed in females supplemented with S. cerevisiae, while in males the increase in trabecular number was accompanied by a reduction in trabecular thickness. The results of the present study demonstrate that S. cerevisiae, through a sex-dependent action on the gut-bone axis, improved the structure of articular cartilage and microarchitecture of trabecular bone. The positive effects of S. cerevisiae supplementation were more evident in female quails.
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  • The chemical composition of snow provides insights on atmospheric transport of anthropogenic contaminants at different spatial scales. In this study, we assess how human activities influence the concentration of elements in the Andean mountain snow along a latitudinal transect throughout Chile. The concentration of seven elements (Al, Cu, Fe, Li, Mg, Mn and Zn) was associated to gaseous and particulate contaminants emitted at different spatial scales. Our results indicate carbon monoxide (CO) averaged at 20 km and nitrogen oxide (NOx) at 40 km as the main indicators of the chemical elements analyzed. CO was found to be a significant predictor of most element concentrations while concentrations of Cu, Mn, Mg and Zn were positively associated to emissions of NOx. Emission of 2.5 μm and 10 μm particulate matter averaged at different spatial scales was positively associated to concentration of Li. Finally, the concentration of Zn was positively associated to volatile organic compounds (VOC) averaged at 40 km around sampling sites. The association between air contaminants and chemical composition of snow suggests that regions with intensive anthropogenic pollution face reduced quality of freshwater originated from glacier and snow melting.While digital health solutions continue to grow in number and in complexity, the ability for stakeholders in healthcare to easily discern quality lags far behind. This challenge is in part due to the lack of a transparent and standardized approach to validation. Evaluation of mobile health applications (apps) is further burdened by low barriers to development and direct-to-user marketing, leading to a crowded and confusing landscape. https://www.selleckchem.com/products/dooku1.html In this context, we investigated the pragmatic application of a previously described framework for digital health validation, the Digital Health Scorecard, in a cohort of 22 popular mobile health oncology apps. The apps evaluated using this framework performed poorly, scoring 49.4% across all evaluation criteria as a group. Performance across component domains varied considerably with cost scoring highest at 100%, usability at 56.7%, technical at 37.3%, and clinical at 15.9%. satisfaction of prospectively determined end-user requirements derived from patient, family, and clinician consensus scored 37.2%. While cost outperformed consistently and usability was adequate, the results also suggested that apps suffered from significant technical limitations, were of limited clinical value, and generally did not do what end users wanted. These large gaps further support the need for transparent and standardized evaluation to help all stakeholders in healthcare improve the quality of mobile health.The COVID-19 pandemic (SARS-CoV-2) has revealed the need for proactive protocols to react and act, imposing preventive and restrictive countermeasures on time in any society. The extent to which confirmed cases can predict the morbidity and mortality in a society remains an unresolved issue. The research objective is therefore to test a generic model's predictability through time, based on percentage of confirmed cases on hospitalized patients, ICU patients and deceased. This study reports the explanatory and predictive ability of COVID-19-related healthcare data, such as whether there is a spread of a contagious and virulent virus in a society, and if so, whether the morbidity and mortality can be estimated in advance in the population. The model estimations stress the implementation of a pandemic strategy containing a proactive protocol entailing what, when, where, who and how countermeasures should be in place when a virulent virus (e.g. SARS-CoV-1, SARS-CoV-2 and MERS) or pandemic strikes next time. Several lessons for the future can be learnt from the reported model estimations. One lesson is that COVID-19-related morbidity and mortality in a population is indeed predictable. Another lesson is to have a proactive protocol of countermeasures in place.For determine the optimum position of the roof low roadway, the optimal solution is derived according to the response surface methodology. The UDEC numerical simulation of the overburden gives the porosity distribution of the strike fractured zone, the upper limit heights of the caving zone and the fractured zone are obtained as 18 m and 65 m, respectively. Based on the porosity distribution, the FLUENT numerical models of the goaf zone, air inlet roadway, air return roadway, working face and roof low roadway were established to simulate the gas concentration in the upper corner and gas drainage volume in roof low roadway during mining. Using the vertical and horizontal distance of the roof low roadway as the influencing factors, the experimental scheme of the position of the roof low roadway was designed according to the response surface method, and the response values were obtained from the FLUENT simulation experiments, predicting that the vertical and horizontal distances of the roof low roadway were 7.7 m and 5.9 m respectively when the interaction between the gas concentration in the upper corner and gas drainage volume in roof low roadway was optimal. Field tests showed that the average gas concentration in the upper corner and the average gas drainage volume in roof low roadway were 0.432% and 40.861 m3/min respectively, both of which were less than 10% of the error from the simulations. The design of the roof low roadway has effectively managed the gas accumulation problem in the upper corner.We presented a development of a custom lead shield and mouse strainer for targeted irradiation from the gamma-cell chamber. This study was divided into two parts i.e., to (i) fabricate the shield and strainer from a lead (Pb) and (ii) optimize the irradiation to the ****-bearing tumour model with 2 and 8 Gy absorbed doses. The lead shielding was fabricated into a cuboid shape with a canal on the top and a hole on the vertical side for the beam path. Respective deliveries doses of 28 and 75 Gy from gamma-cell were used to achieve 2 and 8 Gy absorbed doses at the tumour sites.The present work investigated the differences in the composition and internal microstructure of four types gypsum rock-fiber gypsum, transparent gypsum, alabaster, and ordinary gypsum by X-ray fluorescence spectrometry, X-ray diffraction, scanning electron microscope and Brazilian split test, and analyzed its effects on the tensile strength and fracture characteristics of gypsum rock. For alabaster, fiber gypsum, transparent gypsum, and ordinary gypsum, CaSO4·2H2O is the main component with 72.78%, 72.72%, 72.57%, and 71.51% content, and tensile strength of 1.79, 2.22, 3.22, and 4.35 MPa, respectively. In addition, the fracture line is arc-shaped, vertical, and zigzag for fiber gypsum, ordinary and transparent gypsums, and alabaster, respectively. On the microscopic level, fiber gypsum has an evident striated structure while the gradual increased pore development for alabaster, transparent gypsum, and ordinary gypsum. Gypsum rock has an obvious layered crystal structure with the increase of CaSO4·2H2O, contributing to the phenomenon with a larger grain size and lower tensile strength.
    The chemical composition of snow provides insights on atmospheric transport of anthropogenic contaminants at different spatial scales. In this study, we assess how human activities influence the concentration of elements in the Andean mountain snow along a latitudinal transect throughout Chile. The concentration of seven elements (Al, Cu, Fe, Li, Mg, Mn and Zn) was associated to gaseous and particulate contaminants emitted at different spatial scales. Our results indicate carbon monoxide (CO) averaged at 20 km and nitrogen oxide (NOx) at 40 km as the main indicators of the chemical elements analyzed. CO was found to be a significant predictor of most element concentrations while concentrations of Cu, Mn, Mg and Zn were positively associated to emissions of NOx. Emission of 2.5 μm and 10 μm particulate matter averaged at different spatial scales was positively associated to concentration of Li. Finally, the concentration of Zn was positively associated to volatile organic compounds (VOC) averaged at 40 km around sampling sites. The association between air contaminants and chemical composition of snow suggests that regions with intensive anthropogenic pollution face reduced quality of freshwater originated from glacier and snow melting.While digital health solutions continue to grow in number and in complexity, the ability for stakeholders in healthcare to easily discern quality lags far behind. This challenge is in part due to the lack of a transparent and standardized approach to validation. Evaluation of mobile health applications (apps) is further burdened by low barriers to development and direct-to-user marketing, leading to a crowded and confusing landscape. https://www.selleckchem.com/products/dooku1.html In this context, we investigated the pragmatic application of a previously described framework for digital health validation, the Digital Health Scorecard, in a cohort of 22 popular mobile health oncology apps. The apps evaluated using this framework performed poorly, scoring 49.4% across all evaluation criteria as a group. Performance across component domains varied considerably with cost scoring highest at 100%, usability at 56.7%, technical at 37.3%, and clinical at 15.9%. satisfaction of prospectively determined end-user requirements derived from patient, family, and clinician consensus scored 37.2%. While cost outperformed consistently and usability was adequate, the results also suggested that apps suffered from significant technical limitations, were of limited clinical value, and generally did not do what end users wanted. These large gaps further support the need for transparent and standardized evaluation to help all stakeholders in healthcare improve the quality of mobile health.The COVID-19 pandemic (SARS-CoV-2) has revealed the need for proactive protocols to react and act, imposing preventive and restrictive countermeasures on time in any society. The extent to which confirmed cases can predict the morbidity and mortality in a society remains an unresolved issue. The research objective is therefore to test a generic model's predictability through time, based on percentage of confirmed cases on hospitalized patients, ICU patients and deceased. This study reports the explanatory and predictive ability of COVID-19-related healthcare data, such as whether there is a spread of a contagious and virulent virus in a society, and if so, whether the morbidity and mortality can be estimated in advance in the population. The model estimations stress the implementation of a pandemic strategy containing a proactive protocol entailing what, when, where, who and how countermeasures should be in place when a virulent virus (e.g. SARS-CoV-1, SARS-CoV-2 and MERS) or pandemic strikes next time. Several lessons for the future can be learnt from the reported model estimations. One lesson is that COVID-19-related morbidity and mortality in a population is indeed predictable. Another lesson is to have a proactive protocol of countermeasures in place.For determine the optimum position of the roof low roadway, the optimal solution is derived according to the response surface methodology. The UDEC numerical simulation of the overburden gives the porosity distribution of the strike fractured zone, the upper limit heights of the caving zone and the fractured zone are obtained as 18 m and 65 m, respectively. Based on the porosity distribution, the FLUENT numerical models of the goaf zone, air inlet roadway, air return roadway, working face and roof low roadway were established to simulate the gas concentration in the upper corner and gas drainage volume in roof low roadway during mining. Using the vertical and horizontal distance of the roof low roadway as the influencing factors, the experimental scheme of the position of the roof low roadway was designed according to the response surface method, and the response values were obtained from the FLUENT simulation experiments, predicting that the vertical and horizontal distances of the roof low roadway were 7.7 m and 5.9 m respectively when the interaction between the gas concentration in the upper corner and gas drainage volume in roof low roadway was optimal. Field tests showed that the average gas concentration in the upper corner and the average gas drainage volume in roof low roadway were 0.432% and 40.861 m3/min respectively, both of which were less than 10% of the error from the simulations. The design of the roof low roadway has effectively managed the gas accumulation problem in the upper corner.We presented a development of a custom lead shield and mouse strainer for targeted irradiation from the gamma-cell chamber. This study was divided into two parts i.e., to (i) fabricate the shield and strainer from a lead (Pb) and (ii) optimize the irradiation to the mice-bearing tumour model with 2 and 8 Gy absorbed doses. The lead shielding was fabricated into a cuboid shape with a canal on the top and a hole on the vertical side for the beam path. Respective deliveries doses of 28 and 75 Gy from gamma-cell were used to achieve 2 and 8 Gy absorbed doses at the tumour sites.The present work investigated the differences in the composition and internal microstructure of four types gypsum rock-fiber gypsum, transparent gypsum, alabaster, and ordinary gypsum by X-ray fluorescence spectrometry, X-ray diffraction, scanning electron microscope and Brazilian split test, and analyzed its effects on the tensile strength and fracture characteristics of gypsum rock. For alabaster, fiber gypsum, transparent gypsum, and ordinary gypsum, CaSO4·2H2O is the main component with 72.78%, 72.72%, 72.57%, and 71.51% content, and tensile strength of 1.79, 2.22, 3.22, and 4.35 MPa, respectively. In addition, the fracture line is arc-shaped, vertical, and zigzag for fiber gypsum, ordinary and transparent gypsums, and alabaster, respectively. On the microscopic level, fiber gypsum has an evident striated structure while the gradual increased pore development for alabaster, transparent gypsum, and ordinary gypsum. Gypsum rock has an obvious layered crystal structure with the increase of CaSO4·2H2O, contributing to the phenomenon with a larger grain size and lower tensile strength.
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  • amined whether odor stimulation was required for the recovery of the olfactory bulb from atrophy. Our findings revealed that nasal inflammation and odor deprivation differentially induce layer-specific degeneration in the olfactory bulb, that loss of olfactory sensory neuron activity rather than neuroinflammation is a major cause of inflammation-induced olfactory bulb atrophy, and that odor stimulation is required for the olfactory bulb to recover from atrophy. Copyright © 2020 Hasegawa-Ishii et al.BACKGROUND/AIMS In the era of increasing incidence of syphilis globally, ocular syphilis is re-emerging as an important cause of uveitis. The aim of this study was to determine the clinical and laboratory characteristics of ocular- and neurosyphilis among individuals with and without HIV infection. METHODS Retrospective analysis of patients diagnosed with ocular syphilis presenting to Tygerberg Hospital, South Africa, over a 5-year period ending December 2018. RESULTS Two-hundred and fifteen eyes of 146 patients were included. HIV coinfection was present in 52.1% of the patients, with 23.7% of these patients being newly diagnosed on presentation. The median age was 36.5±9.8 years. Bilateral involvement occurred in 47.3%, with 68.1% of these patients being HIV positive. https://www.selleckchem.com/products/ly2584702.html The most frequent form of intraocular inflammation was posterior uveitis (40.9%), followed by panuveitis (38.1%), both of which were more predominant in HIV-positive eyes. Seventy-four per cent of all eyes had a visual acuity ≤20/50 and 40% less then 20/200 at presentation. A lumbar puncture was performed in 113 patients (77.4%). Sixteen patients had confirmed neurosyphilis and 27 probable neurosyphilis according to the UpToDate algorithms. CONCLUSION This study included the largest number of ocular syphilis cases with the largest proportion of HIV infection to date. Forty-three of 146 patients (37.0%) had neurosyphilis. HIV status must be determined in all patients with ocular syphilis since almost ¼ of patients were newly diagnosed with HIV infection by doing so. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.The origin of sex chromosomes has been hypothesized to involve the linkage of factors with antagonistic effects on male and female function. Garden asparagus (Asparagus officinalis L.) is an ideal species to test this hypothesis, as the X and Y chromosomes are cytologically homomorphic and evolved from an ancestral autosome pair in association with a shift from hermaphroditism to dioecy. Mutagenesis screens paired with single-molecule fluorescence in situ hybridization (smFISH) directly implicate Y-specific genes that respectively suppress female (pistil) development and are necessary for male (anther) development. Comparison of contiguous X and Y chromosome assemblies shows that hemizygosity underlies the loss of recombination between the genes suppressing female organogenesis (SUPPRESSOR OF FEMALE FUNCTION, SOFF) and promoting male function (TAPETAL DEVELOPMENT AND FUNCTION1, aspTDF1). We also experimentally demonstrate the function of aspTDF1. These findings provide direct evidence that sex chromosomes can function through linkage of two sex determination genes. © 2020 American Society of Plant Biologists. All rights reserved.Bacteria regulate the life histories of diverse eukaryotes, but relatively little is known about how eukaryotes interpret and respond to multiple bacterial cues encountered simultaneously. To explore how a eukaryote might respond to a combination of bioactive molecules from multiple bacteria, we treated the choanoflagellate Salpingoeca rosetta with two sets of bacterial cues, one that induces mating and the other that induces multicellular development. We found that simultaneous exposure to both sets of cues enhanced multicellular development in S. rosetta, eliciting both larger multicellular colonies and an increase in the number of colonies. Thus, rather than conveying conflicting sets of information, these distinct bacterial cues synergize to augment multicellular development. This study demonstrates how a eukaryote can integrate and modulate its response to cues from diverse bacteria, underscoring the potential impact of complex microbial communities on eukaryotic life histories.Importance Eukaryotic biolyright © 2020 Ireland et al.Drought is among the most destructive abiotic stresses limiting crop growth and yield worldwide. Although most research has focused on the contribution of plant-associated microbial communities to plant growth and disease suppression, far less is known about the microbes involved in drought resistance among desert plants. In the present study, we applied 16S rRNA gene amplicon sequencing to determine the structure of rhizosphere and root endosphere microbiomes of Alhagi sparsifolia. Compared to those of the rhizosphere, endosphere microbiomes had lower diversity but contained several taxa with higher relative abundance; many of these taxa were also present in the roots of other desert plants. We isolated a Pseudomonas strain (LTGT-11-2Z) that was prevalent in root endosphere microbiomes of A. sparsifolia and promoted drought resistance during incubation with wheat. Complete genome sequencing of LTGT-11-2Z revealed 1-aminocyclopropane-1-carboxylate deaminases, siderophore, spermidine, and colanic acid biosynthetic genes, and type VI secretion system genes, which are likely involved in biofilm formation and plant-microbe interactions. Together, these results indicate that drought-enduring plants harbor bacterial endophytes favorable to plant drought resistance, and suggest that novel endophytic bacterial taxa and gene resources may be discovered among these desert plants.Importance Understanding microbe-mediated plant resistance to drought is important for sustainable agriculture. We performed 16S rRNA gene amplicon sequencing and culture-dependent functional analyses of Alhagi sparsifolia rhizosphere and root endosphere microbiomes, and identified key endophytic bacterial taxa and their genes facilitating drought resistance in wheat. This study improves our understanding of plant drought resistance and provides new avenues for drought resistance improvement in crop plants under field conditions. Copyright © 2020 American Society for Microbiology.
    amined whether odor stimulation was required for the recovery of the olfactory bulb from atrophy. Our findings revealed that nasal inflammation and odor deprivation differentially induce layer-specific degeneration in the olfactory bulb, that loss of olfactory sensory neuron activity rather than neuroinflammation is a major cause of inflammation-induced olfactory bulb atrophy, and that odor stimulation is required for the olfactory bulb to recover from atrophy. Copyright © 2020 Hasegawa-Ishii et al.BACKGROUND/AIMS In the era of increasing incidence of syphilis globally, ocular syphilis is re-emerging as an important cause of uveitis. The aim of this study was to determine the clinical and laboratory characteristics of ocular- and neurosyphilis among individuals with and without HIV infection. METHODS Retrospective analysis of patients diagnosed with ocular syphilis presenting to Tygerberg Hospital, South Africa, over a 5-year period ending December 2018. RESULTS Two-hundred and fifteen eyes of 146 patients were included. HIV coinfection was present in 52.1% of the patients, with 23.7% of these patients being newly diagnosed on presentation. The median age was 36.5±9.8 years. Bilateral involvement occurred in 47.3%, with 68.1% of these patients being HIV positive. https://www.selleckchem.com/products/ly2584702.html The most frequent form of intraocular inflammation was posterior uveitis (40.9%), followed by panuveitis (38.1%), both of which were more predominant in HIV-positive eyes. Seventy-four per cent of all eyes had a visual acuity ≤20/50 and 40% less then 20/200 at presentation. A lumbar puncture was performed in 113 patients (77.4%). Sixteen patients had confirmed neurosyphilis and 27 probable neurosyphilis according to the UpToDate algorithms. CONCLUSION This study included the largest number of ocular syphilis cases with the largest proportion of HIV infection to date. Forty-three of 146 patients (37.0%) had neurosyphilis. HIV status must be determined in all patients with ocular syphilis since almost ¼ of patients were newly diagnosed with HIV infection by doing so. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.The origin of sex chromosomes has been hypothesized to involve the linkage of factors with antagonistic effects on male and female function. Garden asparagus (Asparagus officinalis L.) is an ideal species to test this hypothesis, as the X and Y chromosomes are cytologically homomorphic and evolved from an ancestral autosome pair in association with a shift from hermaphroditism to dioecy. Mutagenesis screens paired with single-molecule fluorescence in situ hybridization (smFISH) directly implicate Y-specific genes that respectively suppress female (pistil) development and are necessary for male (anther) development. Comparison of contiguous X and Y chromosome assemblies shows that hemizygosity underlies the loss of recombination between the genes suppressing female organogenesis (SUPPRESSOR OF FEMALE FUNCTION, SOFF) and promoting male function (TAPETAL DEVELOPMENT AND FUNCTION1, aspTDF1). We also experimentally demonstrate the function of aspTDF1. These findings provide direct evidence that sex chromosomes can function through linkage of two sex determination genes. © 2020 American Society of Plant Biologists. All rights reserved.Bacteria regulate the life histories of diverse eukaryotes, but relatively little is known about how eukaryotes interpret and respond to multiple bacterial cues encountered simultaneously. To explore how a eukaryote might respond to a combination of bioactive molecules from multiple bacteria, we treated the choanoflagellate Salpingoeca rosetta with two sets of bacterial cues, one that induces mating and the other that induces multicellular development. We found that simultaneous exposure to both sets of cues enhanced multicellular development in S. rosetta, eliciting both larger multicellular colonies and an increase in the number of colonies. Thus, rather than conveying conflicting sets of information, these distinct bacterial cues synergize to augment multicellular development. This study demonstrates how a eukaryote can integrate and modulate its response to cues from diverse bacteria, underscoring the potential impact of complex microbial communities on eukaryotic life histories.Importance Eukaryotic biolyright © 2020 Ireland et al.Drought is among the most destructive abiotic stresses limiting crop growth and yield worldwide. Although most research has focused on the contribution of plant-associated microbial communities to plant growth and disease suppression, far less is known about the microbes involved in drought resistance among desert plants. In the present study, we applied 16S rRNA gene amplicon sequencing to determine the structure of rhizosphere and root endosphere microbiomes of Alhagi sparsifolia. Compared to those of the rhizosphere, endosphere microbiomes had lower diversity but contained several taxa with higher relative abundance; many of these taxa were also present in the roots of other desert plants. We isolated a Pseudomonas strain (LTGT-11-2Z) that was prevalent in root endosphere microbiomes of A. sparsifolia and promoted drought resistance during incubation with wheat. Complete genome sequencing of LTGT-11-2Z revealed 1-aminocyclopropane-1-carboxylate deaminases, siderophore, spermidine, and colanic acid biosynthetic genes, and type VI secretion system genes, which are likely involved in biofilm formation and plant-microbe interactions. Together, these results indicate that drought-enduring plants harbor bacterial endophytes favorable to plant drought resistance, and suggest that novel endophytic bacterial taxa and gene resources may be discovered among these desert plants.Importance Understanding microbe-mediated plant resistance to drought is important for sustainable agriculture. We performed 16S rRNA gene amplicon sequencing and culture-dependent functional analyses of Alhagi sparsifolia rhizosphere and root endosphere microbiomes, and identified key endophytic bacterial taxa and their genes facilitating drought resistance in wheat. This study improves our understanding of plant drought resistance and provides new avenues for drought resistance improvement in crop plants under field conditions. Copyright © 2020 American Society for Microbiology.
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  • The regulation of stress in birds includes a complex interaction of neural systems affecting the hypothalamic-pituitary-adrenal (HPA) axis. In addition to the hypothalamic paraventricular nucleus, a structure called the nucleus of the hippocampal commissure likewise affects the output of pituitary stress hormones and appears to be unique to avian species. Within the anterior pituitary, the avian V1a and V1b receptors were found in corticotropes. Based on our studies with central administration of hormones in the chicken, corticotropic releasing hormone (CRH) is a more potent ACTH secretagogue than arginine vasotocin (AVT). In contrast, when applied peripherally, AVT is more efficacious. Co-administration of AVT and CRH peripherally, resulted in a synergistic stimulation of corticosterone release. Data suggest receptor oligomerization as one possible mechanism. In birds, vasotocin receptors associated with stress responses include the V1a and V1b receptors. Three-dimensional, homology-based structural models of the avian V1aR were built to test agonists and antagonists for each receptor that were screened by molecular docking to map their binding sites on each receptor. Additionally, binding affinity values for each available peptide antagonist to the V1aR and V1bR were determined. An anterior pituitary primary culture system was developed to determine how effective each antagonist blocked the function of each receptor in culture when stimulated by a combination of AVT/CRH administration. Use of an antagonist in subsequent in vivo studies identified the V1aR in regulating food intake in birds. The V1aR was likewise found in circumventricular organs of the brain, suggesting a possible function in stress. © 2020 Elsevier Inc. All rights reserved.Water can diffuse freely through the lipid bilayer at a limited rate or by water channel proteins in a rapid speed. Aquaporins (AQPs) are a family of membrane water channel proteins that mainly function as regulators of intracellular and intercellular water flow. They are distributed wildly in specific cell types in multiple organs and tissues. Since the first AQP was identified, 13 AQPs have been characterized in mammals. Structural analysis shows that AQPs are homotetramers with each AQP monomer containing six transmembrane α-helices, two half helices and five connecting loops with two conserved asparagine-proline-alanine (NPA) motifs embedding into the plasma membrane. AQPs are demonstrated to selectively transport water but also some other small molecules. The cellular functions of aquaporins are regulated mainly by posttranslational modifications, e.g., phosphorylation, ubiquitination, glycosylation, subcellular distribution, degradation, and protein interactions. https://www.selleckchem.com/products/brd3308.html Aquaporins, in particular, AQP2 plays an important role in some disease conditions such as water loss and gain. Insights into the molecular mechanisms regulating AQPs and its clinical significance are proving to be fundamental for development of novel therapeutic targets or reliable diagnostic and prognostic biomarkers. In this chapter, we summarize the molecular aspects of aquaporins which include the isoforms, crystal structure and the molecular mechanisms underlying the regulation of AQPs, with most focus on arginine vasopressin-regulated AQP2. © 2020 Elsevier Inc. All rights reserved.The physiological importance of vasopressin inactivation has long been appreciated, but the mechanisms and potential pathophysiologic roles of this process remain active subjects of research. Human Placental Leucine Aminopeptidase (P-LAP, encoded by the LNPEP gene) is an important determinant of vasopressinase activity during pregnancy and is associated with gestational diabetes insipidus and preeclampsia. Insulin-Regulated Aminopeptidase (IRAP), the rodent homologue of P-LAP, is coregulated with the insulin-responsive glucose transporter, GLUT4, in adipose and muscle cells. Recently, the Tether containing a UBX domain for GLUT4 (TUG) protein was shown to mediate the coordinated regulation of water and glucose homeostasis. TUG sequesters IRAP and GLUT4 intracellularly in the absence of insulin. Insulin and other stimuli cause the proteolytic cleavage of TUG to mobilize these proteins to the cell surface, where IRAP acts to terminate the activity of circulating vasopressin. Intriguingly, genetic variation in LNPEP is associated with the vasopressin response and mortality during sepsis, and increased copeptin, a marker of vasopressin secretion, is associated with cardiovascular and metabolic disease. We propose that in the setting of insulin resistance in muscle, increased cell-surface IRAP and accelerated vasopressin degradation cause a compensatory increase in vasopressin secretion. The increased vasopressin concentrations present at the kidneys then contribute to hypertension in the metabolic syndrome. Further analyses of metabolism and of vasopressin and copeptin may yield novel insights into a unified pathophysiologic mechanism linking insulin resistance and hypertension, and potentially other components of the metabolic syndrome, in humans. © 2020 Elsevier Inc. All rights reserved.We previously characterized the arginine vasotocin receptor sequences in the jawless vertebrate sea lamprey. These gene and protein sequences provide clues to the origins of the various arginine vasopressin and oxytocin receptor family members in jawed vertebrates. However, orthological relationships between the jawless and jawed receptors is unclear. The current work is a closer examination and comparison between these G protein-coupled receptor sequences of the lamprey, the early jawed vertebrate elephant shark, and the boned fish and tetrapods. Our objective was to gain more insight into the differentiation of key signaling domains, which may then aid in discerning the pattern and timing of whole genome duplication early in the vertebrate lineage. The lamprey receptors remain less differentiated than shark receptors, due in part to the single vasotocin ligand in the lamprey and the selection pressure of a second ligand, oxytocin, in the shark. However, variation in G proteins utilized among the V1A, V1B and oxytocin receptor types has also contributed to differentiation, as well as leading to a change in second-messenger signaling pathway in the V2-type receptors.
    The regulation of stress in birds includes a complex interaction of neural systems affecting the hypothalamic-pituitary-adrenal (HPA) axis. In addition to the hypothalamic paraventricular nucleus, a structure called the nucleus of the hippocampal commissure likewise affects the output of pituitary stress hormones and appears to be unique to avian species. Within the anterior pituitary, the avian V1a and V1b receptors were found in corticotropes. Based on our studies with central administration of hormones in the chicken, corticotropic releasing hormone (CRH) is a more potent ACTH secretagogue than arginine vasotocin (AVT). In contrast, when applied peripherally, AVT is more efficacious. Co-administration of AVT and CRH peripherally, resulted in a synergistic stimulation of corticosterone release. Data suggest receptor oligomerization as one possible mechanism. In birds, vasotocin receptors associated with stress responses include the V1a and V1b receptors. Three-dimensional, homology-based structural models of the avian V1aR were built to test agonists and antagonists for each receptor that were screened by molecular docking to map their binding sites on each receptor. Additionally, binding affinity values for each available peptide antagonist to the V1aR and V1bR were determined. An anterior pituitary primary culture system was developed to determine how effective each antagonist blocked the function of each receptor in culture when stimulated by a combination of AVT/CRH administration. Use of an antagonist in subsequent in vivo studies identified the V1aR in regulating food intake in birds. The V1aR was likewise found in circumventricular organs of the brain, suggesting a possible function in stress. © 2020 Elsevier Inc. All rights reserved.Water can diffuse freely through the lipid bilayer at a limited rate or by water channel proteins in a rapid speed. Aquaporins (AQPs) are a family of membrane water channel proteins that mainly function as regulators of intracellular and intercellular water flow. They are distributed wildly in specific cell types in multiple organs and tissues. Since the first AQP was identified, 13 AQPs have been characterized in mammals. Structural analysis shows that AQPs are homotetramers with each AQP monomer containing six transmembrane α-helices, two half helices and five connecting loops with two conserved asparagine-proline-alanine (NPA) motifs embedding into the plasma membrane. AQPs are demonstrated to selectively transport water but also some other small molecules. The cellular functions of aquaporins are regulated mainly by posttranslational modifications, e.g., phosphorylation, ubiquitination, glycosylation, subcellular distribution, degradation, and protein interactions. https://www.selleckchem.com/products/brd3308.html Aquaporins, in particular, AQP2 plays an important role in some disease conditions such as water loss and gain. Insights into the molecular mechanisms regulating AQPs and its clinical significance are proving to be fundamental for development of novel therapeutic targets or reliable diagnostic and prognostic biomarkers. In this chapter, we summarize the molecular aspects of aquaporins which include the isoforms, crystal structure and the molecular mechanisms underlying the regulation of AQPs, with most focus on arginine vasopressin-regulated AQP2. © 2020 Elsevier Inc. All rights reserved.The physiological importance of vasopressin inactivation has long been appreciated, but the mechanisms and potential pathophysiologic roles of this process remain active subjects of research. Human Placental Leucine Aminopeptidase (P-LAP, encoded by the LNPEP gene) is an important determinant of vasopressinase activity during pregnancy and is associated with gestational diabetes insipidus and preeclampsia. Insulin-Regulated Aminopeptidase (IRAP), the rodent homologue of P-LAP, is coregulated with the insulin-responsive glucose transporter, GLUT4, in adipose and muscle cells. Recently, the Tether containing a UBX domain for GLUT4 (TUG) protein was shown to mediate the coordinated regulation of water and glucose homeostasis. TUG sequesters IRAP and GLUT4 intracellularly in the absence of insulin. Insulin and other stimuli cause the proteolytic cleavage of TUG to mobilize these proteins to the cell surface, where IRAP acts to terminate the activity of circulating vasopressin. Intriguingly, genetic variation in LNPEP is associated with the vasopressin response and mortality during sepsis, and increased copeptin, a marker of vasopressin secretion, is associated with cardiovascular and metabolic disease. We propose that in the setting of insulin resistance in muscle, increased cell-surface IRAP and accelerated vasopressin degradation cause a compensatory increase in vasopressin secretion. The increased vasopressin concentrations present at the kidneys then contribute to hypertension in the metabolic syndrome. Further analyses of metabolism and of vasopressin and copeptin may yield novel insights into a unified pathophysiologic mechanism linking insulin resistance and hypertension, and potentially other components of the metabolic syndrome, in humans. © 2020 Elsevier Inc. All rights reserved.We previously characterized the arginine vasotocin receptor sequences in the jawless vertebrate sea lamprey. These gene and protein sequences provide clues to the origins of the various arginine vasopressin and oxytocin receptor family members in jawed vertebrates. However, orthological relationships between the jawless and jawed receptors is unclear. The current work is a closer examination and comparison between these G protein-coupled receptor sequences of the lamprey, the early jawed vertebrate elephant shark, and the boned fish and tetrapods. Our objective was to gain more insight into the differentiation of key signaling domains, which may then aid in discerning the pattern and timing of whole genome duplication early in the vertebrate lineage. The lamprey receptors remain less differentiated than shark receptors, due in part to the single vasotocin ligand in the lamprey and the selection pressure of a second ligand, oxytocin, in the shark. However, variation in G proteins utilized among the V1A, V1B and oxytocin receptor types has also contributed to differentiation, as well as leading to a change in second-messenger signaling pathway in the V2-type receptors.
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  • completion by specialty doctors (coefficient=-0.19; 95% CI -0.32 to -0.06; P=.005). Secondary analysis with the response time was done. There was also a significant inverse relationship between the frequency of specialty doctors' mobile EMR usage and the response time to consultation requests (coefficient=-0.18; 95% CI -0.30 to -0.04; P=.009). CONCLUSIONS Our findings suggest that frequent mobile EMR usage is associated with quicker response time to ED consultation requests. https://www.selleckchem.com/products/cilengitide-emd-121974-nsc-707544.html ©Kwang Yul Jung, SuJin Kim, Kihyung Kim, Eun Ju Lee, Kyunga Kim, Jeanhyoung Lee, Jong Soo Choi, Mira Kang, Dong Kyung Chang, Won Chul Cha. Originally published in JMIR mHealth and uHealth (http//mhealth.jmir.org), 14.02.2020.BACKGROUND Recent studies have thoughtfully and convincingly demonstrated the possibility of estimating the circadian rhythms of young adults' social activity by analyzing their telephone call-detail records (CDRs). In the field of health monitoring, this development may offer new opportunities for supervising a patient's health status by collecting objective, unobtrusive data about their daily social interactions. However, before considering this future perspective, whether and how similar results could be observed in other populations, including older ones, should be established. OBJECTIVE This study was designed specifically to address the circadian rhythms in the telephone calls of older adults. METHODS A longitudinal, 12-month dataset combining CDRs and questionnaire data from 26 volunteers aged 65 years or older was used to examine individual differences in the daily rhythms of telephone call activity. The study used outgoing CDRs only and worked with three specific telecommunication parameters (1) call findings suggest an opportunity to consider modern telephone technologies as potential sensors of daily activity. From a health care perspective, these sensors could be harnessed for unobtrusive monitoring purposes. ©Timothée Aubourg, Jacques Demongeot, Hervé Provost, Nicolas Vuillerme. Originally published in JMIR mHealth and uHealth (http//mhealth.jmir.org), 25.02.2020.The health care field has integrated advances into digital technology at an accelerating pace to improve health behavior, health care delivery, and cost-effectiveness of care. The realm of behavioral science has embraced this evolution of digital health, allowing for an exciting roadmap for advancing care by addressing the many challenges to the field via technological innovations. Digital therapeutics offer the potential to extend the reach of effective interventions at reduced cost and patient burden and to increase the potency of existing interventions. Intervention models have included the use of digital tools as supplements to standard care models, as tools that can replace a portion of treatment as usual, or as stand-alone tools accessed outside of care settings or direct to the consumer. To advance the potential public health impact of this promising line of research, multiple areas warrant further development and investigation. The Center for Technology and Behavioral Health (CTBH), a P30 Center of Exe Stanger, William C Torrey. Originally published in JMIR Mental Health (http//mental.jmir.org), 26.02.2020.BACKGROUND Many existing scales for microstressor assessment do not differentiate between objective (ie, observable) stressor events and stressful cognitions or concerns. They often mix items assessing objective stressor events with items measuring other aspects of stress, such as perceived stressor severity, the evoked stress reaction, or further consequences on health, which may result in spurious associations in studies that include other questionnaires that measure such constructs. Most scales were developed several decades ago; therefore, modern life stressors may not be represented. Ecological momentary assessment (EMA) allows for sampling of current behaviors and experiences in real time and in the natural habitat, thereby maximizing the generalization of the findings to real-life situations (ie, ecological validity) and minimizing recall bias. However, it has not been used for the validation of microstressor questionnaires so far. OBJECTIVE The aim is to develop a questionnaire that (1) allows for retn .001; severity beta=.73, 95% CI .59-.88, P less then .001) and the association did not change significantly over four subsequent weeks. CONCLUSIONS Our results provide evidence for the ecological validity of the MIMIS questionnaire. ©Andrea Chmitorz, Karolina Kurth, Lara K Mey, Mario Wenzel, Klaus Lieb, Oliver Tüscher, Thomas Kubiak, Raffael Kalisch. Originally published in JMIR Mental Health (http//mental.jmir.org), 24.02.2020.BACKGROUND To ensure quality care, clinicians need skills, knowledge, and attitudes related to technology that can be measured. OBJECTIVE This paper sought out competencies for mobile technologies and/or an approach to define them. METHODS A scoping review was conducted to answer the following research question, "What skills are needed for clinicians and trainees to provide quality care via mHealth, have they been published, and how can they be made measurable and reproducible to teach and assess them?" The review was conducted in accordance with the 6-stage scoping review process starting with a keyword search in PubMed/Medical Literature Analysis and Retrieval System Online, APA PsycNET, Cochrane, EMBASE, PsycINFO, Web of Science, and Scopus. The literature search focused on keywords in 4 concept areas (1) competencies, (2) mobile technologies, (3) telemedicine mode, and (4) health. Moreover, 2 authors independently, in parallel, screened the search results for potentially relevant studies based on titles a organizational change with technology and the creation of a positive electronic culture in a complex policy and regulatory environment. ©Donald M. Hilty, Steven Chan, John Torous, John Luo, Robert Boland. Originally published in JMIR mHealth and uHealth (http//mhealth.jmir.org), 21.02.2020.BACKGROUND Computable phenotypes have the ability to utilize data within the electronic health record (EHR) to identify patients with certain characteristics. Many computable phenotypes rely on multiple types of data within the EHR including prescription drug information. Hypertension (HTN)-related computable phenotypes are particularly dependent on the correct classification of antihypertensive prescription drug information, as well as corresponding diagnoses and blood pressure information. OBJECTIVE This study aimed to create an antihypertensive drug classification system to be utilized with EHR-based data as part of HTN-related computable phenotypes. METHODS We compared 4 different antihypertensive drug classification systems based off of 4 different methodologies and terminologies, including 3 RxNorm Concept Unique Identifier (RxCUI)-based classifications and 1 medication name-based classification. The RxCUI-based classifications utilized data from (1) the Drug Ontology, (2) the new Medication Reference Terminology, and (3) the Anatomical Therapeutic Chemical Classification System and DrugBank, whereas the medication name-based classification relied on antihypertensive drug names.
    completion by specialty doctors (coefficient=-0.19; 95% CI -0.32 to -0.06; P=.005). Secondary analysis with the response time was done. There was also a significant inverse relationship between the frequency of specialty doctors' mobile EMR usage and the response time to consultation requests (coefficient=-0.18; 95% CI -0.30 to -0.04; P=.009). CONCLUSIONS Our findings suggest that frequent mobile EMR usage is associated with quicker response time to ED consultation requests. https://www.selleckchem.com/products/cilengitide-emd-121974-nsc-707544.html ©Kwang Yul Jung, SuJin Kim, Kihyung Kim, Eun Ju Lee, Kyunga Kim, Jeanhyoung Lee, Jong Soo Choi, Mira Kang, Dong Kyung Chang, Won Chul Cha. Originally published in JMIR mHealth and uHealth (http//mhealth.jmir.org), 14.02.2020.BACKGROUND Recent studies have thoughtfully and convincingly demonstrated the possibility of estimating the circadian rhythms of young adults' social activity by analyzing their telephone call-detail records (CDRs). In the field of health monitoring, this development may offer new opportunities for supervising a patient's health status by collecting objective, unobtrusive data about their daily social interactions. However, before considering this future perspective, whether and how similar results could be observed in other populations, including older ones, should be established. OBJECTIVE This study was designed specifically to address the circadian rhythms in the telephone calls of older adults. METHODS A longitudinal, 12-month dataset combining CDRs and questionnaire data from 26 volunteers aged 65 years or older was used to examine individual differences in the daily rhythms of telephone call activity. The study used outgoing CDRs only and worked with three specific telecommunication parameters (1) call findings suggest an opportunity to consider modern telephone technologies as potential sensors of daily activity. From a health care perspective, these sensors could be harnessed for unobtrusive monitoring purposes. ©Timothée Aubourg, Jacques Demongeot, Hervé Provost, Nicolas Vuillerme. Originally published in JMIR mHealth and uHealth (http//mhealth.jmir.org), 25.02.2020.The health care field has integrated advances into digital technology at an accelerating pace to improve health behavior, health care delivery, and cost-effectiveness of care. The realm of behavioral science has embraced this evolution of digital health, allowing for an exciting roadmap for advancing care by addressing the many challenges to the field via technological innovations. Digital therapeutics offer the potential to extend the reach of effective interventions at reduced cost and patient burden and to increase the potency of existing interventions. Intervention models have included the use of digital tools as supplements to standard care models, as tools that can replace a portion of treatment as usual, or as stand-alone tools accessed outside of care settings or direct to the consumer. To advance the potential public health impact of this promising line of research, multiple areas warrant further development and investigation. The Center for Technology and Behavioral Health (CTBH), a P30 Center of Exe Stanger, William C Torrey. Originally published in JMIR Mental Health (http//mental.jmir.org), 26.02.2020.BACKGROUND Many existing scales for microstressor assessment do not differentiate between objective (ie, observable) stressor events and stressful cognitions or concerns. They often mix items assessing objective stressor events with items measuring other aspects of stress, such as perceived stressor severity, the evoked stress reaction, or further consequences on health, which may result in spurious associations in studies that include other questionnaires that measure such constructs. Most scales were developed several decades ago; therefore, modern life stressors may not be represented. Ecological momentary assessment (EMA) allows for sampling of current behaviors and experiences in real time and in the natural habitat, thereby maximizing the generalization of the findings to real-life situations (ie, ecological validity) and minimizing recall bias. However, it has not been used for the validation of microstressor questionnaires so far. OBJECTIVE The aim is to develop a questionnaire that (1) allows for retn .001; severity beta=.73, 95% CI .59-.88, P less then .001) and the association did not change significantly over four subsequent weeks. CONCLUSIONS Our results provide evidence for the ecological validity of the MIMIS questionnaire. ©Andrea Chmitorz, Karolina Kurth, Lara K Mey, Mario Wenzel, Klaus Lieb, Oliver Tüscher, Thomas Kubiak, Raffael Kalisch. Originally published in JMIR Mental Health (http//mental.jmir.org), 24.02.2020.BACKGROUND To ensure quality care, clinicians need skills, knowledge, and attitudes related to technology that can be measured. OBJECTIVE This paper sought out competencies for mobile technologies and/or an approach to define them. METHODS A scoping review was conducted to answer the following research question, "What skills are needed for clinicians and trainees to provide quality care via mHealth, have they been published, and how can they be made measurable and reproducible to teach and assess them?" The review was conducted in accordance with the 6-stage scoping review process starting with a keyword search in PubMed/Medical Literature Analysis and Retrieval System Online, APA PsycNET, Cochrane, EMBASE, PsycINFO, Web of Science, and Scopus. The literature search focused on keywords in 4 concept areas (1) competencies, (2) mobile technologies, (3) telemedicine mode, and (4) health. Moreover, 2 authors independently, in parallel, screened the search results for potentially relevant studies based on titles a organizational change with technology and the creation of a positive electronic culture in a complex policy and regulatory environment. ©Donald M. Hilty, Steven Chan, John Torous, John Luo, Robert Boland. Originally published in JMIR mHealth and uHealth (http//mhealth.jmir.org), 21.02.2020.BACKGROUND Computable phenotypes have the ability to utilize data within the electronic health record (EHR) to identify patients with certain characteristics. Many computable phenotypes rely on multiple types of data within the EHR including prescription drug information. Hypertension (HTN)-related computable phenotypes are particularly dependent on the correct classification of antihypertensive prescription drug information, as well as corresponding diagnoses and blood pressure information. OBJECTIVE This study aimed to create an antihypertensive drug classification system to be utilized with EHR-based data as part of HTN-related computable phenotypes. METHODS We compared 4 different antihypertensive drug classification systems based off of 4 different methodologies and terminologies, including 3 RxNorm Concept Unique Identifier (RxCUI)-based classifications and 1 medication name-based classification. The RxCUI-based classifications utilized data from (1) the Drug Ontology, (2) the new Medication Reference Terminology, and (3) the Anatomical Therapeutic Chemical Classification System and DrugBank, whereas the medication name-based classification relied on antihypertensive drug names.
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  • 8 days for stage 51, 14.8 days for stage 53, 10.7 days for stage 61, and only 7.3 days for stage 69; for pear trees, the advance was lower 10 days for stage 51, 9 days for stage 53, 6.7 days for stage 61, and only 2.1 days for stage 69. These findings, which might be extrapolated to similar environments, have important consequences in fruit growing, like the occurrence of climate accidents due to late frost, insect pollination, and application of pesticides and irrigation water.OBJECTIVES To test whether the difference in sensitivity or specificity between 2-mSv CT and conventional-dose CT (CDCT) for the diagnosis of appendicitis differs across subgroups of adolescents and young adults with suspected appendicitis. MATERIALS AND METHODS We used the per-protocol analysis data of a trial conducted between Dec 2013 and Aug 2016, including 2773 patients (median age [interquartile range], 28 [21-35] years) and 160 radiologists from 20 hospitals. We defined subgroups by sex, body size, clinical risk scores for appendicitis, time of CT examination (i.e., working vs. after hours), CT machines, radiologists' experience, previous site experience in 2-mSv CT, and site practice volume. We drew forest plots and tested for additive or multiplicative interaction between radiation dose and subgroup attributes. If any subgroup had fewer than 200 patients, we considered the results from that subgroup not meaningful. RESULTS For most subgroups, the 95% CIs for the differences in sensitivity and specifis inflammatory response scores, or hospitals with small appendectomy volume, as those subgroups in our data included limited numbers of patients.OBJECTIVES Coronary CT angiography (cCTA) has been used to non-invasively assess both the anatomical and hemodynamic significance of coronary stenosis. The current study investigated a new CFD-based method of evaluating pressure-flow curves across a stenosis to further enhance the diagnostic value of cCTA imaging. METHODS Fifty-eight patients who underwent both cCTA imaging and invasive coronary angiography (ICA) with fractional flow reserve (FFR) within 2 weeks were enrolled. The pressure-flow curve-derived parameters, viscous friction (VF) and expansion loss (EL), were compared with conventional cCTA parameters including percent area stenosis (AS) and minimum lumen area (MLA) by receiver operating characteristic (ROC) curve analysis. FFR ≤ 0.80 was used to indicate ischemia-causing stenosis. Correlations between FFR and other measurements were calculated by Spearman's rank correlation coefficient (rho). RESULTS Sixty-eight stenoses from 58 patients were analyzed. https://www.selleckchem.com/products/acy-738.html VF, EL, and AS were significantly larger in the group of FFR ≤ 0.8 while smaller MLA values were observed. The ROC-AUC of VF (0.91, 95% CI 0.81-0.96) was better than that of AS (change in AUC (ΔAUC) 0.27, p  less then  0.05) and MLA (ΔAUC 0.17, p  less then  0.05), and ROC-AUC of EL (0.90, 95%CI 0.80-0.96) was also better than that of AS (ΔAUC 0.26, p  less then  0.05) and MLA (ΔAUC 0.16, p  less then  0.05). FFR values correlated well with VF (rho = - 0.74 (95% CI - 0.83 to - 0.61, p  less then  0.0001) and EL (rho = - 0.74 (95% CI - 0.83 to - 0.61, p  less then  0.0001). CONCLUSION Pressure-flow curve-derived parameters enhance the diagnostic value of cCTA examination. KEY POINTS • Pressure-flow curve derived from cCTA can assess coronary lesion severity. • VF and EL are superior to cCTA alone for indicating ischemic lesions. • Pressure-flow curve derived from cCTA may assist in clinical decision-making.Increasing interest in the role of the complement system in systemic and renal disease is based on new pathophysiological and therapeutic insights of the recent past and particularly in genetic analyses in children with atypical hemolytic uremic syndrome (aHUS). aHUS is the prototypical systemic disease associated with excessive activation of the alternative complement pathway and manifests in the kidney, but also in other organs as thrombotic microangiopathy (TMA). Pathomechanisms discovered to induce the overactivation of the alternative complement pathway in aHUS led to the first successful therapeutic application of a C5b9 inhibitor. This suppression of the terminal complement cascade succeeded in inhibiting local tissue damage. Thereafter, thanks to advanced modern technologies, further systemic and renal diseases associated with mutations or auto-antibodies targeting the complement pathway were identified. Hereby, disease onset is frequently associated with an additional trigger, e.g. infection or hormonal alterations/imbalances, against the background of a pre-existing predisposition of the patient.Due to the growing understanding of the regulation, and thus the possibility of therapeutic modulation of the different complement pathways, and due to the increasing availability of a variety of drugs inhibiting the complement system, interest in complement-mediated systemic and renal disease has been steadily increasing, making it a "hot-topic" in medicine in recent years.In the original article, the corresponding author's given name and middle name were interchanged.OBJECTIVES X-ray is the fundamental imaging technique in both diagnosis and follow-up of rheumatic diseases. As patients often require sequential X-rays over many years, dose reduction is of great importance. New advanced noise reduction algorithms allow for a dose reduction of up to 50%. The aim of this study was to evaluate whether quality of low-dose images is non-inferior to standard-dose images and, therefore, application of this technique is possible in the context of imaging of rheumatic diseases. METHODS A total of 298 patients with known or suspected rheumatic disease were enrolled prospectively into this study, separated into three consecutive groups 80%, 64% and 50% tube charge reduction. All patients received imaging of one hand (laterality randomly assigned) with low-dose technique and imaging of the contralateral hand with standard-dose protocol. Images were evaluated by two independent readers who scored (on a scale of 1-5) the visualization of bony cortex, trabeculae and joint spaces of fingers and wrist separately.
    8 days for stage 51, 14.8 days for stage 53, 10.7 days for stage 61, and only 7.3 days for stage 69; for pear trees, the advance was lower 10 days for stage 51, 9 days for stage 53, 6.7 days for stage 61, and only 2.1 days for stage 69. These findings, which might be extrapolated to similar environments, have important consequences in fruit growing, like the occurrence of climate accidents due to late frost, insect pollination, and application of pesticides and irrigation water.OBJECTIVES To test whether the difference in sensitivity or specificity between 2-mSv CT and conventional-dose CT (CDCT) for the diagnosis of appendicitis differs across subgroups of adolescents and young adults with suspected appendicitis. MATERIALS AND METHODS We used the per-protocol analysis data of a trial conducted between Dec 2013 and Aug 2016, including 2773 patients (median age [interquartile range], 28 [21-35] years) and 160 radiologists from 20 hospitals. We defined subgroups by sex, body size, clinical risk scores for appendicitis, time of CT examination (i.e., working vs. after hours), CT machines, radiologists' experience, previous site experience in 2-mSv CT, and site practice volume. We drew forest plots and tested for additive or multiplicative interaction between radiation dose and subgroup attributes. If any subgroup had fewer than 200 patients, we considered the results from that subgroup not meaningful. RESULTS For most subgroups, the 95% CIs for the differences in sensitivity and specifis inflammatory response scores, or hospitals with small appendectomy volume, as those subgroups in our data included limited numbers of patients.OBJECTIVES Coronary CT angiography (cCTA) has been used to non-invasively assess both the anatomical and hemodynamic significance of coronary stenosis. The current study investigated a new CFD-based method of evaluating pressure-flow curves across a stenosis to further enhance the diagnostic value of cCTA imaging. METHODS Fifty-eight patients who underwent both cCTA imaging and invasive coronary angiography (ICA) with fractional flow reserve (FFR) within 2 weeks were enrolled. The pressure-flow curve-derived parameters, viscous friction (VF) and expansion loss (EL), were compared with conventional cCTA parameters including percent area stenosis (AS) and minimum lumen area (MLA) by receiver operating characteristic (ROC) curve analysis. FFR ≤ 0.80 was used to indicate ischemia-causing stenosis. Correlations between FFR and other measurements were calculated by Spearman's rank correlation coefficient (rho). RESULTS Sixty-eight stenoses from 58 patients were analyzed. https://www.selleckchem.com/products/acy-738.html VF, EL, and AS were significantly larger in the group of FFR ≤ 0.8 while smaller MLA values were observed. The ROC-AUC of VF (0.91, 95% CI 0.81-0.96) was better than that of AS (change in AUC (ΔAUC) 0.27, p  less then  0.05) and MLA (ΔAUC 0.17, p  less then  0.05), and ROC-AUC of EL (0.90, 95%CI 0.80-0.96) was also better than that of AS (ΔAUC 0.26, p  less then  0.05) and MLA (ΔAUC 0.16, p  less then  0.05). FFR values correlated well with VF (rho = - 0.74 (95% CI - 0.83 to - 0.61, p  less then  0.0001) and EL (rho = - 0.74 (95% CI - 0.83 to - 0.61, p  less then  0.0001). CONCLUSION Pressure-flow curve-derived parameters enhance the diagnostic value of cCTA examination. KEY POINTS • Pressure-flow curve derived from cCTA can assess coronary lesion severity. • VF and EL are superior to cCTA alone for indicating ischemic lesions. • Pressure-flow curve derived from cCTA may assist in clinical decision-making.Increasing interest in the role of the complement system in systemic and renal disease is based on new pathophysiological and therapeutic insights of the recent past and particularly in genetic analyses in children with atypical hemolytic uremic syndrome (aHUS). aHUS is the prototypical systemic disease associated with excessive activation of the alternative complement pathway and manifests in the kidney, but also in other organs as thrombotic microangiopathy (TMA). Pathomechanisms discovered to induce the overactivation of the alternative complement pathway in aHUS led to the first successful therapeutic application of a C5b9 inhibitor. This suppression of the terminal complement cascade succeeded in inhibiting local tissue damage. Thereafter, thanks to advanced modern technologies, further systemic and renal diseases associated with mutations or auto-antibodies targeting the complement pathway were identified. Hereby, disease onset is frequently associated with an additional trigger, e.g. infection or hormonal alterations/imbalances, against the background of a pre-existing predisposition of the patient.Due to the growing understanding of the regulation, and thus the possibility of therapeutic modulation of the different complement pathways, and due to the increasing availability of a variety of drugs inhibiting the complement system, interest in complement-mediated systemic and renal disease has been steadily increasing, making it a "hot-topic" in medicine in recent years.In the original article, the corresponding author's given name and middle name were interchanged.OBJECTIVES X-ray is the fundamental imaging technique in both diagnosis and follow-up of rheumatic diseases. As patients often require sequential X-rays over many years, dose reduction is of great importance. New advanced noise reduction algorithms allow for a dose reduction of up to 50%. The aim of this study was to evaluate whether quality of low-dose images is non-inferior to standard-dose images and, therefore, application of this technique is possible in the context of imaging of rheumatic diseases. METHODS A total of 298 patients with known or suspected rheumatic disease were enrolled prospectively into this study, separated into three consecutive groups 80%, 64% and 50% tube charge reduction. All patients received imaging of one hand (laterality randomly assigned) with low-dose technique and imaging of the contralateral hand with standard-dose protocol. Images were evaluated by two independent readers who scored (on a scale of 1-5) the visualization of bony cortex, trabeculae and joint spaces of fingers and wrist separately.
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  • We called these changes "lipid switches", as they alter the cell's status (e.g., proliferation, differentiation, death, etc.) in response to the modulation of membrane lipids. Indeed, this discovery enables therapeutic interventions that modify the bilayer's lipids, an approach known as membrane-lipid therapy (MLT) or melitherapy.When jammers move rapidly or an antenna platform travels at high speed, interference signals may move out of the null width in the array beampattern. Consequently, the interference suppression performance can be significantly degraded. To solve this problem, both the null broadening technique and robust adaptive beamforming are considered in this paper. A novel null broadening beamforming method based on reconstruction of the interference-plus-noise covariance (INC) matrix is proposed, in order to broaden the null width and offset the motion of the interfering signals. In the moving case, a single interference signal can have multiple directions of arrival, which is equivalent to the existence of multiple interference sources. In the reconstruction of the INC matrix, several virtual interference sources are set up around each of the actual jammers, such that the nulls can be broadened. Based on the reconstructed INC and signal-plus-noise covariance (SNC) matrices, the steering vector of the desired signal can be obtained by solving a new convex optimization problem. Simulation results show that the proposed beamformer can effectively broaden the null width and deepen the null depth, and its performance in interference cancellation is robust against fast-moving jammers or array platform motion. Furthermore, the null depth can be controlled by adjusting the power parameters in the reconstruction process and, if the direction of interference motion is known, the virtual interference sources can be set to achieve better performance.BACKGROUND Women with urinary incontinence incur an increased risk of elevated postvoid residual (PVR) volume and impaired voiding efficiency (i.e., voided percentage (Void%)), but the clinical significance of these parameters remains poorly described. Further characterization of PVR and voiding efficiency may thus be useful in refining the evaluation and management of urinary incontinence. This study aims to explore possible circadian variations in PVR and Void% in older women with stress (SUI), urge (UUI) and mixed urinary incontinence (MUI). METHODS A single center prospective study which enrolled a convenience sample of 90 older women who consulted a tertiary referral hospital for urinary incontinence. Participants underwent an extensive medical interview and were hospitalized to complete a 24-h frequency-volume chart (FVC) with PVR measurement after each void (FVCPVR). https://www.selleckchem.com/products/arq531.html RESULTS FVCPVR analysis demonstrated no differences in mean PVR and Void% between patients with SUI, UUI and MUI. Likewise, no daytime or nighttime differences were observed in mean PVR or Void% within or between groups. CONCLUSIONS No evidence of circadian variation in PVR or Void% was observed in older women with SUI, UUI or MUI.Dentin hypersensitivity is one of the most common clinical conditions usually associated with exposed dentinal tubules. The purpose of this study was to identify the potential of a graphene oxide quantum dot coating for mesoporous bioactive glass nanoparticles as a new material for the treatment of dentin hypersensitivity by investigating its mineralization activity and dentinal tubules sealing. Mesoporous bioactive glass nanoparticle was fabricated by modified sol-gel synthesis. X-ray diffraction was performed to characterize the synthesized nanoparticle Fourier transform infra-red spectroscopy investigated the functionalized surfaces. The distribution of the specific surface area and the pore size was measure by Pore size analysis. The morphology of sample was observed by Field Emission Scanning Electron Microscope (FESEM) and Field Emission Transmission Electron Microscope (FETEM). After disk-shaped specimens of mesoporous bioactive glass nanoparticles and graphene oxide quantum dot coated mesoporous bioacs nanoparticles sealed tightly the dentinal tubules. The graphene oxide quantum dot coating of mesoporous bioactive glass nanoparticles not only showed the excellent dentinal sealing ability but also rapidly promoted mineralization while minimizing the size increase by coating the mesoporous bioactive glass nanoparticles.The aim of the work is to study the metabolic characteristics of saliva in lung cancer for use in early diagnosis and determining the prognosis of the disease. The patient group included 425 lung cancer patients, 168 patients with non-cancerous lung diseases, and 550 healthy volunteers. Saliva samples were collected from all participants in the experiment before treatment and 34 biochemical saliva parameters were determined. Participants were monitored for six years to assess survival rates. The statistical analysis was performed by means of Statistica 10.0 (StatSoft) program and R package (version 3.2.3). To construct the classifier, the Random Forest method was used; the classification quality was assessed using the cross-validation method. Prognostic factors were analyzed by multivariate analysis using Cox's proportional hazard model in a backward step-wise fashion to adjust for potential confounding factors. A complex of metabolic changes occurring in saliva in lung cancer is described. Seven biochemical parameters were identified (catalase, triene conjugates, Schiff bases, pH, sialic acids, alkaline phosphatase, chlorides), which were used to construct the classifier. The sensitivity and specificity of the method were 69.5% and 87.5%, which is practically not inferior to the diagnostic characteristics of markers routinely used in the diagnosis of lung cancer. Significant independent factors in the poor prognosis of lung cancer are imidazole compounds (ICs) above 0.478 mmol/L and salivary lactate dehydrogenase activity below 545 U/L. Saliva has been shown to have great potential for the development of diagnostic and prognostic tests for lung cancer.Milk pre-processing steps-storage at 4 °C (with durations of 48, 72 or 96 h) and methods for microbiological stabilization of milk (1.4 μm microfiltration, thermization, thermization + bactofugation, pasteurization) are performed industrially before 0.1 µm-microfiltration (MF) of skimmed milk to ensure the microbiological quality of final fractions. The objective of this study was to better understand the influence of these pre-processing steps and their cumulative effects on MF performances (i.e., transmembrane pressure, and transmission and recovery of serum proteins (SP) in the permeate). Results showed that heat treatment of skimmed milk decreased ceramic MF performances, especially after a long 4 °C storage duration (96 h) of raw milk when milk was heat treated by pasteurization after 96 h of storage at 4 °C, the transmembrane pressure increased by 25% over a MF run of 330 min with a permeation flux of 75 L.h-1.m-2 and a volume reduction ratio of 3.0. After 48 h of storage at 4 °C, all other operating conditions being similar, the transmembrane pressure increased by only 6%.
    We called these changes "lipid switches", as they alter the cell's status (e.g., proliferation, differentiation, death, etc.) in response to the modulation of membrane lipids. Indeed, this discovery enables therapeutic interventions that modify the bilayer's lipids, an approach known as membrane-lipid therapy (MLT) or melitherapy.When jammers move rapidly or an antenna platform travels at high speed, interference signals may move out of the null width in the array beampattern. Consequently, the interference suppression performance can be significantly degraded. To solve this problem, both the null broadening technique and robust adaptive beamforming are considered in this paper. A novel null broadening beamforming method based on reconstruction of the interference-plus-noise covariance (INC) matrix is proposed, in order to broaden the null width and offset the motion of the interfering signals. In the moving case, a single interference signal can have multiple directions of arrival, which is equivalent to the existence of multiple interference sources. In the reconstruction of the INC matrix, several virtual interference sources are set up around each of the actual jammers, such that the nulls can be broadened. Based on the reconstructed INC and signal-plus-noise covariance (SNC) matrices, the steering vector of the desired signal can be obtained by solving a new convex optimization problem. Simulation results show that the proposed beamformer can effectively broaden the null width and deepen the null depth, and its performance in interference cancellation is robust against fast-moving jammers or array platform motion. Furthermore, the null depth can be controlled by adjusting the power parameters in the reconstruction process and, if the direction of interference motion is known, the virtual interference sources can be set to achieve better performance.BACKGROUND Women with urinary incontinence incur an increased risk of elevated postvoid residual (PVR) volume and impaired voiding efficiency (i.e., voided percentage (Void%)), but the clinical significance of these parameters remains poorly described. Further characterization of PVR and voiding efficiency may thus be useful in refining the evaluation and management of urinary incontinence. This study aims to explore possible circadian variations in PVR and Void% in older women with stress (SUI), urge (UUI) and mixed urinary incontinence (MUI). METHODS A single center prospective study which enrolled a convenience sample of 90 older women who consulted a tertiary referral hospital for urinary incontinence. Participants underwent an extensive medical interview and were hospitalized to complete a 24-h frequency-volume chart (FVC) with PVR measurement after each void (FVCPVR). https://www.selleckchem.com/products/arq531.html RESULTS FVCPVR analysis demonstrated no differences in mean PVR and Void% between patients with SUI, UUI and MUI. Likewise, no daytime or nighttime differences were observed in mean PVR or Void% within or between groups. CONCLUSIONS No evidence of circadian variation in PVR or Void% was observed in older women with SUI, UUI or MUI.Dentin hypersensitivity is one of the most common clinical conditions usually associated with exposed dentinal tubules. The purpose of this study was to identify the potential of a graphene oxide quantum dot coating for mesoporous bioactive glass nanoparticles as a new material for the treatment of dentin hypersensitivity by investigating its mineralization activity and dentinal tubules sealing. Mesoporous bioactive glass nanoparticle was fabricated by modified sol-gel synthesis. X-ray diffraction was performed to characterize the synthesized nanoparticle Fourier transform infra-red spectroscopy investigated the functionalized surfaces. The distribution of the specific surface area and the pore size was measure by Pore size analysis. The morphology of sample was observed by Field Emission Scanning Electron Microscope (FESEM) and Field Emission Transmission Electron Microscope (FETEM). After disk-shaped specimens of mesoporous bioactive glass nanoparticles and graphene oxide quantum dot coated mesoporous bioacs nanoparticles sealed tightly the dentinal tubules. The graphene oxide quantum dot coating of mesoporous bioactive glass nanoparticles not only showed the excellent dentinal sealing ability but also rapidly promoted mineralization while minimizing the size increase by coating the mesoporous bioactive glass nanoparticles.The aim of the work is to study the metabolic characteristics of saliva in lung cancer for use in early diagnosis and determining the prognosis of the disease. The patient group included 425 lung cancer patients, 168 patients with non-cancerous lung diseases, and 550 healthy volunteers. Saliva samples were collected from all participants in the experiment before treatment and 34 biochemical saliva parameters were determined. Participants were monitored for six years to assess survival rates. The statistical analysis was performed by means of Statistica 10.0 (StatSoft) program and R package (version 3.2.3). To construct the classifier, the Random Forest method was used; the classification quality was assessed using the cross-validation method. Prognostic factors were analyzed by multivariate analysis using Cox's proportional hazard model in a backward step-wise fashion to adjust for potential confounding factors. A complex of metabolic changes occurring in saliva in lung cancer is described. Seven biochemical parameters were identified (catalase, triene conjugates, Schiff bases, pH, sialic acids, alkaline phosphatase, chlorides), which were used to construct the classifier. The sensitivity and specificity of the method were 69.5% and 87.5%, which is practically not inferior to the diagnostic characteristics of markers routinely used in the diagnosis of lung cancer. Significant independent factors in the poor prognosis of lung cancer are imidazole compounds (ICs) above 0.478 mmol/L and salivary lactate dehydrogenase activity below 545 U/L. Saliva has been shown to have great potential for the development of diagnostic and prognostic tests for lung cancer.Milk pre-processing steps-storage at 4 °C (with durations of 48, 72 or 96 h) and methods for microbiological stabilization of milk (1.4 μm microfiltration, thermization, thermization + bactofugation, pasteurization) are performed industrially before 0.1 µm-microfiltration (MF) of skimmed milk to ensure the microbiological quality of final fractions. The objective of this study was to better understand the influence of these pre-processing steps and their cumulative effects on MF performances (i.e., transmembrane pressure, and transmission and recovery of serum proteins (SP) in the permeate). Results showed that heat treatment of skimmed milk decreased ceramic MF performances, especially after a long 4 °C storage duration (96 h) of raw milk when milk was heat treated by pasteurization after 96 h of storage at 4 °C, the transmembrane pressure increased by 25% over a MF run of 330 min with a permeation flux of 75 L.h-1.m-2 and a volume reduction ratio of 3.0. After 48 h of storage at 4 °C, all other operating conditions being similar, the transmembrane pressure increased by only 6%.
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  • Malaria and lymphatic filariasis (LF) are two leading and common mosquito-borne parasitic diseases worldwide. These two diseases are co-endemic in many tropical and sub-tropical regions and are known to share vectors. https://www.selleckchem.com/products/cep-18770.html The interactions between malaria and filarial parasites are poorly understood. Thus, this study aimed at establishing the interactions that occur between Brugia pahangi and Plasmodium berghei ANKA (PbA) co-infection in gerbils. Briefly, the gerbils were matched according to age, sex, and weight and grouped into filarial-only infection, PbA-only infection, co-infection, and control group. The parasitemia, survival and clinical assessment of the gerbils were monitored for a period of 30 days post Plasmodium infection. The immune responses of gerbils to both mono and co-infection were monitored. Findings show that co-infected gerbils have higher survival rate than PbA-infected gerbils. Food and water consumption were significantly reduced in both PbA-infected and co-infected gerbils, although loss of body weight, hypothermia, and anemia were less severe in co-infected gerbils. Plasmodium-infected gerbils also suffered hypoglycemia, which was not observed in co-infected gerbils. Furthermore, gerbil cytokine responses to co-infection were significantly higher than PbA-only-infected gerbils, which is being suggested as a factor for their increased longevity. Co-infected gerbils had significantly elicited interleukin-4, interferon-gamma, and tumor necrotic factor at early stage of infection than PbA-infected gerbils. Findings from this study suggest that B. pahangi infection protect against severe anemia and hypoglycemia, which are manifestations of PbA infection.As a result of climate change, causing high temperature, erratic precipitation, and extreme meteorological events, in recent times in Italy productivity of Maize is becoming less reliable. Climate change effects are accompanied by the increase in the presence of mycotoxins and various pathogens, which contribute to the reduction of the possibility of successfully producing Maize. In this framework, Proso Millet (Panicum miliaceum L.) may be an interesting alternative, as it is a relatively low-demanding crop, highly drought-resistant, and can be employed, similarly to Sorghum, in rotation, maintaining a certain amount of biodiversity and contributing to the revenue for the farmers. Moreover, Proso Millet has a very short cycle, and may be used as a catch crop, when other crops have failed or after their harvest. Millet used to be cultivated in ancient times in Italy, but then it was abandoned in favor of Maize, so now it is necessary to re-define proper agricultural practices and managements, as well as to rern during the season, enlightening for farmers the opportunity offered by Millet in Italy as a resilient crop.PURPOSE In this study, we investigated the effects of different concentration of propofol on cell viability of hippocampal neurons and explored the possible mechanism. PATIENTS AND METHODS Primary hippocampal neurons were cultured in vitro and treated with different concentration of propofol. MTT was used to examine the survival of neurons. Flow cytometry was used to detect the neuronal apoptosis. Western-blot analysis was used to examine the expression level of p-p38MAPK and p38MAPK. RESULTS We found that low concentration propofol (0.5 μM and 1 μM) promoted the cell survival rate; however, high concentration of propofol (10 μM,50 μM,100 μM,150 μM, and 200 μM) decreased the cell survival rate (P  less then  0.05). Flow cytometry showed that the neuronal apoptosis rate was decreased in 1 μM propofol group (P  less then  0.05), but was significantly higher in10μM, 100 μM and 200 μM groups in a concentration-dependent manner (P  less then  0.05 or P  less then  0.01). Western blot revealed that the propofol induced the phosphorylation of p38MAPK concentration-dependently and time-dependently. SB203580, one inhibitor of p38MAPK, increased the cell survival rate and decreased the cell apoptosis induced by high concentration of propofol. CONCLUSION Low concentration of propofol improved the survival rate of neurons, while high concentration of propofol promoted the cell apoptosis and decreased the cell viability. p38MAPK pathway is involved the effect of high concentration of propofol promoted on primary hippocampal neurons viability and apoptosis.Peritoneal metastases of high-grade serous ovarian cancer (HGSOC) are small-sized deposits with superficial growth toward the peritoneal cavity. It is unknown whether integrity of the peritoneal elastic lamina (PEL) correlates with the peritoneal tumor microenvironment (pTME) and whether neoadjuvant chemotherapy (NACT) affects the pTME. We explored integrity of PEL, composition of pTME, effects of NACT, and the prognostic implications in patients with extensive peritoneal metastases of HGSOC. Peritoneal samples (n = 69) were collected during cytoreductive surgery between 2003 and 2016. Clinical data were collected from medical charts. Integrity of PEL was evaluated with elastic stains. T cell (CD3, CD8) and M2-macrophage markers (CD163) were scored using algorithms created in definiens tissue studio. Patients with a disrupted PEL (n = 39; 57%), more often had residual disease after surgery (p = 0.050), compared to intact PEL. An intact PEL was associated with increased intraepithelial (ie) CD8+ cells (p = 0.032), but was not correlated with improved survival. After NACT, increased ieCD3+ cells were shown, compared to no-NACT (p = 0.044). Abundance of total CD3+ and CD8+ cells were associated with PFS (multivariate HR 0.40; 95%CI 0.23-0.69 and HR 0.49; 95%CI 0.29-0.83) and OS (HR 0.33; 95%CI 0.18-0.62 and HR 0.36; 95%CI 0.20-0.64). M2-macrophage infiltration was not correlated with survival. NACT increases abundance of ieCD3+ cells in peritoneal metastases of HGSOC. Increase of CD3+ and CD8+ cells is associated with improved PFS and OS. This suggests that CD3+ and CD8+ cells may function as prognostic biomarkers. Their role as predictive biomarker for chemotherapy or immunotherapy response in HGSOC warrants further research.
    Malaria and lymphatic filariasis (LF) are two leading and common mosquito-borne parasitic diseases worldwide. These two diseases are co-endemic in many tropical and sub-tropical regions and are known to share vectors. https://www.selleckchem.com/products/cep-18770.html The interactions between malaria and filarial parasites are poorly understood. Thus, this study aimed at establishing the interactions that occur between Brugia pahangi and Plasmodium berghei ANKA (PbA) co-infection in gerbils. Briefly, the gerbils were matched according to age, sex, and weight and grouped into filarial-only infection, PbA-only infection, co-infection, and control group. The parasitemia, survival and clinical assessment of the gerbils were monitored for a period of 30 days post Plasmodium infection. The immune responses of gerbils to both mono and co-infection were monitored. Findings show that co-infected gerbils have higher survival rate than PbA-infected gerbils. Food and water consumption were significantly reduced in both PbA-infected and co-infected gerbils, although loss of body weight, hypothermia, and anemia were less severe in co-infected gerbils. Plasmodium-infected gerbils also suffered hypoglycemia, which was not observed in co-infected gerbils. Furthermore, gerbil cytokine responses to co-infection were significantly higher than PbA-only-infected gerbils, which is being suggested as a factor for their increased longevity. Co-infected gerbils had significantly elicited interleukin-4, interferon-gamma, and tumor necrotic factor at early stage of infection than PbA-infected gerbils. Findings from this study suggest that B. pahangi infection protect against severe anemia and hypoglycemia, which are manifestations of PbA infection.As a result of climate change, causing high temperature, erratic precipitation, and extreme meteorological events, in recent times in Italy productivity of Maize is becoming less reliable. Climate change effects are accompanied by the increase in the presence of mycotoxins and various pathogens, which contribute to the reduction of the possibility of successfully producing Maize. In this framework, Proso Millet (Panicum miliaceum L.) may be an interesting alternative, as it is a relatively low-demanding crop, highly drought-resistant, and can be employed, similarly to Sorghum, in rotation, maintaining a certain amount of biodiversity and contributing to the revenue for the farmers. Moreover, Proso Millet has a very short cycle, and may be used as a catch crop, when other crops have failed or after their harvest. Millet used to be cultivated in ancient times in Italy, but then it was abandoned in favor of Maize, so now it is necessary to re-define proper agricultural practices and managements, as well as to rern during the season, enlightening for farmers the opportunity offered by Millet in Italy as a resilient crop.PURPOSE In this study, we investigated the effects of different concentration of propofol on cell viability of hippocampal neurons and explored the possible mechanism. PATIENTS AND METHODS Primary hippocampal neurons were cultured in vitro and treated with different concentration of propofol. MTT was used to examine the survival of neurons. Flow cytometry was used to detect the neuronal apoptosis. Western-blot analysis was used to examine the expression level of p-p38MAPK and p38MAPK. RESULTS We found that low concentration propofol (0.5 μM and 1 μM) promoted the cell survival rate; however, high concentration of propofol (10 μM,50 μM,100 μM,150 μM, and 200 μM) decreased the cell survival rate (P  less then  0.05). Flow cytometry showed that the neuronal apoptosis rate was decreased in 1 μM propofol group (P  less then  0.05), but was significantly higher in10μM, 100 μM and 200 μM groups in a concentration-dependent manner (P  less then  0.05 or P  less then  0.01). Western blot revealed that the propofol induced the phosphorylation of p38MAPK concentration-dependently and time-dependently. SB203580, one inhibitor of p38MAPK, increased the cell survival rate and decreased the cell apoptosis induced by high concentration of propofol. CONCLUSION Low concentration of propofol improved the survival rate of neurons, while high concentration of propofol promoted the cell apoptosis and decreased the cell viability. p38MAPK pathway is involved the effect of high concentration of propofol promoted on primary hippocampal neurons viability and apoptosis.Peritoneal metastases of high-grade serous ovarian cancer (HGSOC) are small-sized deposits with superficial growth toward the peritoneal cavity. It is unknown whether integrity of the peritoneal elastic lamina (PEL) correlates with the peritoneal tumor microenvironment (pTME) and whether neoadjuvant chemotherapy (NACT) affects the pTME. We explored integrity of PEL, composition of pTME, effects of NACT, and the prognostic implications in patients with extensive peritoneal metastases of HGSOC. Peritoneal samples (n = 69) were collected during cytoreductive surgery between 2003 and 2016. Clinical data were collected from medical charts. Integrity of PEL was evaluated with elastic stains. T cell (CD3, CD8) and M2-macrophage markers (CD163) were scored using algorithms created in definiens tissue studio. Patients with a disrupted PEL (n = 39; 57%), more often had residual disease after surgery (p = 0.050), compared to intact PEL. An intact PEL was associated with increased intraepithelial (ie) CD8+ cells (p = 0.032), but was not correlated with improved survival. After NACT, increased ieCD3+ cells were shown, compared to no-NACT (p = 0.044). Abundance of total CD3+ and CD8+ cells were associated with PFS (multivariate HR 0.40; 95%CI 0.23-0.69 and HR 0.49; 95%CI 0.29-0.83) and OS (HR 0.33; 95%CI 0.18-0.62 and HR 0.36; 95%CI 0.20-0.64). M2-macrophage infiltration was not correlated with survival. NACT increases abundance of ieCD3+ cells in peritoneal metastases of HGSOC. Increase of CD3+ and CD8+ cells is associated with improved PFS and OS. This suggests that CD3+ and CD8+ cells may function as prognostic biomarkers. Their role as predictive biomarker for chemotherapy or immunotherapy response in HGSOC warrants further research.
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