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Cardiac fibrosis is associated with fine particulate matter (PM2.5) exposure. In addition, whether high-fat diet (HFD) could exacerbate the PM2.5-induced cardiac injury was unevaluated. Thus, this study was aimed to investigate the combined effects of PM2.5 and HFD on cardiac fibrosis. The echocardiography and histopathological analysis showed that co-exposure of PM2.5 and HFD had a significant deleterious effect on both cardiac systolic and diastolic function accompanied the myofibril disorder and myocardial fibrosis in C57BL/6 J **** than exposed to PM2.5 or HFD alone. The augmented oxidative damage and increased α-SMA area percentage were detected in heart tissue of **** exposed to PM2.5 and HFD together. PM2.5 upregulated the expressions of cardiac fibrosis-related special markers, including collagen-I, collagen-III, TGF-β1, p-Smad3 and total Smad3, which had more pronounced activations in co-exposure group. Meanwhile, the factorial analysis exhibited the synergistic interaction regarded to the combined exposure of PM2.5 and HFD. Simultaneously, PM2.5 and palmitic acid increased intracellular ROS generation and activated the TGF-β1/Smad3 signaling pathway in cardiomyocytes. While the ROS scavenger NAC had effectively attenuated the ROS level and suppressed the TGF-β1/Smad3 signaling pathway. Taken together, our results demonstrated combined exposure to PM2.5 and HFD could aggravate cardiac fibrosis via activating the ROS/TGF-β1/Smad3 signaling pathway. BACKGROUND Banning smoking from public places may prevent adolescent smoking, but there is little evidence on impact of smoke-free policies (SFPs) from low and middle-income countries. This study assessed to what extent the adoption of local SPFs in Indonesia between 2007 and 2013 associated with adolescent smoking. METHODS Data on 239,170 adolescents (12-17 years old) were derived from the 2007 and 2013 national health surveys in 497 districts and 33 provinces. This study compared 2013 survey respondents living in districts/provinces that adopted SFPs between 2007 and 2013, with 2007 respondents and 2013 respondents in districts/provinces that did not adopt policies. https://www.selleckchem.com/products/thiamet-g.html Multilevel logistic regression analysis assessed whether SFP was associated with daily and non-daily smoking. We controlled for survey year, SFP in 2007, socio-demographics, and district characteristics. RESULTS Strong district SFPs was significantly associated with lower odds of daily smoking (OR0.81, 95 %CI0.69-0.97), but non-significantly with non-daily smoking (OR0.89, 95 %CI0.76-1.05). Strong provincial SFPs was not associated with daily smoking (OR1.02, 95 %CI0.84-1.25), but was associated with higher odds of non-daily smoking (OR1.22, 95 %CI0.99-1.51). Moderately strong SFPs did not consistently show associations in the same direction. For example, moderately strong provincial SFP was associated with higher odds of daily smoking (OR1.27, 95 %CI1.11-1.46) and lower odds of non-daily smoking (OR0.82, 95 %CI0.72-0.93). CONCLUSION We did not detect a consistent short-term effect of district and province-level smoke-free policies on adolescent smoking in Indonesia. Weak implementation and poor compliance may compromise effectiveness, which would call for improvement of SFP implementation in Indonesia. With the proposed Circular Economy Package, the European Union is striving to play a leading role in the implementation of recycling goals. The significantly increased recycling targets are just some of the defined objectives. However, to assess the Member States' attainment of the new recycling targets, the European Union still builds on a purely quantitative recycling rate assessment procedure that neglects to include qualitative recycling aspects. This circumstance could lead to additional quality losses in recycling processes because recyclers might tend to focus exclusively on higher quantities to achieve the stricter recycling targets on time. To prevent such a development, the aim of this study is to establish a complementary recycling indicator that combines quantitative and qualitative recycling aspects in one single metric. The basis of this assessment method is the statistical entropy approach, which enables the concentrating or diluting effect of a recycling process brought about through the separation or mixing of materials to be measured. The results of the statistical entropy metric will provide greater insight into recycling processes (or systems) and thereby yield enhanced information on the quantity and purity of recycling outputs. The simple structure of the new approach will allow enhanced comparisons between technologies as well as national recycling performance. A case study on plastic packaging recycling demonstrates that the new recycling indicator provides multifaceted findings relative to the hitherto purely quantitative recycling assessment data, hence enriching conclusions on the recycling performance. We investigated the distribution of 18 elements including non-volatiles (Al, P, Ca, Fe, Mg, K, Mn, Cu, Na, Cr, and Ni), semi-volatiles (Zn, Pb, Ag, As, and Cd), and volatiles (Hg and S) and compared their behaviors in two types of full-scale sewage sludge mono-incinerators, namely, a step-grate stoker (GS) and two fluidized bed incinerators (F-types), with the same feed sludge. Most of the non-volatile elements were enriched five-fold in all incinerated sewage sludge ash (ISSA), while the volatile S and Hg were barely enriched in ash due to the combustion components generated in the gas phase. While the semi-volatile elements were also enriched five-fold in the F-types, a different enrichment behavior was observed in the GS. Boiler and multi-cyclone dust in the GS showed higher enrichments of Pb and Cd compared to ash due to the combined effects of lower temperature and smaller particle size. Compared to the F-types, the GS generated ashes with lower toxicity as the major component (99.7%) and hazardous dust as the minor component. In the future, more attention should be paid to grate stokers in terms of recycling ISSA. Bayleyite is a highly hydrated uranyl tricarbonate mineral containing eighteen water molecules per formula unit. Due to this large water content, the correct description of its crystal structure is a great challenge for the first principles solid state methodology. In this work, the crystal structure, hydrogen bonding, mechanical properties and infrared spectrum of bayleyite, Mg2[UO2(CO3)3] · 18 H2O, have been investigated by means of Periodic Density Functional Theory methods using plane wave basis sets and pseudopotentials. The computed unit-cell parameters, interatomic distances, hydrogen bonding network geometry and the X-ray powder diffraction pattern of bayleyite reproduce successfully the experimental data, thus confirming the crystal structure determined from X-ray diffraction data. From the energy-optimized structure, the elastic properties and infrared spectrum have been determined using theoretical methods. The calculated elastic properties include the bulk modulus and its pressure derivatives, the Young and shear moduli, the Poisson ratio and the ductility, hardness and anisotropy indices.
Cardiac fibrosis is associated with fine particulate matter (PM2.5) exposure. In addition, whether high-fat diet (HFD) could exacerbate the PM2.5-induced cardiac injury was unevaluated. Thus, this study was aimed to investigate the combined effects of PM2.5 and HFD on cardiac fibrosis. The echocardiography and histopathological analysis showed that co-exposure of PM2.5 and HFD had a significant deleterious effect on both cardiac systolic and diastolic function accompanied the myofibril disorder and myocardial fibrosis in C57BL/6 J mice than exposed to PM2.5 or HFD alone. The augmented oxidative damage and increased α-SMA area percentage were detected in heart tissue of mice exposed to PM2.5 and HFD together. PM2.5 upregulated the expressions of cardiac fibrosis-related special markers, including collagen-I, collagen-III, TGF-β1, p-Smad3 and total Smad3, which had more pronounced activations in co-exposure group. Meanwhile, the factorial analysis exhibited the synergistic interaction regarded to the combined exposure of PM2.5 and HFD. Simultaneously, PM2.5 and palmitic acid increased intracellular ROS generation and activated the TGF-β1/Smad3 signaling pathway in cardiomyocytes. While the ROS scavenger NAC had effectively attenuated the ROS level and suppressed the TGF-β1/Smad3 signaling pathway. Taken together, our results demonstrated combined exposure to PM2.5 and HFD could aggravate cardiac fibrosis via activating the ROS/TGF-β1/Smad3 signaling pathway. BACKGROUND Banning smoking from public places may prevent adolescent smoking, but there is little evidence on impact of smoke-free policies (SFPs) from low and middle-income countries. This study assessed to what extent the adoption of local SPFs in Indonesia between 2007 and 2013 associated with adolescent smoking. METHODS Data on 239,170 adolescents (12-17 years old) were derived from the 2007 and 2013 national health surveys in 497 districts and 33 provinces. This study compared 2013 survey respondents living in districts/provinces that adopted SFPs between 2007 and 2013, with 2007 respondents and 2013 respondents in districts/provinces that did not adopt policies. https://www.selleckchem.com/products/thiamet-g.html Multilevel logistic regression analysis assessed whether SFP was associated with daily and non-daily smoking. We controlled for survey year, SFP in 2007, socio-demographics, and district characteristics. RESULTS Strong district SFPs was significantly associated with lower odds of daily smoking (OR0.81, 95 %CI0.69-0.97), but non-significantly with non-daily smoking (OR0.89, 95 %CI0.76-1.05). Strong provincial SFPs was not associated with daily smoking (OR1.02, 95 %CI0.84-1.25), but was associated with higher odds of non-daily smoking (OR1.22, 95 %CI0.99-1.51). Moderately strong SFPs did not consistently show associations in the same direction. For example, moderately strong provincial SFP was associated with higher odds of daily smoking (OR1.27, 95 %CI1.11-1.46) and lower odds of non-daily smoking (OR0.82, 95 %CI0.72-0.93). CONCLUSION We did not detect a consistent short-term effect of district and province-level smoke-free policies on adolescent smoking in Indonesia. Weak implementation and poor compliance may compromise effectiveness, which would call for improvement of SFP implementation in Indonesia. With the proposed Circular Economy Package, the European Union is striving to play a leading role in the implementation of recycling goals. The significantly increased recycling targets are just some of the defined objectives. However, to assess the Member States' attainment of the new recycling targets, the European Union still builds on a purely quantitative recycling rate assessment procedure that neglects to include qualitative recycling aspects. This circumstance could lead to additional quality losses in recycling processes because recyclers might tend to focus exclusively on higher quantities to achieve the stricter recycling targets on time. To prevent such a development, the aim of this study is to establish a complementary recycling indicator that combines quantitative and qualitative recycling aspects in one single metric. The basis of this assessment method is the statistical entropy approach, which enables the concentrating or diluting effect of a recycling process brought about through the separation or mixing of materials to be measured. The results of the statistical entropy metric will provide greater insight into recycling processes (or systems) and thereby yield enhanced information on the quantity and purity of recycling outputs. The simple structure of the new approach will allow enhanced comparisons between technologies as well as national recycling performance. A case study on plastic packaging recycling demonstrates that the new recycling indicator provides multifaceted findings relative to the hitherto purely quantitative recycling assessment data, hence enriching conclusions on the recycling performance. We investigated the distribution of 18 elements including non-volatiles (Al, P, Ca, Fe, Mg, K, Mn, Cu, Na, Cr, and Ni), semi-volatiles (Zn, Pb, Ag, As, and Cd), and volatiles (Hg and S) and compared their behaviors in two types of full-scale sewage sludge mono-incinerators, namely, a step-grate stoker (GS) and two fluidized bed incinerators (F-types), with the same feed sludge. Most of the non-volatile elements were enriched five-fold in all incinerated sewage sludge ash (ISSA), while the volatile S and Hg were barely enriched in ash due to the combustion components generated in the gas phase. While the semi-volatile elements were also enriched five-fold in the F-types, a different enrichment behavior was observed in the GS. Boiler and multi-cyclone dust in the GS showed higher enrichments of Pb and Cd compared to ash due to the combined effects of lower temperature and smaller particle size. Compared to the F-types, the GS generated ashes with lower toxicity as the major component (99.7%) and hazardous dust as the minor component. In the future, more attention should be paid to grate stokers in terms of recycling ISSA. Bayleyite is a highly hydrated uranyl tricarbonate mineral containing eighteen water molecules per formula unit. Due to this large water content, the correct description of its crystal structure is a great challenge for the first principles solid state methodology. In this work, the crystal structure, hydrogen bonding, mechanical properties and infrared spectrum of bayleyite, Mg2[UO2(CO3)3] · 18 H2O, have been investigated by means of Periodic Density Functional Theory methods using plane wave basis sets and pseudopotentials. The computed unit-cell parameters, interatomic distances, hydrogen bonding network geometry and the X-ray powder diffraction pattern of bayleyite reproduce successfully the experimental data, thus confirming the crystal structure determined from X-ray diffraction data. From the energy-optimized structure, the elastic properties and infrared spectrum have been determined using theoretical methods. The calculated elastic properties include the bulk modulus and its pressure derivatives, the Young and shear moduli, the Poisson ratio and the ductility, hardness and anisotropy indices.0 Comments 0 Shares 15 Views 0 ReviewsPlease log in to like, share and comment! -
The review deals with an expanding number of steroidal compounds that are capable of forming a metallogel providing a multitude of novel materials rich in their properties. The future of steroidal metallogels holds a myriad of potential applications as new intelligent materials. Detection of potentially harmful compounds without expensive instrumentation, entrapment of environmentally hazardous substances, and sensitive and selective nanomaterials represent only a few of these potential applications. This article reviews the design, synthesis, characterization, and applications of steroidal metallogels.Surface features are key to the transcellular transport of nanoparticles (NPs) across intestinal epithelium cells. Endowing the NPs with specific surface features adapted to the physiological conditions of the gastrointestinal (GI) tract holds great potential for the oral delivery of peptide/protein drugs. Therefore, in this work, a glutamic acid conjugated amphiphilic dendrimer (Glu-APD) was synthesized to replace the widely used 1,2-distearoyl-sn-glycero-3-phosphatidyl-ethanolamine-polyethylene glycol (DSPE-PEG) in the preparation of poly(lactic-co-glycolic acid) (PLGA)-based NPs. Glu-APD could provide the formed NPs (Glu-APD NPs) with specific surface features of dendritic oligopeptides. With such surface features, Glu-APD NPs exhibited a 7.78-fold increase in cellular uptake and a 2.17-fold increase in the transepithelial transport amount compared with those of the DSPE-PEG2000 modified counterparts (P NPs). Instead of a dominant clathrin-mediated endocytosis as shown by P NPs, Glu-APD can provide the NPsno-acid-associated transport of the related NPs, which might be considered as an advantage under physiological conditions. This work might also be considered as a valid reference for the construction of highly efficient oral delivery systems.Correction for 'Applications of Raman spectroscopy in the development of cell therapies state of the art and future perspectives' by Shreyas Rangan et al., Analyst, 2020, DOI 10.1039/c9an01811e.The alpha synuclein (α-syn) oligomer is one of the biomarkers used for the early diagnosis of Parkinson's disease. In this paper, two electrochemiluminescent (ECL) biosensors with an aptamer as the recognition element for α-syn oligomer detection were prepared. https://www.selleckchem.com/products/e7766-diammonium-salt.html A functionalized indium tin oxide (ITO) glass with metal-organic framework (MOF) materials provides an adequate sensing platform. Here the gold nanoparticles/metal organic frameworks (MOFs) composite (AuNPs@MOFs) using 3-aminopropyltrimethoxysilane as a binding agent, or to connect the MOFs onto the ITO directly via glutaraldehyde, both give a strong ECL emission for luminol, even under weak alkaline conditions. Thereafter, the thiolated or carboxylated aptamer was coalesced onto the MOF material functionalized electrode using an Au-S bond or amide bond via the classic 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide/N-hydroxysuccinimide (EDC-NHS) coupling, respectively. Thus, the ECL emission of the sensors significantly reduced after the specific binding of the α-syn oligomer to the aptamer. The good linear relationship of the ECL sensing signals upon the logarithm of the α-syn oligomer concentration were established, from 2.43 fM to 0.486 pM or 1.39 fM to 0.243 pM, and the limit of detection reached as low as 0.42 or 0.38 fM, for these two sensors. Both of the obtained sensors have the advantages of a high sensitivity, selectivity, and reproducibility and are capable of detecting the target in human serum.Radiotherapy is a commonly used method for curing cancers that appear on or just below the skin. Because of the dose build-up effect of X-rays, boluses made of various materials such as silica and wax are clinically applied on patients to increase the skin dose for an enhanced therapeutic effect. However, these commercial boluses can't conform well to the skin's surface with some curvature, resulting in radiation dose attenuation/loss at the lesion location. To address this limitation, we have developed a nano-titanium dioxide (nTiO2)-incorporated polyurethane/polyacrylamide (TPU/PAAm) hydrogel with multi-functions for fabricating a desirable bolus. The obtained hydrogel exhibits excellent mechanical, adhesive and self-healing properties and can fit closely to the surface of patients with any 3D curvature, eliminating the air gap which is a common problem for commercial boluses applied on patients. In particular, it is encouraging that when using the bolus made of TPU/PAAm hydrogel, the dose distribution including dose coverage, conformability and homogeneity within the planning target volume (PTV) is far superior to that when using the commercial bolus. A sufficient dose shifts toward the surface of the head model and is located only in the lesion site, demonstrating that TPU-PAAm hydrogel can provide an optimal dose distribution and be clinically effective for treating superficial tumors. Furthermore, nTiO2 particles feature uniform dispersion at the nanometer level in hydrogel after being modified by 2,2-bis(hydroxymethyl)propionic acid (DMPA) based on coordination chemistry, endowing the hydrogel with long-acting antibacterial ability. The good cell affinity of TPU-PAAm hydrogel is also confirmed in this study, further ensuring that the TPU-PAAm hydrogel prepared here is a desirable candidate as a tissue equivalent with the advantages of convenient use and effectiveness in radiotherapy.In spite of the widespread utilizations of lyotropic liquid crystals (LLCs) in food technology, as nanoreactors and in biomedical fields, the exact nature of their aqueous nanochannels which are deemed to dictate these applications are not completely understood. In this context, elucidation of the hydrogen bonding properties of the water molecules inside the nanochannels will contribute towards obtaining a complete picture of the LLC materials. In this study, we use two molecules exhibiting an excited state intramolecular proton transfer (ESIPT), fisetin and 3-hydroxyflavone, to determine the hydrogen bond donating and accepting parameters of the LLC water molecules. The steady state results imply a heterogeneity in the hydrogen bond accepting and donating properties inside the LLC nanochannels. Upon photoexcitation of the normal form of the ESIPT molecules, we notice that despite a reported general alcohol like polarity of the LLC nanochannels, the hydrogen bonding behaviour of the water molecules is similar to that of moderately polar aprotic solvents such as acetonitrile.
The review deals with an expanding number of steroidal compounds that are capable of forming a metallogel providing a multitude of novel materials rich in their properties. The future of steroidal metallogels holds a myriad of potential applications as new intelligent materials. Detection of potentially harmful compounds without expensive instrumentation, entrapment of environmentally hazardous substances, and sensitive and selective nanomaterials represent only a few of these potential applications. This article reviews the design, synthesis, characterization, and applications of steroidal metallogels.Surface features are key to the transcellular transport of nanoparticles (NPs) across intestinal epithelium cells. Endowing the NPs with specific surface features adapted to the physiological conditions of the gastrointestinal (GI) tract holds great potential for the oral delivery of peptide/protein drugs. Therefore, in this work, a glutamic acid conjugated amphiphilic dendrimer (Glu-APD) was synthesized to replace the widely used 1,2-distearoyl-sn-glycero-3-phosphatidyl-ethanolamine-polyethylene glycol (DSPE-PEG) in the preparation of poly(lactic-co-glycolic acid) (PLGA)-based NPs. Glu-APD could provide the formed NPs (Glu-APD NPs) with specific surface features of dendritic oligopeptides. With such surface features, Glu-APD NPs exhibited a 7.78-fold increase in cellular uptake and a 2.17-fold increase in the transepithelial transport amount compared with those of the DSPE-PEG2000 modified counterparts (P NPs). Instead of a dominant clathrin-mediated endocytosis as shown by P NPs, Glu-APD can provide the NPsno-acid-associated transport of the related NPs, which might be considered as an advantage under physiological conditions. This work might also be considered as a valid reference for the construction of highly efficient oral delivery systems.Correction for 'Applications of Raman spectroscopy in the development of cell therapies state of the art and future perspectives' by Shreyas Rangan et al., Analyst, 2020, DOI 10.1039/c9an01811e.The alpha synuclein (α-syn) oligomer is one of the biomarkers used for the early diagnosis of Parkinson's disease. In this paper, two electrochemiluminescent (ECL) biosensors with an aptamer as the recognition element for α-syn oligomer detection were prepared. https://www.selleckchem.com/products/e7766-diammonium-salt.html A functionalized indium tin oxide (ITO) glass with metal-organic framework (MOF) materials provides an adequate sensing platform. Here the gold nanoparticles/metal organic frameworks (MOFs) composite (AuNPs@MOFs) using 3-aminopropyltrimethoxysilane as a binding agent, or to connect the MOFs onto the ITO directly via glutaraldehyde, both give a strong ECL emission for luminol, even under weak alkaline conditions. Thereafter, the thiolated or carboxylated aptamer was coalesced onto the MOF material functionalized electrode using an Au-S bond or amide bond via the classic 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide/N-hydroxysuccinimide (EDC-NHS) coupling, respectively. Thus, the ECL emission of the sensors significantly reduced after the specific binding of the α-syn oligomer to the aptamer. The good linear relationship of the ECL sensing signals upon the logarithm of the α-syn oligomer concentration were established, from 2.43 fM to 0.486 pM or 1.39 fM to 0.243 pM, and the limit of detection reached as low as 0.42 or 0.38 fM, for these two sensors. Both of the obtained sensors have the advantages of a high sensitivity, selectivity, and reproducibility and are capable of detecting the target in human serum.Radiotherapy is a commonly used method for curing cancers that appear on or just below the skin. Because of the dose build-up effect of X-rays, boluses made of various materials such as silica and wax are clinically applied on patients to increase the skin dose for an enhanced therapeutic effect. However, these commercial boluses can't conform well to the skin's surface with some curvature, resulting in radiation dose attenuation/loss at the lesion location. To address this limitation, we have developed a nano-titanium dioxide (nTiO2)-incorporated polyurethane/polyacrylamide (TPU/PAAm) hydrogel with multi-functions for fabricating a desirable bolus. The obtained hydrogel exhibits excellent mechanical, adhesive and self-healing properties and can fit closely to the surface of patients with any 3D curvature, eliminating the air gap which is a common problem for commercial boluses applied on patients. In particular, it is encouraging that when using the bolus made of TPU/PAAm hydrogel, the dose distribution including dose coverage, conformability and homogeneity within the planning target volume (PTV) is far superior to that when using the commercial bolus. A sufficient dose shifts toward the surface of the head model and is located only in the lesion site, demonstrating that TPU-PAAm hydrogel can provide an optimal dose distribution and be clinically effective for treating superficial tumors. Furthermore, nTiO2 particles feature uniform dispersion at the nanometer level in hydrogel after being modified by 2,2-bis(hydroxymethyl)propionic acid (DMPA) based on coordination chemistry, endowing the hydrogel with long-acting antibacterial ability. The good cell affinity of TPU-PAAm hydrogel is also confirmed in this study, further ensuring that the TPU-PAAm hydrogel prepared here is a desirable candidate as a tissue equivalent with the advantages of convenient use and effectiveness in radiotherapy.In spite of the widespread utilizations of lyotropic liquid crystals (LLCs) in food technology, as nanoreactors and in biomedical fields, the exact nature of their aqueous nanochannels which are deemed to dictate these applications are not completely understood. In this context, elucidation of the hydrogen bonding properties of the water molecules inside the nanochannels will contribute towards obtaining a complete picture of the LLC materials. In this study, we use two molecules exhibiting an excited state intramolecular proton transfer (ESIPT), fisetin and 3-hydroxyflavone, to determine the hydrogen bond donating and accepting parameters of the LLC water molecules. The steady state results imply a heterogeneity in the hydrogen bond accepting and donating properties inside the LLC nanochannels. Upon photoexcitation of the normal form of the ESIPT molecules, we notice that despite a reported general alcohol like polarity of the LLC nanochannels, the hydrogen bonding behaviour of the water molecules is similar to that of moderately polar aprotic solvents such as acetonitrile.0 Comments 0 Shares 15 Views 0 Reviews -
PURPOSE Radical nephrectomy (RN) and partial nephrectomy (PN) are widely used for early-stage renal cell carcinoma (RCC). However, the results were inconsistent while comparing the efficiency of RN and PN. This study aimed to assess the perioperative effectiveness of RN and PN for treating RCC. MATERIAL AND METHODS PubMed, Embase, and the Cochrane Library electronic database were searched for studies on adults with RCC comparing RN and PN published until September 2019. The perioperative efficacy and safety outcomes were calculated using odds ratio (OR) and standard mean difference (SMD) with 95% confidence intervals (CIs) for dichotomous and continuous data, respectively. Subgroup analysis were conducted based on tumor stage and surgery methods for evaluation of the treatment effect on specific subsets. RESULTS A total of 23 studies involving 30,018 patients with RCC were included in this meta-analysis. https://www.selleckchem.com/products/sar439859.html Notably, RCC treated with PN was associated with low incidences of hospital mortality (OR 0.58; 95% CI 0.38-0.89; P = 0.013) and reoperation rate (OR 0.74; 95% CI 0.58-0.95; P = 0.016) as compared to RN. However, PN was associated with an increased risk of overall postoperative complications (OR 1.40; 95% CI 1.17-1.68, P less then 0.001), postoperative hemorrhagic complications (OR 1.92; 95% CI 1.28-2.87, P = 0.002), and urinary fistula (OR 17.65; 95% CI 5.35-58.30, P less then 0.001) as compared to RN. CONCLUSION These findings suggested that PN was associated with lower incidences of hospital mortality and reoperation rate, whereas RN was associated with fewer complications.OBJECTIVE The aim of this study was to investigate how obesity was covered in Chinese newspapers from 1999 to 2018, demonstrating the trends and the characteristics of obesity-related news. METHODS Content analysis was conducted to analyze a total of 358 news articles spanning two decades (1999-2018). We explored how Chinese newspapers portrayed obesity in terms of the evidence/sources cited in articles, its impacts, drivers/causes, and solutions; and how such portrayals have evolved over time. We further compared the articles across different types of newspapers (government-sponsored vs. commercial), two subpopulations (children vs. adults), and periods of time (1999-2008 vs. 2009-2018). RESULTS Results showed that medical experts' interviews and statistics were the two most cited types of evidence in the articles. When discussing causes and solutions of obesity, factors pertaining to personal lifestyles were mentioned most frequently. Compared to psychological and social impacts, physical health risk was stressed more often. Compared with commercial newspapers, government-funded newspapers mentioned societal drivers of obesity and suggested reforming schools more frequently. Such differences were also found between coverage of child obesity and adult obesity. Our research, furthermore, revealed significant differences of media coverage of obesity across the two decades. CONCLUSIONS Our findings indicate that obesity was generally depicted as a "self-regulated epidemic" in Chinese newspapers. Although the revealed causes and consequences of obesity are evidently related to individual factors, more attention should be directed to the roles that the government, media, and the society can play in preventing obesity and mitigating related social/economic burden. LEVEL OF EVIDENCE Level V, cross-sectional descriptive study.OVERVIEW Lung cancer is one of the deadliest cancers in the world. Its histological classification depends on early diagnosis and successful treatment. Therefore, having specific biomarkers for a quick sorting widens the successful output of lung cancer treatment. MATERIAL AND METHODS High-throughput sequencing (RNA-seq) was performed of small cohorts of BioBanco samples from healthy and tumour cells from lung adenocarcinoma (LUAD) and squamous cell carcinoma of the lung (lSCC). RNA-seq samples from small cell lung cancer (SCLC) were downloaded from databases. A bioinformatic workflow has been programmed for the identification of differentially expressed genes (DEGs). RESULTS A total of 4777 DEGs were differentially expressed in SCLC, 3676 DEGs were in lSCC, while the lowest number of DEGs, 2819, appeared in LUAD. Among them, 945 DEGs were common to the three histological types. Once validated their expression profile and their survival predictive capacity in large, public cohorts, three DEGs can be exclusively considered as diagnostic biomarkers, three as prognosis biomarkers, and other three exhibit both diagnosis and prognosis capabilities. CONCLUSIONS This prospective study presents evidences for the diagnostic and prognostic capabilities of expression changes in CAPN8-2, TMC5 and **** in LUAD, while they are non-significant in SCLC and lSCC. Their translation to clinical practice is proposed.Mesenchymal stem cells are a highly promising source of cells for regeneration therapy because of their multilineage differentiation potential. However, distinct markers for mesenchymal stem cells are not well-established. To identify new candidate marker genes for multipotent human dental pulp stem cells, we analyzed the characteristics and gene expression profiles of cell clones obtained from a single dental pulp specimen derived from an 11-year-old female patient. Fifty colony-forming single cell-derived clones were separately cultured until the cessation of growth. These clones varied in their proliferation abilities and surface marker (STRO-1 and CD146) expression patterns, as well as their odontogenic, adipogenic, and chondrogenic differentiation potentials. Four clones maintained their original differentiation potentials during long-term culture. Gene expression profile by DNA microarray analysis of five representative clones identified 1227 genes that were related to multipotency. Ninety of these 1227 genes overlapped with genes reportedly involved in 'stemness or differentiation'. Based on the predicted locations of expressed protein products and large changes in expression levels, 14 of the 90 genes were selected as candidate dental pulp stem cell markers, particularly in relation to their multipotency characteristics. This characterization of cell clones obtained from a single specimen of human dental pulp provided information regarding new candidate marker genes for multipotent dental pulp stem cells, which could facilitate efficient analysis or enrichment of multipotent stem cells.
PURPOSE Radical nephrectomy (RN) and partial nephrectomy (PN) are widely used for early-stage renal cell carcinoma (RCC). However, the results were inconsistent while comparing the efficiency of RN and PN. This study aimed to assess the perioperative effectiveness of RN and PN for treating RCC. MATERIAL AND METHODS PubMed, Embase, and the Cochrane Library electronic database were searched for studies on adults with RCC comparing RN and PN published until September 2019. The perioperative efficacy and safety outcomes were calculated using odds ratio (OR) and standard mean difference (SMD) with 95% confidence intervals (CIs) for dichotomous and continuous data, respectively. Subgroup analysis were conducted based on tumor stage and surgery methods for evaluation of the treatment effect on specific subsets. RESULTS A total of 23 studies involving 30,018 patients with RCC were included in this meta-analysis. https://www.selleckchem.com/products/sar439859.html Notably, RCC treated with PN was associated with low incidences of hospital mortality (OR 0.58; 95% CI 0.38-0.89; P = 0.013) and reoperation rate (OR 0.74; 95% CI 0.58-0.95; P = 0.016) as compared to RN. However, PN was associated with an increased risk of overall postoperative complications (OR 1.40; 95% CI 1.17-1.68, P less then 0.001), postoperative hemorrhagic complications (OR 1.92; 95% CI 1.28-2.87, P = 0.002), and urinary fistula (OR 17.65; 95% CI 5.35-58.30, P less then 0.001) as compared to RN. CONCLUSION These findings suggested that PN was associated with lower incidences of hospital mortality and reoperation rate, whereas RN was associated with fewer complications.OBJECTIVE The aim of this study was to investigate how obesity was covered in Chinese newspapers from 1999 to 2018, demonstrating the trends and the characteristics of obesity-related news. METHODS Content analysis was conducted to analyze a total of 358 news articles spanning two decades (1999-2018). We explored how Chinese newspapers portrayed obesity in terms of the evidence/sources cited in articles, its impacts, drivers/causes, and solutions; and how such portrayals have evolved over time. We further compared the articles across different types of newspapers (government-sponsored vs. commercial), two subpopulations (children vs. adults), and periods of time (1999-2008 vs. 2009-2018). RESULTS Results showed that medical experts' interviews and statistics were the two most cited types of evidence in the articles. When discussing causes and solutions of obesity, factors pertaining to personal lifestyles were mentioned most frequently. Compared to psychological and social impacts, physical health risk was stressed more often. Compared with commercial newspapers, government-funded newspapers mentioned societal drivers of obesity and suggested reforming schools more frequently. Such differences were also found between coverage of child obesity and adult obesity. Our research, furthermore, revealed significant differences of media coverage of obesity across the two decades. CONCLUSIONS Our findings indicate that obesity was generally depicted as a "self-regulated epidemic" in Chinese newspapers. Although the revealed causes and consequences of obesity are evidently related to individual factors, more attention should be directed to the roles that the government, media, and the society can play in preventing obesity and mitigating related social/economic burden. LEVEL OF EVIDENCE Level V, cross-sectional descriptive study.OVERVIEW Lung cancer is one of the deadliest cancers in the world. Its histological classification depends on early diagnosis and successful treatment. Therefore, having specific biomarkers for a quick sorting widens the successful output of lung cancer treatment. MATERIAL AND METHODS High-throughput sequencing (RNA-seq) was performed of small cohorts of BioBanco samples from healthy and tumour cells from lung adenocarcinoma (LUAD) and squamous cell carcinoma of the lung (lSCC). RNA-seq samples from small cell lung cancer (SCLC) were downloaded from databases. A bioinformatic workflow has been programmed for the identification of differentially expressed genes (DEGs). RESULTS A total of 4777 DEGs were differentially expressed in SCLC, 3676 DEGs were in lSCC, while the lowest number of DEGs, 2819, appeared in LUAD. Among them, 945 DEGs were common to the three histological types. Once validated their expression profile and their survival predictive capacity in large, public cohorts, three DEGs can be exclusively considered as diagnostic biomarkers, three as prognosis biomarkers, and other three exhibit both diagnosis and prognosis capabilities. CONCLUSIONS This prospective study presents evidences for the diagnostic and prognostic capabilities of expression changes in CAPN8-2, TMC5 and MUC1 in LUAD, while they are non-significant in SCLC and lSCC. Their translation to clinical practice is proposed.Mesenchymal stem cells are a highly promising source of cells for regeneration therapy because of their multilineage differentiation potential. However, distinct markers for mesenchymal stem cells are not well-established. To identify new candidate marker genes for multipotent human dental pulp stem cells, we analyzed the characteristics and gene expression profiles of cell clones obtained from a single dental pulp specimen derived from an 11-year-old female patient. Fifty colony-forming single cell-derived clones were separately cultured until the cessation of growth. These clones varied in their proliferation abilities and surface marker (STRO-1 and CD146) expression patterns, as well as their odontogenic, adipogenic, and chondrogenic differentiation potentials. Four clones maintained their original differentiation potentials during long-term culture. Gene expression profile by DNA microarray analysis of five representative clones identified 1227 genes that were related to multipotency. Ninety of these 1227 genes overlapped with genes reportedly involved in 'stemness or differentiation'. Based on the predicted locations of expressed protein products and large changes in expression levels, 14 of the 90 genes were selected as candidate dental pulp stem cell markers, particularly in relation to their multipotency characteristics. This characterization of cell clones obtained from a single specimen of human dental pulp provided information regarding new candidate marker genes for multipotent dental pulp stem cells, which could facilitate efficient analysis or enrichment of multipotent stem cells.0 Comments 0 Shares 15 Views 0 Reviews -
2%. https://www.selleckchem.com/products/tvb-3664.html CONCLUSION In conclusion, we think that this study provides supplementary arguments that HOXB13 variants are involved in Pca. © 2020 Wiley Periodicals, Inc.AIMS Breast cancer is the most frequently occurring cancer in women. Lumpectomy followed by radiotherapy is suggested to be as effective as a total mastectomy. Radiation-induced dermatitis often occurs as a result of breast radiotherapy. Recent studies suggest that doxepin has promising anti-inflammatory properties. This study was undertaken to evaluate the effects of doxepin therapy on radiation dermatitis. METHODS A double-blind randomized clinical trial was launched from 2016 to 2017, with a total of 48 patients who had undergone breast-conserving surgery and received postoperative radiation therapy. Radiotherapy was applied 5 days per week for 5 weeks. Adverse dermatological effects were evaluated by a physician at the beginning of the fifth week of radiotherapy and the patients were then randomly assigned (11 ratio) to receive either doxepin (5%) or placebo cream for 7 days. RESULTS There were no significant differences in the dermatitis grade between doxepin and placebo groups at baseline (P > .5). The occurrence of acute dermatitis (grade 2 or higher) was significantly lower with the use of doxepin than with placebo (P ≤ .0001, Zα = 1.96 at 95% confidence interval). CONCLUSION Doxepin cream prevents dermatitis grade 2 or higher during post-operative breast irradiation. Doxepin cream is easy to use, affordable and prevents pain and irritation. © 2020 The British Pharmacological Society.ISSUE ADDRESSED This article reports the qualitative evaluation of "Artspace," an innovative clinical program combining creative arts with physical and mental health care for young women. The program, provided since 2004, comprises weekly visual arts sessions alongside a youth health clinic offering drop-in appointments with a nurse, GP and counsellor. METHODS A qualitative evaluation of Artspace was conducted between 2016 and 2017. RESULTS The evaluation showed that Artspace was particularly beneficial for those clients who had considerable exposure to social adversity and trauma, and were experiencing related serious health impacts. Artspace facilitated their recovery by enabling equitable access facilitation, social inclusion, creating a "holding" environment, and through the directly therapeutic benefits of artist-led arts processes. CONCLUSIONS Our study highlights the positive impact of artist-led programs such as Artspace. It also attests to the importance of long-term sustainability of services, to allow the time needed for young people to experience genuine and sustained recovery, and to reduce the otherwise likely disadvantages associated with mental and physical health problems, as they move into their adult lives. SO WHAT? Youth health researchers have been recommending arts programs at health services as a means of engaging young people in health care for over 15 years, however, it remains an underutilised approach in primary care settings. Our evaluation affirms the effectiveness of art programs for this, and also demonstrates that art programs can be a key contributor to recovery from the serious health impacts of adversity and trauma. © 2020 Australian Health Promotion Association.AIMS The urethral dysfunction produced by a rat model of peripheral neurogenic detrusor underactivity (DU) using pelvic nerve crush (PNC) injury was characterized and then tested with the administration of tadalafil, a phosphodiesterase type 5 (PDE 5) inhibitor. METHODS Ten days after producing PNC rats, awake cystometrograms (CMGs) and isovolumetric cystometrograms with urethral perfusion pressure (IC-UPP) measurements were performed. Also, in control rats, IC-UPP was recorded before and after intravenous atropine administration to determine if the reduction of bladder contraction pressure affects urethral relaxation during voiding. Then, CMG and IC-UPP measurements in PNC rats were recorded after intravenous administration of tadalafil. Lastly, real-time polymerase chain reaction was used to measure transcript levels of neuronal nitric oxide synthases (nNOS), endothelial nitric oxide synthases, and PDE 5 in urethral specimens from PNC and control rats. RESULTS PNC rats demonstrated the characteristics of DU in CMG. Also, PNC rats exhibited significant decreases in isovolumetric bladder contraction amplitudes and urethral relaxation. Atropine attenuated the amplitude of isovolumetric bladder contractions; however, atropine did not affect urethral relaxation in control rats. Tadalafil decreased postvoid residual and increased voiding efficiency without changing bladder contraction amplitude in PNC rats. Also, tadalafil improved the amplitude of urethral relaxation during bladder contraction in PNC rats. Urethral nNOS transcript levels were upregulated in PNC rats compared to control rats. CONCLUSIONS PNC rats revealed both DU and impaired urethral relaxation. PDE 5 inhibition in PNC rats enhanced urethral relaxation during voiding, resulting in improved voiding efficiency. Thus, urethral dysfunction could be a potential target for the treatment of inefficient voiding associated with neurogenic DU. © 2020 Wiley Periodicals, Inc.AIMS In the current climate of evidence-based health care, the aim of this meta-synthesis was to collect and systematically analyse data from primary qualitative studies on pelvic organ prolapse (POP), to identify patient-centered perspectives on the natural course of POP. Information acquired in this study may be useful for ongoing research towards the development of core outcome sets (COS) in pelvic floor disorders. METHODS A CHORUS Working Group performed a standardized search of three different databases (Medline, Embase, Scopus), from inception to October 2019. We selected qualitative studies on women's perspectives on POP that were published in the English language. Three reviewers independently evaluated the quality of eligible papers and highlighted recurrent themes based on patient perspectives. RESULTS Eighteen qualitative studies including a total of 497 patients were assessed in this analysis. Our study revealed five superordinate themes, recurrently encountered in qualitative studies on POP awareness of POP (6 studies), communication (9 studies), treatments (10 studies), effects on quality of life (6 studies), and self-image (3 studies).
2%. https://www.selleckchem.com/products/tvb-3664.html CONCLUSION In conclusion, we think that this study provides supplementary arguments that HOXB13 variants are involved in Pca. © 2020 Wiley Periodicals, Inc.AIMS Breast cancer is the most frequently occurring cancer in women. Lumpectomy followed by radiotherapy is suggested to be as effective as a total mastectomy. Radiation-induced dermatitis often occurs as a result of breast radiotherapy. Recent studies suggest that doxepin has promising anti-inflammatory properties. This study was undertaken to evaluate the effects of doxepin therapy on radiation dermatitis. METHODS A double-blind randomized clinical trial was launched from 2016 to 2017, with a total of 48 patients who had undergone breast-conserving surgery and received postoperative radiation therapy. Radiotherapy was applied 5 days per week for 5 weeks. Adverse dermatological effects were evaluated by a physician at the beginning of the fifth week of radiotherapy and the patients were then randomly assigned (11 ratio) to receive either doxepin (5%) or placebo cream for 7 days. RESULTS There were no significant differences in the dermatitis grade between doxepin and placebo groups at baseline (P > .5). The occurrence of acute dermatitis (grade 2 or higher) was significantly lower with the use of doxepin than with placebo (P ≤ .0001, Zα = 1.96 at 95% confidence interval). CONCLUSION Doxepin cream prevents dermatitis grade 2 or higher during post-operative breast irradiation. Doxepin cream is easy to use, affordable and prevents pain and irritation. © 2020 The British Pharmacological Society.ISSUE ADDRESSED This article reports the qualitative evaluation of "Artspace," an innovative clinical program combining creative arts with physical and mental health care for young women. The program, provided since 2004, comprises weekly visual arts sessions alongside a youth health clinic offering drop-in appointments with a nurse, GP and counsellor. METHODS A qualitative evaluation of Artspace was conducted between 2016 and 2017. RESULTS The evaluation showed that Artspace was particularly beneficial for those clients who had considerable exposure to social adversity and trauma, and were experiencing related serious health impacts. Artspace facilitated their recovery by enabling equitable access facilitation, social inclusion, creating a "holding" environment, and through the directly therapeutic benefits of artist-led arts processes. CONCLUSIONS Our study highlights the positive impact of artist-led programs such as Artspace. It also attests to the importance of long-term sustainability of services, to allow the time needed for young people to experience genuine and sustained recovery, and to reduce the otherwise likely disadvantages associated with mental and physical health problems, as they move into their adult lives. SO WHAT? Youth health researchers have been recommending arts programs at health services as a means of engaging young people in health care for over 15 years, however, it remains an underutilised approach in primary care settings. Our evaluation affirms the effectiveness of art programs for this, and also demonstrates that art programs can be a key contributor to recovery from the serious health impacts of adversity and trauma. © 2020 Australian Health Promotion Association.AIMS The urethral dysfunction produced by a rat model of peripheral neurogenic detrusor underactivity (DU) using pelvic nerve crush (PNC) injury was characterized and then tested with the administration of tadalafil, a phosphodiesterase type 5 (PDE 5) inhibitor. METHODS Ten days after producing PNC rats, awake cystometrograms (CMGs) and isovolumetric cystometrograms with urethral perfusion pressure (IC-UPP) measurements were performed. Also, in control rats, IC-UPP was recorded before and after intravenous atropine administration to determine if the reduction of bladder contraction pressure affects urethral relaxation during voiding. Then, CMG and IC-UPP measurements in PNC rats were recorded after intravenous administration of tadalafil. Lastly, real-time polymerase chain reaction was used to measure transcript levels of neuronal nitric oxide synthases (nNOS), endothelial nitric oxide synthases, and PDE 5 in urethral specimens from PNC and control rats. RESULTS PNC rats demonstrated the characteristics of DU in CMG. Also, PNC rats exhibited significant decreases in isovolumetric bladder contraction amplitudes and urethral relaxation. Atropine attenuated the amplitude of isovolumetric bladder contractions; however, atropine did not affect urethral relaxation in control rats. Tadalafil decreased postvoid residual and increased voiding efficiency without changing bladder contraction amplitude in PNC rats. Also, tadalafil improved the amplitude of urethral relaxation during bladder contraction in PNC rats. Urethral nNOS transcript levels were upregulated in PNC rats compared to control rats. CONCLUSIONS PNC rats revealed both DU and impaired urethral relaxation. PDE 5 inhibition in PNC rats enhanced urethral relaxation during voiding, resulting in improved voiding efficiency. Thus, urethral dysfunction could be a potential target for the treatment of inefficient voiding associated with neurogenic DU. © 2020 Wiley Periodicals, Inc.AIMS In the current climate of evidence-based health care, the aim of this meta-synthesis was to collect and systematically analyse data from primary qualitative studies on pelvic organ prolapse (POP), to identify patient-centered perspectives on the natural course of POP. Information acquired in this study may be useful for ongoing research towards the development of core outcome sets (COS) in pelvic floor disorders. METHODS A CHORUS Working Group performed a standardized search of three different databases (Medline, Embase, Scopus), from inception to October 2019. We selected qualitative studies on women's perspectives on POP that were published in the English language. Three reviewers independently evaluated the quality of eligible papers and highlighted recurrent themes based on patient perspectives. RESULTS Eighteen qualitative studies including a total of 497 patients were assessed in this analysis. Our study revealed five superordinate themes, recurrently encountered in qualitative studies on POP awareness of POP (6 studies), communication (9 studies), treatments (10 studies), effects on quality of life (6 studies), and self-image (3 studies).0 Comments 0 Shares 15 Views 0 Reviews -
© 2020 Société Française de Pharmacologie et de Thérapeutique.Vitamin C (VitC) is an essential vitamin that needs to be provided through exogenous sources. It is a potent anti-oxidant, and an essential cofactor for many enzymes including a group of enzymes that modulate epigenetic regulation of gene expression. Moreover, VitC has a significant influence on T-cell differentiation, and can directly interfere with T-cell signaling. Conventional CD4 and CD8 T cells express the αβ TCR and recognize peptide antigens in the context of ****presentation. The numerically small population of γδ T cells recognizes antigens in an ****independent manner. γδ T cells kill a broad variety of malignant cells, and because of their unique features, are interesting candidates for cancer immunotherapy. In this review, we summarize what is known about the influence of VitC on T-cell activation and differentiation with a special focus on γδ T cells. The known mechanisms of action of VitC on αβ T cells are discussed and extrapolated to the effects observed on γδ T-cell activation and differentiation. Overall, VitC enhances proliferation and effector functions of γδ T cells and thus may help to increase the efficacy of γδ T cells applied as cancer immunotherapy in adoptive cell transfer. ©2020 Society for Leukocyte Biology.AIM Tablets can be manipulated in several ways to obtain a fraction as the dose-a practice frequently seen in paediatric care due to lack of suitable formulations. Splitting tablets prior to fragment dispersion in a small volume of liquid is one such method. The objective of this study was to investigate the accuracy and precision of this method. METHODS Four different types of aspirin tablets (two dispersible, one conventional and one chewing) were split with a tablet splitter into half and quarter fragments. The fragments were dispersed in a medicine measure or an oral syringe. The amount recovered was determined by UHPLC analysis. RESULTS The largest quarter fragments ranged from 26.7% to 31.5% of the full tablet weight. Dispersing the fragment in an oral syringe, the amount recovered was greater than 90.8% of the fragment manipulated for all four tablet types, when rinsing was performed. Dispersing the fragment in a medicine measure, the amounts recovered spanned from 32.9% for the conventional tablets to 98.7% for one of the dispersible tablets. CONCLUSION Dispersion of half or quarter tablets directly in an oral syringe, but not a medicine measure, could give satisfactory recovery from fragments of all the investigated aspirin tablets. © 2020 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.Nowadays there are approximately 80 Anglophone journals that deal primarily with disaster risk reduction (DRR) and allied fields. This large array signals a sustained, if uneven, growth in DRR scholarship but also competition between the offerings of different publishers and institutions. The purpose of this article is first to summarise the development of academic publishing on DRR from its early beginnings to the present day. The paper then evaluates the current state of publishing in this field and discusses possible future trends. Next, it identifies some possible opportunities, challenges, expectations, and commitments for journal editors both within DRR and academia more broadly, including those that refer to changes in the use of terminology, the relentless increase in the number of papers submitted, the expansion and dangers of predatory journals, different peer review models, open access versus paywalls, citations and bibliography metrics, academic social networks, and copyright and distribution issues. This article is protected by copyright. All rights reserved.OBJECTIVES The present study explored how challenge and threat responses to stress relate to performance, anxiety, confidence, team identity and team characteristics (time spent in training and postgraduate experience) in a medical simulation-based team competition. METHODS The study was conducted during a national simulation-based training event for residents, the SIMCUP Italia 2018. The SIMCUP is a simulation competition in which teams of four compete in simulated medical emergency scenarios. Cross-sectional data were collected prior to the 3 days of the competition. Subjects included 95 participants on 24 teams. Before the competition on each day, participants completed brief self-report measures that assessed demands and resources (which underpin challenge and threat responses to stress), cognitive and somatic anxiety, self-confidence and team identification. Participants also reported time (hours) spent practising as a team and years of postgraduate experience. A team of referees judged each scenario forsources, and the interaction between the two. Higher levels of resources and lower demands were associated with better performance. © 2020 John Wiley & Sons Ltd and The Association for the Study of Medical Education.BACKGROUND Autosomal recessive mutations in the glucocerebrosidase gene, Beta-glucocerebrosidase 1 (GBA1), cause the lysosomal storage disorder Gaucher's disease. Heterozygous carriers of most GBA1 mutations have dramatically increased Parkinson's disease (PD) risk, but the mechanisms and cells affected remain unknown. Glucocerebrosidase expression is relatively enriched in astrocytes, yet the impact of its mutation in these cells has not yet been addressed. OBJECTIVES Emerging data supporting non-cell-autonomous mechanisms driving PD pathogenesis inspired the first characterization of GBA1-mutant astrocytes. In addition, we asked whether LRRK2, likewise linked to PD and enriched in astrocytes, intersected with GBA1 phenotypes. METHODS Using heterozygous and homozygous GBA1 D409V knockin mouse astrocytes, we conducted rigorous biochemical and image-based analyses of lysosomal function and morphology. We also examined basal and evoked cytokine response at the transcriptional and secretory levels. RESULTS The D409V knockin astrocytes manifested broad deficits in lysosomal morphology and function, as expected. This, however, is the first study to show dramatic defects in basal and TLR4-dependent cytokine production. Albeit to different extents, both the lysosomal dysfunction and inflammatory responses were normalized by inhibition of LRRK2 kinase activity, suggesting functional intracellular crosstalk between glucocerebrosidase and LRRK2 activities in astrocytes. CONCLUSIONS These data demonstrate novel pathologic effects of a GBA1 mutation on inflammatory responses in astrocytes, indicating the likelihood of broader immunologic changes in GBA-PD patients. Our findings support the involvement of non-cell-autonomous mechanisms contributing to the pathogenesis of GBA1-linked PD and identify new opportunities to correct these changes with pharmacological intervention. https://www.selleckchem.com/products/msdc-0160.html © 2020 International Parkinson and Movement Disorder Society. © 2020 International Parkinson and Movement Disorder Society.
© 2020 Société Française de Pharmacologie et de Thérapeutique.Vitamin C (VitC) is an essential vitamin that needs to be provided through exogenous sources. It is a potent anti-oxidant, and an essential cofactor for many enzymes including a group of enzymes that modulate epigenetic regulation of gene expression. Moreover, VitC has a significant influence on T-cell differentiation, and can directly interfere with T-cell signaling. Conventional CD4 and CD8 T cells express the αβ TCR and recognize peptide antigens in the context of MHC presentation. The numerically small population of γδ T cells recognizes antigens in an MHC-independent manner. γδ T cells kill a broad variety of malignant cells, and because of their unique features, are interesting candidates for cancer immunotherapy. In this review, we summarize what is known about the influence of VitC on T-cell activation and differentiation with a special focus on γδ T cells. The known mechanisms of action of VitC on αβ T cells are discussed and extrapolated to the effects observed on γδ T-cell activation and differentiation. Overall, VitC enhances proliferation and effector functions of γδ T cells and thus may help to increase the efficacy of γδ T cells applied as cancer immunotherapy in adoptive cell transfer. ©2020 Society for Leukocyte Biology.AIM Tablets can be manipulated in several ways to obtain a fraction as the dose-a practice frequently seen in paediatric care due to lack of suitable formulations. Splitting tablets prior to fragment dispersion in a small volume of liquid is one such method. The objective of this study was to investigate the accuracy and precision of this method. METHODS Four different types of aspirin tablets (two dispersible, one conventional and one chewing) were split with a tablet splitter into half and quarter fragments. The fragments were dispersed in a medicine measure or an oral syringe. The amount recovered was determined by UHPLC analysis. RESULTS The largest quarter fragments ranged from 26.7% to 31.5% of the full tablet weight. Dispersing the fragment in an oral syringe, the amount recovered was greater than 90.8% of the fragment manipulated for all four tablet types, when rinsing was performed. Dispersing the fragment in a medicine measure, the amounts recovered spanned from 32.9% for the conventional tablets to 98.7% for one of the dispersible tablets. CONCLUSION Dispersion of half or quarter tablets directly in an oral syringe, but not a medicine measure, could give satisfactory recovery from fragments of all the investigated aspirin tablets. © 2020 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.Nowadays there are approximately 80 Anglophone journals that deal primarily with disaster risk reduction (DRR) and allied fields. This large array signals a sustained, if uneven, growth in DRR scholarship but also competition between the offerings of different publishers and institutions. The purpose of this article is first to summarise the development of academic publishing on DRR from its early beginnings to the present day. The paper then evaluates the current state of publishing in this field and discusses possible future trends. Next, it identifies some possible opportunities, challenges, expectations, and commitments for journal editors both within DRR and academia more broadly, including those that refer to changes in the use of terminology, the relentless increase in the number of papers submitted, the expansion and dangers of predatory journals, different peer review models, open access versus paywalls, citations and bibliography metrics, academic social networks, and copyright and distribution issues. This article is protected by copyright. All rights reserved.OBJECTIVES The present study explored how challenge and threat responses to stress relate to performance, anxiety, confidence, team identity and team characteristics (time spent in training and postgraduate experience) in a medical simulation-based team competition. METHODS The study was conducted during a national simulation-based training event for residents, the SIMCUP Italia 2018. The SIMCUP is a simulation competition in which teams of four compete in simulated medical emergency scenarios. Cross-sectional data were collected prior to the 3 days of the competition. Subjects included 95 participants on 24 teams. Before the competition on each day, participants completed brief self-report measures that assessed demands and resources (which underpin challenge and threat responses to stress), cognitive and somatic anxiety, self-confidence and team identification. Participants also reported time (hours) spent practising as a team and years of postgraduate experience. A team of referees judged each scenario forsources, and the interaction between the two. Higher levels of resources and lower demands were associated with better performance. © 2020 John Wiley & Sons Ltd and The Association for the Study of Medical Education.BACKGROUND Autosomal recessive mutations in the glucocerebrosidase gene, Beta-glucocerebrosidase 1 (GBA1), cause the lysosomal storage disorder Gaucher's disease. Heterozygous carriers of most GBA1 mutations have dramatically increased Parkinson's disease (PD) risk, but the mechanisms and cells affected remain unknown. Glucocerebrosidase expression is relatively enriched in astrocytes, yet the impact of its mutation in these cells has not yet been addressed. OBJECTIVES Emerging data supporting non-cell-autonomous mechanisms driving PD pathogenesis inspired the first characterization of GBA1-mutant astrocytes. In addition, we asked whether LRRK2, likewise linked to PD and enriched in astrocytes, intersected with GBA1 phenotypes. METHODS Using heterozygous and homozygous GBA1 D409V knockin mouse astrocytes, we conducted rigorous biochemical and image-based analyses of lysosomal function and morphology. We also examined basal and evoked cytokine response at the transcriptional and secretory levels. RESULTS The D409V knockin astrocytes manifested broad deficits in lysosomal morphology and function, as expected. This, however, is the first study to show dramatic defects in basal and TLR4-dependent cytokine production. Albeit to different extents, both the lysosomal dysfunction and inflammatory responses were normalized by inhibition of LRRK2 kinase activity, suggesting functional intracellular crosstalk between glucocerebrosidase and LRRK2 activities in astrocytes. CONCLUSIONS These data demonstrate novel pathologic effects of a GBA1 mutation on inflammatory responses in astrocytes, indicating the likelihood of broader immunologic changes in GBA-PD patients. Our findings support the involvement of non-cell-autonomous mechanisms contributing to the pathogenesis of GBA1-linked PD and identify new opportunities to correct these changes with pharmacological intervention. https://www.selleckchem.com/products/msdc-0160.html © 2020 International Parkinson and Movement Disorder Society. © 2020 International Parkinson and Movement Disorder Society.0 Comments 0 Shares 15 Views 0 Reviews -
001) and the presence of necrosis (p = 0.021). In univariate survival analysis, we identified the following three novel morphological features associated with survival exophytic polypoid growth pattern, tumor density, and single mesothelium layered tubular structures. After adjustments, low nuclear grade (p less then 0.001) and presence of exophytic polypoid growth (p = 0.024) were associated with prolonged survival. These results may aid in estimating DMM prognosis. Flat urothelial lesions with atypia may pose significant diagnostic challenges. Given frequent increased proliferation rates in florid reactive urothelial atypia and limited studies on the interpretation of p53 stains in urothelium (following current standard guidelines for correlation with P53 mutation status), we sought to further study the discriminatory value of Ki-67 and p53 for florid reactive urothelial atypia versus urothelial carcinoma in situ (CIS). Bladder specimens diagnosed as reactive urothelial atypia (n=40) and CIS (n=40) were assessed by immunohistochemical staining with antibodies for Ki-67, p53, CD44, and CK20. Immunoreactivity was scored based on percent cells positive for Ki-67 and pattern of reactivity with p53 [aberrant diffuse strong positive or negative; normal patchy/wild type]. CD44 and CK20 reactivity patterns served as adjunctive internal validation controls for reactive urothelial atypia and CIS, as previously described. In reactive urothelial atypia, Ki-67 ranged from 0% to 90% 40%) showed focal expression in the non-neoplastic basal cell layer; 24 cases (60%) demonstrated no staining. In summary, Ki-67 has poor discriminatory value for reactive urothelial atypia versus CIS, and adds little to the classic CK20/CD44 immunophenotype. While p53 sensitivity for CIS is relatively low (30%) and interpretation as either wild type or negative may be challenging in a small subset of cases, strong and diffuse nuclear reactivity was 100% specific in the distinction from florid reactive urothelial atypia in this cohort. Diabetes mellitus (DM) is a highly prevalent chronic systemic disease, which may cause cognitive decline and degenerative change of the brain. Neuronal differentiation defects of neural stem cells (NSCs) played an important role in the development and progression of diabetes-associated cognitive decline (DACD), but the intrinsic pathological mechanism remains largely unclear. In the present study, we demonstrated that expression level of HDAC3 was upregulated in diabetic **** with reduced learning and memory abilities and in cultured NSCs after advanced glycation end products (AGEs) induction. In addition, AGEs interfered with normal differentiation of the cultured NSCs, and knocking down the expression of HDAC3 could partially attenuate the inhibitory effect of AGEs on NSCs differentiation. Findings in this study demonstrate that HDAC3 may serve as an experimental clue for revealing the pathogenesis of DACD. Electroacupuncture (EA), a traditional Chinese replacement therapy, is widely accepted to treat ischemic stroke. Increasing evidence show that autophagy is involved in the process of cerebral ischemia injury and the Wnt/GSK3β pathway, playing an important role in protecting central nervous system. In this study, rats were treated with EA prior to focal ischemia by middle cerebral artery occlusion (MCAO). Deficit score, infarct volumes and levels of autophagy markers, such as LC3I, LC3II and p62, were assessed with either PI3K inhibitor wortmannin or a GSK-3β inhibitor LiCl. Oxygen-glucose deprivation/re-oxygenation (OGD/R) was made in the primitive neuron in vitro, and was respectively treated with autophagy inhibitors 3-MA, LiCl, GSK3β siRNA, or mTOR inhibitor rapamycin. The results indicated that EA pretreatment increased the levels of autophagy marker LC3-II and reduced the levels of p62. Meanwhile, deficit outcome was improved, and infarct volumes were reduced by EA pretreatment. https://www.selleckchem.com/products/ory-1001-rg-6016.html Furthermore, the beneficial effects of EA pretreatment were reversed by wortmannin. LiCl and GSK3β siRNA can mimic the neuroprotective effects of EA pretreatment by downregulating autophagy, and increasing protein levels of p-mTOR, p-GSK3β and β-catenin in OGD/R neurons. However, the protective effects of GSK3β siRNA were blocked by rapamycin. These results suggest that EA pretreatment induces tolerance to cerebral ischemia by inhibiting autophagy via the Wnt pathway through the inhibition of GSK3β. BACKGROUND Nearly half of all pregnancies in the United States each year are unintended, with the highest rates observed among non-Hispanic black and Hispanic women. Little is known about whether variations in unintended pregnancy and contraceptive use across racial and ethnic groups persist among women Veteran VA-users who have more universal access than other populations to health care and contraceptive services. OBJECTIVES The objectives of this study were to identify history of unintended pregnancy and describe patterns of contraceptive use across racial and ethnic groups among women Veterans accessing VA primary care. STUDY DESIGN Cross-sectional data from a national random sample of women Veterans (n=2302) ages 18-44 who had accessed VA primary care in the previous 12 month were used to assess history of unintended pregnancy (pregnancies reported as either 'unwanted' or having occurred 'too soon'). Any contraceptive use at last sex (both prescription and non-prescription methods) and prescription contraery of patient-centered reproductive goals assessment and contraceptive counseling that can address knowledge gaps while respectfully considering individual patient preferences is needed to support women Veterans' decision-making and ensure equitable reproductive health services across VA. BACKGROUND A rapid increase in restrictive abortion legislation in the United States has sparked renewed interest in self-managed abortion as a response to clinic access barriers. Yet little is known about knowledge of, interest in, and experiences of self-managed medication abortion among patients who obtain abortion care in a clinic. OBJECTIVE (s) We examined patients' knowledge of, interest in, and experience with self-managed medication abortion before presenting to the clinic. We characterized the clinic- and person-level factors associated with these measures. Finally, we examined the reasons why patients express an interest in or consider self-management before attending the clinic. STUDY DESIGN We surveyed 1,502 abortion patients at three Texas clinics in McAllen, San Antonio, and Fort Worth. All individuals seeking abortion care who could complete the survey in English or Spanish were invited to participate in an anonymous survey conducted using iPads. The overall response rate was 90%. We examined the prevalence of four outcome variables, both overall, and separately by site 1) knowledge of self-managed medication abortion; 2) having considered self-managing using medications before attending the clinic; 3) interest in medication self-management as an alternative to accessing care at the clinic; and 4) having sought or tried any method of self-management before attending the clinic.
001) and the presence of necrosis (p = 0.021). In univariate survival analysis, we identified the following three novel morphological features associated with survival exophytic polypoid growth pattern, tumor density, and single mesothelium layered tubular structures. After adjustments, low nuclear grade (p less then 0.001) and presence of exophytic polypoid growth (p = 0.024) were associated with prolonged survival. These results may aid in estimating DMM prognosis. Flat urothelial lesions with atypia may pose significant diagnostic challenges. Given frequent increased proliferation rates in florid reactive urothelial atypia and limited studies on the interpretation of p53 stains in urothelium (following current standard guidelines for correlation with P53 mutation status), we sought to further study the discriminatory value of Ki-67 and p53 for florid reactive urothelial atypia versus urothelial carcinoma in situ (CIS). Bladder specimens diagnosed as reactive urothelial atypia (n=40) and CIS (n=40) were assessed by immunohistochemical staining with antibodies for Ki-67, p53, CD44, and CK20. Immunoreactivity was scored based on percent cells positive for Ki-67 and pattern of reactivity with p53 [aberrant diffuse strong positive or negative; normal patchy/wild type]. CD44 and CK20 reactivity patterns served as adjunctive internal validation controls for reactive urothelial atypia and CIS, as previously described. In reactive urothelial atypia, Ki-67 ranged from 0% to 90% 40%) showed focal expression in the non-neoplastic basal cell layer; 24 cases (60%) demonstrated no staining. In summary, Ki-67 has poor discriminatory value for reactive urothelial atypia versus CIS, and adds little to the classic CK20/CD44 immunophenotype. While p53 sensitivity for CIS is relatively low (30%) and interpretation as either wild type or negative may be challenging in a small subset of cases, strong and diffuse nuclear reactivity was 100% specific in the distinction from florid reactive urothelial atypia in this cohort. Diabetes mellitus (DM) is a highly prevalent chronic systemic disease, which may cause cognitive decline and degenerative change of the brain. Neuronal differentiation defects of neural stem cells (NSCs) played an important role in the development and progression of diabetes-associated cognitive decline (DACD), but the intrinsic pathological mechanism remains largely unclear. In the present study, we demonstrated that expression level of HDAC3 was upregulated in diabetic mice with reduced learning and memory abilities and in cultured NSCs after advanced glycation end products (AGEs) induction. In addition, AGEs interfered with normal differentiation of the cultured NSCs, and knocking down the expression of HDAC3 could partially attenuate the inhibitory effect of AGEs on NSCs differentiation. Findings in this study demonstrate that HDAC3 may serve as an experimental clue for revealing the pathogenesis of DACD. Electroacupuncture (EA), a traditional Chinese replacement therapy, is widely accepted to treat ischemic stroke. Increasing evidence show that autophagy is involved in the process of cerebral ischemia injury and the Wnt/GSK3β pathway, playing an important role in protecting central nervous system. In this study, rats were treated with EA prior to focal ischemia by middle cerebral artery occlusion (MCAO). Deficit score, infarct volumes and levels of autophagy markers, such as LC3I, LC3II and p62, were assessed with either PI3K inhibitor wortmannin or a GSK-3β inhibitor LiCl. Oxygen-glucose deprivation/re-oxygenation (OGD/R) was made in the primitive neuron in vitro, and was respectively treated with autophagy inhibitors 3-MA, LiCl, GSK3β siRNA, or mTOR inhibitor rapamycin. The results indicated that EA pretreatment increased the levels of autophagy marker LC3-II and reduced the levels of p62. Meanwhile, deficit outcome was improved, and infarct volumes were reduced by EA pretreatment. https://www.selleckchem.com/products/ory-1001-rg-6016.html Furthermore, the beneficial effects of EA pretreatment were reversed by wortmannin. LiCl and GSK3β siRNA can mimic the neuroprotective effects of EA pretreatment by downregulating autophagy, and increasing protein levels of p-mTOR, p-GSK3β and β-catenin in OGD/R neurons. However, the protective effects of GSK3β siRNA were blocked by rapamycin. These results suggest that EA pretreatment induces tolerance to cerebral ischemia by inhibiting autophagy via the Wnt pathway through the inhibition of GSK3β. BACKGROUND Nearly half of all pregnancies in the United States each year are unintended, with the highest rates observed among non-Hispanic black and Hispanic women. Little is known about whether variations in unintended pregnancy and contraceptive use across racial and ethnic groups persist among women Veteran VA-users who have more universal access than other populations to health care and contraceptive services. OBJECTIVES The objectives of this study were to identify history of unintended pregnancy and describe patterns of contraceptive use across racial and ethnic groups among women Veterans accessing VA primary care. STUDY DESIGN Cross-sectional data from a national random sample of women Veterans (n=2302) ages 18-44 who had accessed VA primary care in the previous 12 month were used to assess history of unintended pregnancy (pregnancies reported as either 'unwanted' or having occurred 'too soon'). Any contraceptive use at last sex (both prescription and non-prescription methods) and prescription contraery of patient-centered reproductive goals assessment and contraceptive counseling that can address knowledge gaps while respectfully considering individual patient preferences is needed to support women Veterans' decision-making and ensure equitable reproductive health services across VA. BACKGROUND A rapid increase in restrictive abortion legislation in the United States has sparked renewed interest in self-managed abortion as a response to clinic access barriers. Yet little is known about knowledge of, interest in, and experiences of self-managed medication abortion among patients who obtain abortion care in a clinic. OBJECTIVE (s) We examined patients' knowledge of, interest in, and experience with self-managed medication abortion before presenting to the clinic. We characterized the clinic- and person-level factors associated with these measures. Finally, we examined the reasons why patients express an interest in or consider self-management before attending the clinic. STUDY DESIGN We surveyed 1,502 abortion patients at three Texas clinics in McAllen, San Antonio, and Fort Worth. All individuals seeking abortion care who could complete the survey in English or Spanish were invited to participate in an anonymous survey conducted using iPads. The overall response rate was 90%. We examined the prevalence of four outcome variables, both overall, and separately by site 1) knowledge of self-managed medication abortion; 2) having considered self-managing using medications before attending the clinic; 3) interest in medication self-management as an alternative to accessing care at the clinic; and 4) having sought or tried any method of self-management before attending the clinic.0 Comments 0 Shares 15 Views 0 Reviews -
BACKGROUND Our earlier Google Trend (GT) Analytics study reported that the worldwide human population severely subject to four seasonal (sensitive) comorbid lifestyle diseases (SCLD) such as asthma, obesity, hypertension and fibrosis. The human population subject to seasonal variability in these four diseases activity referred as "severe seasonal sensitive population". In India, the estimated burden of these four seasonal diseases is more than 350 million as on the year 2018. It is a growing crisis for India with a projected disease burden of 500 million in the year 2025. This study was aimed to decipher the genuine SCLD seasonal trends in the entire Indian population using GT and validate these trends in Indian climatic zones. METHODS GT is used to study the temporal trends in web search using weekly Relative Search Volume (RSV) for the period 2004 to 2017. The relative search volume (RSV) of the four-severe seasonal comorbid diseases namely Asthma, Hypertension, Obesity and Fibrosis were collected with and zones. CONCLUSIONS The clinical outcome arise out of these observations could be of immense significance in handling the major chronic life style diseases asthma, hypertension, obesity and fibrosis. The possible strong comorbid relationship among asthma, hypertension, obesity and fibrosis may be useful to segregate Indian seasonal sensitive population. In disease activity-based chronotherapy, the search interest of segment of the population with access to Internet may be used as an indicator for public health sectors in the early detection of SCLD from a specific country or a region. As this disease population could be highly subject to the adverse effect of seasons in addition to life style and other environmental factors. Our study necessitates that these Indian populations need special attention from the Indian health care sectors.BACKGROUND Currently used performance measures for discrimination were not informative to determine the clinical benefit of predictor variables. The purpose was to evaluate if a former relevant predictor, kinesiophobia, remained clinically relevant to predict chronic occupational low **** pain (LBP) in the light of a novel discriminative performance measure, Decision Curve Analysis (DCA), using the Net Benefit (NB). METHODS Prospective cohort data (n = 170) of two merged randomized trials with workers with LBP on sickleave, treated with Usual Care (UC) were used for the analyses. An existing prediction model for chronic LBP with the variables 'a clinically relevant change in pain intensity and disability status in the first 3 months', 'baseline measured pain intensity' and 'kinesiophobia' was compared with the same model without the variable 'kinesiophobia' using the NB and DCA. RESULTS Both prediction models showed an equal performance according to the DCA and NB. Between 10 and 95% probability thresholds of chronic LBP risk, both models were of clinically benefit. There were virtually no differences between both models in the improved classification of true positive (TP) patients. CONCLUSIONS This study showed that the variable kinesiophobia, which was originally included in a prediction model for chronic LBP, was not informative to predict chronic LBP by using DCA. DCA and NB have to be used more often to develop clinically beneficial prediction models in workers because they are more sensitive to evaluate the discriminate ability of prediction models.BACKGROUND The effectiveness of female condoms for preventing HIV and sexually transmitted infections (STIs) remains inconclusive. We examined the effects of female condoms on the acquisition of HIV and STIs. METHODS We searched four databases, two trial registries, and reference lists of relevant publications in October 2018 and updated our search in February 2020. We screened search output, evaluated study eligibility, and extracted data in duplicate; resolving differences through discussion. We calculated the effective sample size of cluster randomised trials using an intra-cluster correlation coefficient of 0·03. Data from similar studies were combined in a meta-analysis. We performed a non-inferiority analysis of new condoms relative to marketed ones using a non-inferiority margin of 3%. We assessed the certainty of evidence using GRADE. RESULTS We included fifteen studies of 6921 women. We found that polyurethane female condoms (FC1) plus male condoms may be as effective as male condoms only in reducing HIV acquisition (1 trial, n = 149 women, RR 0.07, 95%CI 0.00-1.38; low-certainty evidence). However, the use of FC1 plus male condoms is superior to male condoms alone in reducing the acquisition of gonorrhoea (2 trials, n = 790, RR 0.59, 95%CI 0.41-0.86; high-certainty evidence) and chlamydia (2 trials, n = 790, RR 0.67, 95%CI 0.47-0.94; high-certainty evidence). Adverse events and failure rates of FC1 were very low and decreased during follow up. Although the functionality of newer female condoms (Woman's, Cupid, Pheonurse, Velvet, and Reddy) may be non-inferior to FC2, there were no available studies assessing their efficacy in preventing HIV and STIs. CONCLUSION The use of female plus male condoms is more effective than use of male condoms only in preventing STIs and may be as effective as the male condom only in preventing HIV. There is a need for well conducted studies assessing the effects of newer female condoms on HIV and STIs. PROSPERO REGISTRATION NUMBER CRD42018090710.BACKGROUND Dissociated responses (DR) are phenomena in which some tumors shrink, whereas others progress during treatment of patients with cancer. The purpose of the present study was to evaluate the frequency and prognosis of DR in non-small cell lung cancer (NSCLC) patients treated with anti-programmed cell death-1/ligand 1 (anti-PD-1/L1) inhibitors. METHODS This retrospective study included NSCLC patients who received anti-PD-1/L1 inhibitor as second- or later-line treatment. We excluded patients without radiological evaluation. In patients who showed progressive disease (PD) according to the RECIST 1.1 at the initial CT evaluation, we evaluated all measurable lesions in each organ to identify DR independently of RECIST 1.1. We defined DR as a disease with some shrinking lesions as well as growing or emerging new lesions. https://www.selleckchem.com/products/kpt-8602.html Cases not classified as DR were defined as 'true PD'. Overall survival was compared between patients with DR and those with true PD using Cox proportional hazards models. RESULTS The present study included 62 NSCLC patients aged 27-82 years (median 65 years).
BACKGROUND Our earlier Google Trend (GT) Analytics study reported that the worldwide human population severely subject to four seasonal (sensitive) comorbid lifestyle diseases (SCLD) such as asthma, obesity, hypertension and fibrosis. The human population subject to seasonal variability in these four diseases activity referred as "severe seasonal sensitive population". In India, the estimated burden of these four seasonal diseases is more than 350 million as on the year 2018. It is a growing crisis for India with a projected disease burden of 500 million in the year 2025. This study was aimed to decipher the genuine SCLD seasonal trends in the entire Indian population using GT and validate these trends in Indian climatic zones. METHODS GT is used to study the temporal trends in web search using weekly Relative Search Volume (RSV) for the period 2004 to 2017. The relative search volume (RSV) of the four-severe seasonal comorbid diseases namely Asthma, Hypertension, Obesity and Fibrosis were collected with and zones. CONCLUSIONS The clinical outcome arise out of these observations could be of immense significance in handling the major chronic life style diseases asthma, hypertension, obesity and fibrosis. The possible strong comorbid relationship among asthma, hypertension, obesity and fibrosis may be useful to segregate Indian seasonal sensitive population. In disease activity-based chronotherapy, the search interest of segment of the population with access to Internet may be used as an indicator for public health sectors in the early detection of SCLD from a specific country or a region. As this disease population could be highly subject to the adverse effect of seasons in addition to life style and other environmental factors. Our study necessitates that these Indian populations need special attention from the Indian health care sectors.BACKGROUND Currently used performance measures for discrimination were not informative to determine the clinical benefit of predictor variables. The purpose was to evaluate if a former relevant predictor, kinesiophobia, remained clinically relevant to predict chronic occupational low back pain (LBP) in the light of a novel discriminative performance measure, Decision Curve Analysis (DCA), using the Net Benefit (NB). METHODS Prospective cohort data (n = 170) of two merged randomized trials with workers with LBP on sickleave, treated with Usual Care (UC) were used for the analyses. An existing prediction model for chronic LBP with the variables 'a clinically relevant change in pain intensity and disability status in the first 3 months', 'baseline measured pain intensity' and 'kinesiophobia' was compared with the same model without the variable 'kinesiophobia' using the NB and DCA. RESULTS Both prediction models showed an equal performance according to the DCA and NB. Between 10 and 95% probability thresholds of chronic LBP risk, both models were of clinically benefit. There were virtually no differences between both models in the improved classification of true positive (TP) patients. CONCLUSIONS This study showed that the variable kinesiophobia, which was originally included in a prediction model for chronic LBP, was not informative to predict chronic LBP by using DCA. DCA and NB have to be used more often to develop clinically beneficial prediction models in workers because they are more sensitive to evaluate the discriminate ability of prediction models.BACKGROUND The effectiveness of female condoms for preventing HIV and sexually transmitted infections (STIs) remains inconclusive. We examined the effects of female condoms on the acquisition of HIV and STIs. METHODS We searched four databases, two trial registries, and reference lists of relevant publications in October 2018 and updated our search in February 2020. We screened search output, evaluated study eligibility, and extracted data in duplicate; resolving differences through discussion. We calculated the effective sample size of cluster randomised trials using an intra-cluster correlation coefficient of 0·03. Data from similar studies were combined in a meta-analysis. We performed a non-inferiority analysis of new condoms relative to marketed ones using a non-inferiority margin of 3%. We assessed the certainty of evidence using GRADE. RESULTS We included fifteen studies of 6921 women. We found that polyurethane female condoms (FC1) plus male condoms may be as effective as male condoms only in reducing HIV acquisition (1 trial, n = 149 women, RR 0.07, 95%CI 0.00-1.38; low-certainty evidence). However, the use of FC1 plus male condoms is superior to male condoms alone in reducing the acquisition of gonorrhoea (2 trials, n = 790, RR 0.59, 95%CI 0.41-0.86; high-certainty evidence) and chlamydia (2 trials, n = 790, RR 0.67, 95%CI 0.47-0.94; high-certainty evidence). Adverse events and failure rates of FC1 were very low and decreased during follow up. Although the functionality of newer female condoms (Woman's, Cupid, Pheonurse, Velvet, and Reddy) may be non-inferior to FC2, there were no available studies assessing their efficacy in preventing HIV and STIs. CONCLUSION The use of female plus male condoms is more effective than use of male condoms only in preventing STIs and may be as effective as the male condom only in preventing HIV. There is a need for well conducted studies assessing the effects of newer female condoms on HIV and STIs. PROSPERO REGISTRATION NUMBER CRD42018090710.BACKGROUND Dissociated responses (DR) are phenomena in which some tumors shrink, whereas others progress during treatment of patients with cancer. The purpose of the present study was to evaluate the frequency and prognosis of DR in non-small cell lung cancer (NSCLC) patients treated with anti-programmed cell death-1/ligand 1 (anti-PD-1/L1) inhibitors. METHODS This retrospective study included NSCLC patients who received anti-PD-1/L1 inhibitor as second- or later-line treatment. We excluded patients without radiological evaluation. In patients who showed progressive disease (PD) according to the RECIST 1.1 at the initial CT evaluation, we evaluated all measurable lesions in each organ to identify DR independently of RECIST 1.1. We defined DR as a disease with some shrinking lesions as well as growing or emerging new lesions. https://www.selleckchem.com/products/kpt-8602.html Cases not classified as DR were defined as 'true PD'. Overall survival was compared between patients with DR and those with true PD using Cox proportional hazards models. RESULTS The present study included 62 NSCLC patients aged 27-82 years (median 65 years).0 Comments 0 Shares 15 Views 0 Reviews
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