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Bioinformatics prediction and Luciferase assay demonstrated that circRNA_009934 served as a ceRNA of miR-5107 and regulated its downstream TRAF6 expression.
We first demonstrated that circRNA_009934 expression was increased in osteoclasts, which promoted osteoclastogenesis by serving as a ceRNA of miR-5107 and regulated the expression of TRAF6.
We first demonstrated that circRNA_009934 expression was increased in osteoclasts, which promoted osteoclastogenesis by serving as a ceRNA of miR-5107 and regulated the expression of TRAF6.Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "MiR-20a regulates fibroblast-like synoviocyte proliferation and apoptosis in rheumatoid arthritis, by X.-J. Wei, X.-W. Li, J.-L. Lu, Z.-X. Long, J.-Q. Liang, S.-B. Wei, C.-X. Lu, W.-Z. Lu, published in Eur Rev Med Pharmacol Sci 2017; 21 (17) 3886-3893-PMID 28975975" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https//www.europeanreview.org/article/13351.Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "MiR-155 regulates lymphoma cell proliferation and apoptosis through targeting SOCS3/JAK-STAT3 signaling pathway, by X.-D. Li, X.-M. Li, J.-W. **, X.-C. Sun, published in Eur Rev Med Pharmacol Sci 2017; 21 (22) 5153-5159-DOI 10.26355/eurrev_201711_13832-PMID 29228427" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https//www.europeanreview.org/article/13832.Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Knockdown of long noncoding RNA linc-ITGB1 suppresses migration, invasion of hepatocellular carcinoma via regulating ZEB1, by W.-W. Yu, K. Wang, G.-J. Liao, published in Eur Rev Med Pharmacol Sci 2017; 21 (22) 5089-5095-DOI 10.26355/eurrev_201711_13823 -PMID 29228420" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https//www.europeanreview.org/article/13823.Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "The effect of miR-224 down-regulation on SW80 cell proliferation and apoptosis and weakening of ADM drug resistance, by C.-Q. Liang, Y.-M. Fu, Z.-Y. Liu, B.-R. Xing, Y. Jin, J.-L. Huang, published in Eur Rev Med Pharmacol Sci 2017; 21 (21) 5008-5016-PMID 29164556" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https//www.europeanreview.org/article/13747.Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Targeting of GSK-3β by miR-214 to facilitate gastric cancer cell proliferation and decrease of cell apoptosis, by H.-L. Li, S. Liang, J.-H. https://www.selleckchem.com/products/cct241533-hydrochloride.html Cui, G.-Y. Han, published in Eur Rev Med Pharmacol Sci 2018; 22 (1) 127-134-DOI 10.26355/eurrev_201801_14109-PMID 29364479" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https//www.europeanreview.org/article/14109.Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Effects of miR-214 on cervical cancer cell proliferation, apoptosis and invasion via modulating PI3K/AKT/mTOR signal pathway, by F. Wang, W.-H. Tan, W. Liu, Y.-X. Jin, D.-D. Dong, X.-J. Zhao, Q. Liu, published in Eur Rev Med Pharmacol Sci 2018; 22 (7) 1891-1898-DOI 10.26355/eurrev_201804_14711-PMID 29687840" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https//www.europeanreview.org/article/14711.Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Long noncoding RNA CASC15 is upregulated in glioma and facilitates cell proliferation and metastasis via targeting miR-130b-3p, by Y. Xie, Y. Cheng, published in Eur Rev Med Pharmacol Sci 2019; 23 (17) 7475-7481-DOI 10.26355/eurrev_201909_18857-PMID 31539135" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https//www.europeanreview.org/article/18857.Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Long non-coding RNA PVT1 functions as an oncogene in ovarian cancer via upregulating SOX2, by M.-F. Zou, J. ****, Q.-Y. Wu, C.-X. Zhang, published in Eur Rev Med Pharmacol Sci 2018; 22 (21) 7183-7188-DOI 10.26355/eurrev_201811_16251-PMID 30468460" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https//www.europeanreview.org/article/16251.Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "MiR-100 up-regulation enhanced cell autophagy and apoptosis induced by cisplatin in osteosarcoma by targeting mTOR, by Z. Yu, N. Li, K. Jiang, N. Zhang, L.-L. Yao, published in Eur Rev Med Pharmacol Sci 2018; 22 (18) 5867-5873-DOI 10.26355/eurrev_201809_15913 -PMID 30280766" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https//www.europeanreview.org/article/15913.Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "LncRNA LUCAT1 promotes rowth, migration, and invasion of oral squamous cell carcinoma by upregulating PCNA, by Y. Kong, Y. Feng, Y.-Y. Xiao, S.-C. Liu, X.-G. Li, Q.-L. Yang, W.-H. Chu, J.-G. Liu, published in Eur Rev Med Pharmacol Sci 2019; 23 (11) 4770-4776- DOI 10.26355/eurrev_201906_18059-PMID 31210306" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https//www.europeanreview.org/article/18059.
Bioinformatics prediction and Luciferase assay demonstrated that circRNA_009934 served as a ceRNA of miR-5107 and regulated its downstream TRAF6 expression. We first demonstrated that circRNA_009934 expression was increased in osteoclasts, which promoted osteoclastogenesis by serving as a ceRNA of miR-5107 and regulated the expression of TRAF6. We first demonstrated that circRNA_009934 expression was increased in osteoclasts, which promoted osteoclastogenesis by serving as a ceRNA of miR-5107 and regulated the expression of TRAF6.Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "MiR-20a regulates fibroblast-like synoviocyte proliferation and apoptosis in rheumatoid arthritis, by X.-J. Wei, X.-W. Li, J.-L. Lu, Z.-X. Long, J.-Q. Liang, S.-B. Wei, C.-X. Lu, W.-Z. Lu, published in Eur Rev Med Pharmacol Sci 2017; 21 (17) 3886-3893-PMID 28975975" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https//www.europeanreview.org/article/13351.Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "MiR-155 regulates lymphoma cell proliferation and apoptosis through targeting SOCS3/JAK-STAT3 signaling pathway, by X.-D. Li, X.-M. Li, J.-W. Gu, X.-C. Sun, published in Eur Rev Med Pharmacol Sci 2017; 21 (22) 5153-5159-DOI 10.26355/eurrev_201711_13832-PMID 29228427" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https//www.europeanreview.org/article/13832.Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Knockdown of long noncoding RNA linc-ITGB1 suppresses migration, invasion of hepatocellular carcinoma via regulating ZEB1, by W.-W. Yu, K. Wang, G.-J. Liao, published in Eur Rev Med Pharmacol Sci 2017; 21 (22) 5089-5095-DOI 10.26355/eurrev_201711_13823 -PMID 29228420" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https//www.europeanreview.org/article/13823.Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "The effect of miR-224 down-regulation on SW80 cell proliferation and apoptosis and weakening of ADM drug resistance, by C.-Q. Liang, Y.-M. Fu, Z.-Y. Liu, B.-R. Xing, Y. Jin, J.-L. Huang, published in Eur Rev Med Pharmacol Sci 2017; 21 (21) 5008-5016-PMID 29164556" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https//www.europeanreview.org/article/13747.Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Targeting of GSK-3β by miR-214 to facilitate gastric cancer cell proliferation and decrease of cell apoptosis, by H.-L. Li, S. Liang, J.-H. https://www.selleckchem.com/products/cct241533-hydrochloride.html Cui, G.-Y. Han, published in Eur Rev Med Pharmacol Sci 2018; 22 (1) 127-134-DOI 10.26355/eurrev_201801_14109-PMID 29364479" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https//www.europeanreview.org/article/14109.Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Effects of miR-214 on cervical cancer cell proliferation, apoptosis and invasion via modulating PI3K/AKT/mTOR signal pathway, by F. Wang, W.-H. Tan, W. Liu, Y.-X. Jin, D.-D. Dong, X.-J. Zhao, Q. Liu, published in Eur Rev Med Pharmacol Sci 2018; 22 (7) 1891-1898-DOI 10.26355/eurrev_201804_14711-PMID 29687840" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https//www.europeanreview.org/article/14711.Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Long noncoding RNA CASC15 is upregulated in glioma and facilitates cell proliferation and metastasis via targeting miR-130b-3p, by Y. Xie, Y. Cheng, published in Eur Rev Med Pharmacol Sci 2019; 23 (17) 7475-7481-DOI 10.26355/eurrev_201909_18857-PMID 31539135" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https//www.europeanreview.org/article/18857.Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Long non-coding RNA PVT1 functions as an oncogene in ovarian cancer via upregulating SOX2, by M.-F. Zou, J. Ling, Q.-Y. Wu, C.-X. Zhang, published in Eur Rev Med Pharmacol Sci 2018; 22 (21) 7183-7188-DOI 10.26355/eurrev_201811_16251-PMID 30468460" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https//www.europeanreview.org/article/16251.Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "MiR-100 up-regulation enhanced cell autophagy and apoptosis induced by cisplatin in osteosarcoma by targeting mTOR, by Z. Yu, N. Li, K. Jiang, N. Zhang, L.-L. Yao, published in Eur Rev Med Pharmacol Sci 2018; 22 (18) 5867-5873-DOI 10.26355/eurrev_201809_15913 -PMID 30280766" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https//www.europeanreview.org/article/15913.Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "LncRNA LUCAT1 promotes rowth, migration, and invasion of oral squamous cell carcinoma by upregulating PCNA, by Y. Kong, Y. Feng, Y.-Y. Xiao, S.-C. Liu, X.-G. Li, Q.-L. Yang, W.-H. Chu, J.-G. Liu, published in Eur Rev Med Pharmacol Sci 2019; 23 (11) 4770-4776- DOI 10.26355/eurrev_201906_18059-PMID 31210306" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https//www.europeanreview.org/article/18059.0 Comentários 0 Compartilhamentos 185 Visualizações 0 AnteriorFaça Login para curtir, compartilhar e comentar! -
The characterization of mutational processes in terms of their signatures of activity relies mostly on the assumption that mutations in a given cancer genome are independent of one another. Recently, it was discovered that certain segments of mutations, termed processive groups, occur on the same DNA strand and are generated by a single process or signature. Here we provide a first probabilistic model of mutational signatures that accounts for their observed stickiness and strand coordination. The model conditions on the observed strand for each mutation and allows the same signature to generate a run of mutations. It can both use known signatures or learn new ones. We show that this model provides a more accurate description of the properties of mutagenic processes than independent-mutation achieving substantially higher likelihood on held-out data. https://www.selleckchem.com/products/namodenoson-cf-102.html We apply this model to characterize the processivity of mutagenic processes across multiple types of cancer. Cold shock proteins (Csps) are small and highly conserved proteins that have target RNA- and DNA-binding activities. Csps play roles in different cellular processes and show functional redundancy. Ralstonia solanacearum, the agent of bacterial wilt, has 4 or 5 Csps based on genome analysis. However, the functions of all Csps in R. solanacearum remain unclear. According to phylogenetic analysis, the Csps from R. solanacearum are clustered into a group with CspD from E. coli. Here, we studied the role of CspD3, which was closer to CspD of E. coli in the phylogenetic tree. A cspD3 deletion strain was constructed to assess its effect on the phenotype of R. solanacearum, including growth, biofilm formation, motility, and virulence. The results showed that cspD3 of R. solanacearum was not necessary for normal growth, cold-shock adaptation, or biofilm formation. However, deletion of cspD3 in R. solanacearum CQPS-1 led to increased swimming motility, and the mean diameters of swimming haloes produced by the ΔcspD3 mutant were 1.3-fold larger than those produced by wild-type strain and 1.2-fold larger than those produced by the complemented strain. More importantly, the virulence of the cspD3 deletion mutant on susceptible tobacco plants was significantly attenuated compared to the wild-type strain. At 20 days after inoculation, the disease index of the ΔcspD3 mutant was 2.27, which was reduced by 1.6-fold relative to the wild-type strain. To assess the molecular response influenced by cspD3, the expressions of the main motility-associated genes and virulence-associated genes including flgM, fliA, pehS, pehR, hrpG, xpsR, and prhI in R. solanacearum were measured. The results showed that the expressions of hrpG, xpsR, and prhI were significantly decreased in cspD3 deletion mutant. Collectively, our findings showed that Csps are involved in the regulation of motility and virulence in R. solanacearum. The study explored whether target detection in a five-character string depends on whether a letter or a non-letter was presented, as a predesignated target. Skilled readers had to identify a single letter or non-letter in a five-character string, randomly composed of letters and non-letters. It was found that an analytic processing strategy is automatically elicited if participants were instructed to detect a letter target. In this instance, a linear model best explained the RT variance for letters with increasing RTs from left to right, suggesting a serial item-by-item reading-specific strategy comparable to alphabetic reading. For non-letters, in contrast, a symmetrical U-shaped function best explained the RT variance, suggesting a symmetrical scanning-out from the central to the terminal positions of the string. Since the design precludes orthographic and semantic influences, it can be concluded that a reading-specific strategy for alphabetic processing is automatically activated if the string is scanned for a letter-target. Thus, the pre-designated target triggers the strategy for processing the string and determines related position effects. The results suggest that effects from earlier studies, which showed an analytic processing preference for isolated letters (APPLE) in recognition tasks, as a consequence of literacy acquisition, generalize to the processing of letters in strings. Microorganism-derived dissolved organic nitrogen (mDON) represents a significant and inevitable portion of dissolved organic nitrogen (DON) in the wastewater biotreatment processes. In the existing method, mDON concentrations are indirectly measured by the values of DON concentrations from the reactors with DON-free influent. However, this becomes problematic when influent contains DON. Especially when the real wastewater is involved, the paucity of the direct methods to quantitatively measure mDON is a major barrier to further research. This limitation is due to the difficulty of segregating mDON from the other nitrogenous organics, e.g., influent DON. In this study, we propose the ASM-mDON model based on ASM #1, which incorporates the production and consumption of mDON in the activated sludge processes to predict the mDON concentrations. In four independent lab-scale tests, our model was established and calibrated to obtain the accurate values of mDON (R2 = 0.929, p less then 0.05), and the validity and applicability of the model were successfully examined by comparing the simulated and measured data. Moreover, the universality of the ASM-mDON model was further confirmed by simulating mDON production in a full-scale wastewater treatment plant. A reasonable prediction of mDON formation was shown in a full-scale test (1.98 ± 0.71 mg/L in June and 1.51 ± 0.54 mg/L in July) and is indirectly supported by an algal bioassay (p less then 0.05, t-test). This study provides a useful approach to the efficient and accurate evaluation of mDON formation, which will improve current strategies designed to minimize the effluent mDON in wastewater bioprocesses. Using persulfate (PS) oxidation to remove the persistent perfluorooctanoic acid (PFOA) in water typically requires an elevated temperature or an extended reaction time. Under relatively ambient temperatures (15-45 °C), feasibility of employing PS with iron-modified activated carbon (AC) for PFOA oxidation was evaluated. With presence of Fe/AC in PS oxidation, 61.7% of PFOA was decomposed to fluoride ions and intermediates of short-chain perfluorinated carboxylic acids (PFCAs) with a 41.9% defluorination efficiency at 25 °C after 10 h. Adsorption of PFOA onto Fe/AC can be regarded as a pre-concentration step prior to subsequent oxidation of PFOA. Fe/AC not only removes PFOA through adsorption, but also activates PS to form sulfate radicals that accelerate the decomposition and mineralization of PFOA. With Fe/AC in the PS system, activation energies (Ea) of PFOA removal and defluorination were significantly reduced from 66.8 to 13.2 and 97.3 to 14.5 kJ/mol, respectively. It implies that PFOA degradation and defluorination could proceed at a lower reaction temperature within a shorter reaction time.
The characterization of mutational processes in terms of their signatures of activity relies mostly on the assumption that mutations in a given cancer genome are independent of one another. Recently, it was discovered that certain segments of mutations, termed processive groups, occur on the same DNA strand and are generated by a single process or signature. Here we provide a first probabilistic model of mutational signatures that accounts for their observed stickiness and strand coordination. The model conditions on the observed strand for each mutation and allows the same signature to generate a run of mutations. It can both use known signatures or learn new ones. We show that this model provides a more accurate description of the properties of mutagenic processes than independent-mutation achieving substantially higher likelihood on held-out data. https://www.selleckchem.com/products/namodenoson-cf-102.html We apply this model to characterize the processivity of mutagenic processes across multiple types of cancer. Cold shock proteins (Csps) are small and highly conserved proteins that have target RNA- and DNA-binding activities. Csps play roles in different cellular processes and show functional redundancy. Ralstonia solanacearum, the agent of bacterial wilt, has 4 or 5 Csps based on genome analysis. However, the functions of all Csps in R. solanacearum remain unclear. According to phylogenetic analysis, the Csps from R. solanacearum are clustered into a group with CspD from E. coli. Here, we studied the role of CspD3, which was closer to CspD of E. coli in the phylogenetic tree. A cspD3 deletion strain was constructed to assess its effect on the phenotype of R. solanacearum, including growth, biofilm formation, motility, and virulence. The results showed that cspD3 of R. solanacearum was not necessary for normal growth, cold-shock adaptation, or biofilm formation. However, deletion of cspD3 in R. solanacearum CQPS-1 led to increased swimming motility, and the mean diameters of swimming haloes produced by the ΔcspD3 mutant were 1.3-fold larger than those produced by wild-type strain and 1.2-fold larger than those produced by the complemented strain. More importantly, the virulence of the cspD3 deletion mutant on susceptible tobacco plants was significantly attenuated compared to the wild-type strain. At 20 days after inoculation, the disease index of the ΔcspD3 mutant was 2.27, which was reduced by 1.6-fold relative to the wild-type strain. To assess the molecular response influenced by cspD3, the expressions of the main motility-associated genes and virulence-associated genes including flgM, fliA, pehS, pehR, hrpG, xpsR, and prhI in R. solanacearum were measured. The results showed that the expressions of hrpG, xpsR, and prhI were significantly decreased in cspD3 deletion mutant. Collectively, our findings showed that Csps are involved in the regulation of motility and virulence in R. solanacearum. The study explored whether target detection in a five-character string depends on whether a letter or a non-letter was presented, as a predesignated target. Skilled readers had to identify a single letter or non-letter in a five-character string, randomly composed of letters and non-letters. It was found that an analytic processing strategy is automatically elicited if participants were instructed to detect a letter target. In this instance, a linear model best explained the RT variance for letters with increasing RTs from left to right, suggesting a serial item-by-item reading-specific strategy comparable to alphabetic reading. For non-letters, in contrast, a symmetrical U-shaped function best explained the RT variance, suggesting a symmetrical scanning-out from the central to the terminal positions of the string. Since the design precludes orthographic and semantic influences, it can be concluded that a reading-specific strategy for alphabetic processing is automatically activated if the string is scanned for a letter-target. Thus, the pre-designated target triggers the strategy for processing the string and determines related position effects. The results suggest that effects from earlier studies, which showed an analytic processing preference for isolated letters (APPLE) in recognition tasks, as a consequence of literacy acquisition, generalize to the processing of letters in strings. Microorganism-derived dissolved organic nitrogen (mDON) represents a significant and inevitable portion of dissolved organic nitrogen (DON) in the wastewater biotreatment processes. In the existing method, mDON concentrations are indirectly measured by the values of DON concentrations from the reactors with DON-free influent. However, this becomes problematic when influent contains DON. Especially when the real wastewater is involved, the paucity of the direct methods to quantitatively measure mDON is a major barrier to further research. This limitation is due to the difficulty of segregating mDON from the other nitrogenous organics, e.g., influent DON. In this study, we propose the ASM-mDON model based on ASM #1, which incorporates the production and consumption of mDON in the activated sludge processes to predict the mDON concentrations. In four independent lab-scale tests, our model was established and calibrated to obtain the accurate values of mDON (R2 = 0.929, p less then 0.05), and the validity and applicability of the model were successfully examined by comparing the simulated and measured data. Moreover, the universality of the ASM-mDON model was further confirmed by simulating mDON production in a full-scale wastewater treatment plant. A reasonable prediction of mDON formation was shown in a full-scale test (1.98 ± 0.71 mg/L in June and 1.51 ± 0.54 mg/L in July) and is indirectly supported by an algal bioassay (p less then 0.05, t-test). This study provides a useful approach to the efficient and accurate evaluation of mDON formation, which will improve current strategies designed to minimize the effluent mDON in wastewater bioprocesses. Using persulfate (PS) oxidation to remove the persistent perfluorooctanoic acid (PFOA) in water typically requires an elevated temperature or an extended reaction time. Under relatively ambient temperatures (15-45 °C), feasibility of employing PS with iron-modified activated carbon (AC) for PFOA oxidation was evaluated. With presence of Fe/AC in PS oxidation, 61.7% of PFOA was decomposed to fluoride ions and intermediates of short-chain perfluorinated carboxylic acids (PFCAs) with a 41.9% defluorination efficiency at 25 °C after 10 h. Adsorption of PFOA onto Fe/AC can be regarded as a pre-concentration step prior to subsequent oxidation of PFOA. Fe/AC not only removes PFOA through adsorption, but also activates PS to form sulfate radicals that accelerate the decomposition and mineralization of PFOA. With Fe/AC in the PS system, activation energies (Ea) of PFOA removal and defluorination were significantly reduced from 66.8 to 13.2 and 97.3 to 14.5 kJ/mol, respectively. It implies that PFOA degradation and defluorination could proceed at a lower reaction temperature within a shorter reaction time.0 Comentários 0 Compartilhamentos 161 Visualizações 0 Anterior -
BACKGROUND Myeloid derived suppressor cells (MDSCs) present a significant obstacle to cancer immunotherapy because they dampen anti-tumor cytotoxic T cell responses. Previous groups, including our own, have reported on the myelo-depletive effects of certain chemotherapy agents. We have shown previously that decitabine increased tumor cell Class I and tumor antigen expression, increased ability of tumor cells to stimulate T lymphocytes, depleted tumor-induced MDSC in vivo and augmented immunotherapy of a murine mammary carcinoma. RESULTS In this study, we expand upon this observation by testing a next-generation DNA methyltransferase inhibitor (DNMTi), guadecitabine, which has increased stability in the circulation. Using the 4 T1 murine mammary carcinoma model, in BALB/cJ female ****, we found that guadecitabine significantly reduces tumor burden in a T cell-dependent manner by preventing excessive myeloid proliferation and systemic accumulation of MDSC. The remaining MDSC were shifted to an antigen-presenting phenotype. Building upon our previous publication, we show that guadecitabine enhances the therapeutic effect of adoptively transferred antigen-experienced lymphocytes to diminish tumor growth and improve overall survival. We also show guadecitabine's versatility with similar tumor reduction and augmentation of immunotherapy in the C57BL/6 J E0771 murine breast cancer model. CONCLUSIONS Guadecitabine depleted and altered MDSC, inhibited growth of two different murine mammary carcinomas in vivo, and augmented immunotherapeutic efficacy. Based on these findings, we believe the immune-modulatory effects of guadecitabine can help rescue anti-tumor immune response and contribute to the overall effectiveness of current cancer immunotherapies.A recent article in ****Genomics describes a new bioinformatics tool, HumanMycobiomeScan, to classify fungal taxa in metagenomic samples. This tool was used to characterize the gut mycobiome of hunter-gatherers and Western populations, resulting in the identification of a range of fungal species in the vast majority of samples. In the HumanMycobiomeScan pipeline, sequence reads are mapped against a reference database containing fungal genome sequences only. We argue that using reference databases comprised of a single taxonomic group leads to an unacceptably high number of false-positives due to (i) mapping to conserved genetic regions in reference genomes, and (ii) sequence contamination in the assembled reference genomes. To demonstrate this, we replaced the HumanMycobiomeScan's fungal reference database with one containing genome sequences of amphibians and reptiles and re-analysed their case study. The classification pipeline recovered all species present in the reference database, revealing turtles (Geoemydidae), bull frogs (Pyxicephalidae) and snakes (Colubridae) as the most abundant herpetological taxa in the human gut. We also re-analysed their case study using a kingdom-agnostic pipeline. This revealed that while the gut of hunter-gatherers and Western subjects may be colonized by a range of microbial eukaryotes, only three fungal families were retrieved. These results highlight the pitfalls of using taxon-specific reference databases for metagenome classification, even when they are comprised of curated whole genome data. We propose that databases containing all domains of life provide the most suitable option for metagenomic species profiling, especially when targeting microbial eukaryotes.BACKGROUND Transdermal drug delivery has many advantages compared to other routes. However; the barrier function of the stratum corneum limits the use of the skin as an administrative route for medications. Different methods were investigated to alter the barrier function of the stratum corneum. https://www.selleckchem.com/products/gc376-sodium.html Applying different ultrasound waves could enhance the skin's permeability. OBJECTIVE Study the effect of ultrasonic waves on the alteration of skin natural barrier function, to improve the permeability of the skin to Piroxicam using three-dimension skin (EpiDermTM) as a skin model for the investigation. METHOD The effect of ultrasound at 1 MHz and 20 kHz on the permeation of Piroxicam across the three-dimensional skin equivalent using a Franz diffusion cell, was evaluated and the concentration of Piroxicam in the receiving compartment was determined using liquid chromatography method. RESULTS The permeation of Piroxicam enhanced by 199% when therapeutic ultrasound at 1 MHz frequency was used. Significant permeation enhancement was found also upon utilizing low frequency sonophoresis at 20 kHz (427%) with no apparent damage to the membrane. CONCLUSION Sonophoresis has a positive effect on enhancing skin permeability. The enhancement level was largely dependent on the sonication factors; frequency, intensity and the length of treatment. Multiple mechanisms of action might be involved in permeation improvement of the piroxicam molecule. Those mechanisms are largely dependent on the ultrasonic conditions. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.BACKGROUND Meropenem standard doses are based on the minimum inhibitory concentration of sensitive pathogens and the pharmacokinetic parameter of not critically ill patients. We compared the efficacy of high versus standard dose of meropenem in ventilator-associated pneumonia (VAP). METHODS 24 out of 34 eligible patients were randomized to receive meropenem 3 g q8h (high dose group, 11 patients) or 2 g q8h (standard dose group, 13 patients) as a 3h infusion. Primary outcome was considered as clinical success that was defined as stable hemodynamic, improved sequential organ failure assessment (SOFA) score, stable or improved PaO2/FiO2 after 7 days. A sputum culture was taken before intervention. RESULTS Clinical success rate was not significantly different between the high and standard dose group (54.5% vs. 38.5%, P= 0.431). There was a significant difference in reduction of clinical pulmonary infection score (CPIS) compared to high dose with standard group (P=0.038). SOFA score declined significantly in high dose group through the study (P=0.
BACKGROUND Myeloid derived suppressor cells (MDSCs) present a significant obstacle to cancer immunotherapy because they dampen anti-tumor cytotoxic T cell responses. Previous groups, including our own, have reported on the myelo-depletive effects of certain chemotherapy agents. We have shown previously that decitabine increased tumor cell Class I and tumor antigen expression, increased ability of tumor cells to stimulate T lymphocytes, depleted tumor-induced MDSC in vivo and augmented immunotherapy of a murine mammary carcinoma. RESULTS In this study, we expand upon this observation by testing a next-generation DNA methyltransferase inhibitor (DNMTi), guadecitabine, which has increased stability in the circulation. Using the 4 T1 murine mammary carcinoma model, in BALB/cJ female mice, we found that guadecitabine significantly reduces tumor burden in a T cell-dependent manner by preventing excessive myeloid proliferation and systemic accumulation of MDSC. The remaining MDSC were shifted to an antigen-presenting phenotype. Building upon our previous publication, we show that guadecitabine enhances the therapeutic effect of adoptively transferred antigen-experienced lymphocytes to diminish tumor growth and improve overall survival. We also show guadecitabine's versatility with similar tumor reduction and augmentation of immunotherapy in the C57BL/6 J E0771 murine breast cancer model. CONCLUSIONS Guadecitabine depleted and altered MDSC, inhibited growth of two different murine mammary carcinomas in vivo, and augmented immunotherapeutic efficacy. Based on these findings, we believe the immune-modulatory effects of guadecitabine can help rescue anti-tumor immune response and contribute to the overall effectiveness of current cancer immunotherapies.A recent article in BMC Genomics describes a new bioinformatics tool, HumanMycobiomeScan, to classify fungal taxa in metagenomic samples. This tool was used to characterize the gut mycobiome of hunter-gatherers and Western populations, resulting in the identification of a range of fungal species in the vast majority of samples. In the HumanMycobiomeScan pipeline, sequence reads are mapped against a reference database containing fungal genome sequences only. We argue that using reference databases comprised of a single taxonomic group leads to an unacceptably high number of false-positives due to (i) mapping to conserved genetic regions in reference genomes, and (ii) sequence contamination in the assembled reference genomes. To demonstrate this, we replaced the HumanMycobiomeScan's fungal reference database with one containing genome sequences of amphibians and reptiles and re-analysed their case study. The classification pipeline recovered all species present in the reference database, revealing turtles (Geoemydidae), bull frogs (Pyxicephalidae) and snakes (Colubridae) as the most abundant herpetological taxa in the human gut. We also re-analysed their case study using a kingdom-agnostic pipeline. This revealed that while the gut of hunter-gatherers and Western subjects may be colonized by a range of microbial eukaryotes, only three fungal families were retrieved. These results highlight the pitfalls of using taxon-specific reference databases for metagenome classification, even when they are comprised of curated whole genome data. We propose that databases containing all domains of life provide the most suitable option for metagenomic species profiling, especially when targeting microbial eukaryotes.BACKGROUND Transdermal drug delivery has many advantages compared to other routes. However; the barrier function of the stratum corneum limits the use of the skin as an administrative route for medications. Different methods were investigated to alter the barrier function of the stratum corneum. https://www.selleckchem.com/products/gc376-sodium.html Applying different ultrasound waves could enhance the skin's permeability. OBJECTIVE Study the effect of ultrasonic waves on the alteration of skin natural barrier function, to improve the permeability of the skin to Piroxicam using three-dimension skin (EpiDermTM) as a skin model for the investigation. METHOD The effect of ultrasound at 1 MHz and 20 kHz on the permeation of Piroxicam across the three-dimensional skin equivalent using a Franz diffusion cell, was evaluated and the concentration of Piroxicam in the receiving compartment was determined using liquid chromatography method. RESULTS The permeation of Piroxicam enhanced by 199% when therapeutic ultrasound at 1 MHz frequency was used. Significant permeation enhancement was found also upon utilizing low frequency sonophoresis at 20 kHz (427%) with no apparent damage to the membrane. CONCLUSION Sonophoresis has a positive effect on enhancing skin permeability. The enhancement level was largely dependent on the sonication factors; frequency, intensity and the length of treatment. Multiple mechanisms of action might be involved in permeation improvement of the piroxicam molecule. Those mechanisms are largely dependent on the ultrasonic conditions. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.BACKGROUND Meropenem standard doses are based on the minimum inhibitory concentration of sensitive pathogens and the pharmacokinetic parameter of not critically ill patients. We compared the efficacy of high versus standard dose of meropenem in ventilator-associated pneumonia (VAP). METHODS 24 out of 34 eligible patients were randomized to receive meropenem 3 g q8h (high dose group, 11 patients) or 2 g q8h (standard dose group, 13 patients) as a 3h infusion. Primary outcome was considered as clinical success that was defined as stable hemodynamic, improved sequential organ failure assessment (SOFA) score, stable or improved PaO2/FiO2 after 7 days. A sputum culture was taken before intervention. RESULTS Clinical success rate was not significantly different between the high and standard dose group (54.5% vs. 38.5%, P= 0.431). There was a significant difference in reduction of clinical pulmonary infection score (CPIS) compared to high dose with standard group (P=0.038). SOFA score declined significantly in high dose group through the study (P=0.0 Comentários 0 Compartilhamentos 170 Visualizações 0 Anterior -
Tumor necrosis factor α (TNFα) and its receptors contribute to rejection of transplanted cells and organs. To elucidate how TNFα affects xenograft rejection, we previously cloned the cDNA of pig TNF-receptor 2 (pTNFR2) and found four isoforms one comprising the full receptor with four cysteine-rich domains (CRD), a shorter variant (pTNFR2ΔE7-10) encoding for a soluble isoform, another lacking exon 4 (pTNFR2ΔE4) displaying only 3 CRD and poor ligand binding, and the smallest one generated by the two alternative splicings. All isoforms contained the pre-ligand assembly domain (PLAD) responsible for receptor trimerization. We now investigated their roles by structural, expression, and subcellular localization studies. Structural in silico analyses identified four amino acids potentially involved in TNFα binding and lacking in pTNFR2ΔE4. Quantitative RT-PCR determined regulated expression affecting the two pTNFR2 alternative splicings in cytokine-stimulated porcine aortic endothelial cells (PAEC). Particularly, human IL-1α and TNFα produced a strong mRNA upregulation of all isoforms, being the full receptor the predominant one. However, expression of pTNFR2 on PAEC did not correlate with mRNA and decreased after 24-hour exposure to IL-1α or TNFα. Notably, confocal microscopy confirmed the presence of pTNFR2 inside and on the plasma membrane, whereas pTNFR2ΔE4 located only intracellularly. https://www.selleckchem.com/products/gsk1120212-jtp-74057.html Most interestingly, FRET analyses showed that membrane-bound isoforms pTNFR2 and pTNFR2ΔE4 colocalized intracellularly and associated through the PLAD. Our data show that pTNFR2ΔE4 bind and may retain the full receptor intracellularly. This mechanism has not been described in other species and represents a particularity that may affect the pathophysiology of pig xenografts.
Psychosocial costs, or quality of life costs, account for psychological distress, pain, suffering and other negative experiences associated with cancer. They contribute to the overall economic burden of cancer that patients experience. But this category of costs remains poorly understood. This hinders opportunities to make the best cancer control policy decisions. This study explored the psychosocial cost burden associated with cancer, how studies measure psychosocial costs and the impact of this burden.
A systematic literature review of academic and grey literature published from 2008 to 2018 was conducted by searching electronic databases, guided by the Institute of Medicine's conceptualization of psychosocial burden. Results were analyzed using a narrative synthesis and a weighted proportion of populations affected was calculated. Study quality was assessed using the Ottawa-Newcastle instrument.
A total of 25 studies were included. There was variation in how psychosocial costs were conceptualized andnt would help to elevate this issue for researchers and decision makers. At two-thirds of the total economic burden of cancer, economic evaluations should account for psychosocial costs to better inform decision-making. More support is needed to address the psychosocial cost burden faced by patients and their families.The cultivation of compassion is associated with beneficial effects on physical and psychological health, satisfaction with life and social relationships. However, some individuals, especially those high in psychopathological symptoms or those with particular disorders such as borderline personality disorder (BPD) may demonstrate pronounced fears of engagement in compassionate experiences or behaviours. Furthermore, fears of compassion have been found to impede progress in psychotherapy. The 38-item fears of compassion scales (FCS) is a self-report questionnaire for measuring trait levels of fears of compassion (a) one receives from others (FCFO), (b) one feels towards others (FCTO) and (c) one feels for oneself (self-compassion; FSC). The FCS is an internationally used instrument of proven validity and reliability in both clinical and nonclinical samples. In the present study, a German translation of the FCS including its three subscales was provided, and the psychometric properties were examined in 430 participants from four different samples (a) a sample from the general population; (b) a mixed sample of psychiatric residential and outpatients; (c) a clinical sample of residential and outpatients with a primary diagnosis of BPD and (d) a sample of healthy control participants. Internal consistencies were excellent for the German version of the FSC and acceptable to excellent for its subscales. Correlations with established measures of mental health demonstrate its validity. Additionally, the German FCS discriminates significantly between individuals from the general population and patients, thus supporting its specificity. The German FCS is suitable to detect potential obstacles in cultivating compassion in psychotherapeutic treatments and beyond.This paper examines the relationship between community care services and ageing in place in urban China. Using data from the 2010 Sample Survey on Aged Population in Urban/Rural China, and within the framework of a revised version of Andersen's model, the paper applies multilevel models and analyses the effects of community care on the preference between ageing in place and institutional care, and reveals that ageing in place is preferred even in urban China. However, the existence of community care services had no significant effect on the preference for ageing in place. The paper concludes by arguing that China needs to develop its community care services and promote the idea of community care in both culture and policy. Realising ageing in place also requires a multidisciplinary approach. A model of shared care, between family and state, is particularly appropriate for China.
To examine the concordance rate of non-chromosomal congenital malformations in twin pairs based on zygosity.
Retrospective cohort study.
A tertiary hospital in Korea.
Twin pairs born at Seoul National University Hospital between 2001 and 2019.
Congenital malformations were diagnosed by postnatal workups of neonates or autopsy in cases of stillborn infants. Zygosity was confirmed by sex, chorionicity and DNA analysis.
Concordance rate of congenital malformations in twin pairs based on zygosity.
In total, 3386 twin pairs were included. The risk of a congenital malformation in the index twin increased significantly if the co-twin had the congenital malformation, and the concordance rate was higher in monozygotic (MZ) than in dizygotic (DZ) twins (37.04 versus 16.77, P<0.001). An increased risk of a congenital malformation in the presence of the same congenital malformation in the co-twin was observed only for malformations of the nervous system, eye/ear/face/neck, circulatory system, cleft lip/palate, genital organs, urinary system and musculoskeletal system.
Tumor necrosis factor α (TNFα) and its receptors contribute to rejection of transplanted cells and organs. To elucidate how TNFα affects xenograft rejection, we previously cloned the cDNA of pig TNF-receptor 2 (pTNFR2) and found four isoforms one comprising the full receptor with four cysteine-rich domains (CRD), a shorter variant (pTNFR2ΔE7-10) encoding for a soluble isoform, another lacking exon 4 (pTNFR2ΔE4) displaying only 3 CRD and poor ligand binding, and the smallest one generated by the two alternative splicings. All isoforms contained the pre-ligand assembly domain (PLAD) responsible for receptor trimerization. We now investigated their roles by structural, expression, and subcellular localization studies. Structural in silico analyses identified four amino acids potentially involved in TNFα binding and lacking in pTNFR2ΔE4. Quantitative RT-PCR determined regulated expression affecting the two pTNFR2 alternative splicings in cytokine-stimulated porcine aortic endothelial cells (PAEC). Particularly, human IL-1α and TNFα produced a strong mRNA upregulation of all isoforms, being the full receptor the predominant one. However, expression of pTNFR2 on PAEC did not correlate with mRNA and decreased after 24-hour exposure to IL-1α or TNFα. Notably, confocal microscopy confirmed the presence of pTNFR2 inside and on the plasma membrane, whereas pTNFR2ΔE4 located only intracellularly. https://www.selleckchem.com/products/gsk1120212-jtp-74057.html Most interestingly, FRET analyses showed that membrane-bound isoforms pTNFR2 and pTNFR2ΔE4 colocalized intracellularly and associated through the PLAD. Our data show that pTNFR2ΔE4 bind and may retain the full receptor intracellularly. This mechanism has not been described in other species and represents a particularity that may affect the pathophysiology of pig xenografts. Psychosocial costs, or quality of life costs, account for psychological distress, pain, suffering and other negative experiences associated with cancer. They contribute to the overall economic burden of cancer that patients experience. But this category of costs remains poorly understood. This hinders opportunities to make the best cancer control policy decisions. This study explored the psychosocial cost burden associated with cancer, how studies measure psychosocial costs and the impact of this burden. A systematic literature review of academic and grey literature published from 2008 to 2018 was conducted by searching electronic databases, guided by the Institute of Medicine's conceptualization of psychosocial burden. Results were analyzed using a narrative synthesis and a weighted proportion of populations affected was calculated. Study quality was assessed using the Ottawa-Newcastle instrument. A total of 25 studies were included. There was variation in how psychosocial costs were conceptualized andnt would help to elevate this issue for researchers and decision makers. At two-thirds of the total economic burden of cancer, economic evaluations should account for psychosocial costs to better inform decision-making. More support is needed to address the psychosocial cost burden faced by patients and their families.The cultivation of compassion is associated with beneficial effects on physical and psychological health, satisfaction with life and social relationships. However, some individuals, especially those high in psychopathological symptoms or those with particular disorders such as borderline personality disorder (BPD) may demonstrate pronounced fears of engagement in compassionate experiences or behaviours. Furthermore, fears of compassion have been found to impede progress in psychotherapy. The 38-item fears of compassion scales (FCS) is a self-report questionnaire for measuring trait levels of fears of compassion (a) one receives from others (FCFO), (b) one feels towards others (FCTO) and (c) one feels for oneself (self-compassion; FSC). The FCS is an internationally used instrument of proven validity and reliability in both clinical and nonclinical samples. In the present study, a German translation of the FCS including its three subscales was provided, and the psychometric properties were examined in 430 participants from four different samples (a) a sample from the general population; (b) a mixed sample of psychiatric residential and outpatients; (c) a clinical sample of residential and outpatients with a primary diagnosis of BPD and (d) a sample of healthy control participants. Internal consistencies were excellent for the German version of the FSC and acceptable to excellent for its subscales. Correlations with established measures of mental health demonstrate its validity. Additionally, the German FCS discriminates significantly between individuals from the general population and patients, thus supporting its specificity. The German FCS is suitable to detect potential obstacles in cultivating compassion in psychotherapeutic treatments and beyond.This paper examines the relationship between community care services and ageing in place in urban China. Using data from the 2010 Sample Survey on Aged Population in Urban/Rural China, and within the framework of a revised version of Andersen's model, the paper applies multilevel models and analyses the effects of community care on the preference between ageing in place and institutional care, and reveals that ageing in place is preferred even in urban China. However, the existence of community care services had no significant effect on the preference for ageing in place. The paper concludes by arguing that China needs to develop its community care services and promote the idea of community care in both culture and policy. Realising ageing in place also requires a multidisciplinary approach. A model of shared care, between family and state, is particularly appropriate for China. To examine the concordance rate of non-chromosomal congenital malformations in twin pairs based on zygosity. Retrospective cohort study. A tertiary hospital in Korea. Twin pairs born at Seoul National University Hospital between 2001 and 2019. Congenital malformations were diagnosed by postnatal workups of neonates or autopsy in cases of stillborn infants. Zygosity was confirmed by sex, chorionicity and DNA analysis. Concordance rate of congenital malformations in twin pairs based on zygosity. In total, 3386 twin pairs were included. The risk of a congenital malformation in the index twin increased significantly if the co-twin had the congenital malformation, and the concordance rate was higher in monozygotic (MZ) than in dizygotic (DZ) twins (37.04 versus 16.77, P<0.001). An increased risk of a congenital malformation in the presence of the same congenital malformation in the co-twin was observed only for malformations of the nervous system, eye/ear/face/neck, circulatory system, cleft lip/palate, genital organs, urinary system and musculoskeletal system.0 Comentários 0 Compartilhamentos 182 Visualizações 0 Anterior -
0001). An analysis of our data compared with the current literature confirmed that subspinal Le Fort I combined with alar cinch suture reduced alar base widening.Severe Acute Respiratory Distress Syndrome caused by a novel human coronavirus SARS-CoV-2 named COVID-19 and declared as a pandemic. This paper reviews the possibility of repurposing angiotensin type 1 receptor (AT1R) antagonists and vitamin D to treat COVID-19. ACE2 protein found on the cell membranes is the target of SARS-CoV-2 for entering into the host cells. Viral spike protein-binding with ACE2 down-regulates it. As ACE2 is known to protect the lung from injuries, SARS-CoV-2-induced ACE2 deficiency may expose patients to lung damage. AT1R antagonists and vitamin D increase the expression of ACE2 independently. Besides, vitamin D suppresses the compensatory increase in renin levels following the inhibition of the renin-angiotensin system by AT1R antagonists. Therefore, a combination of AT1R antagonists and vitamin D may offer protection against COVID-19 induced lung injury.
Obesity and overweight are the most prevailing problem in most countries. Overweight people are very susceptible to diseases such as diabetes, hypertension, cardiovascular disease, metabolic syndrome, and cancers. Adequate intake of micronutrients along with a quality diet that is varied and balanced plays an important role regarding health and the immune system. Numerous studies have investigated the relationship between the quality of diet and different diseases. Genetics is a risk factor of great importance regarding obesity and overweight. Yet, the role of nutrition in relationship with the underlying mechanisms remains unclear and no specific pathways have been identified for this relation.
A valid food frequency questionnaire was employed to assess dietary intake. We calculated the INQ (Index of Nutritional Quality) of each dietary item using the following formulae INQ=consumed amount of a nutrient per 1,000kcal/recommended dietary allowance or adequate intake of that nutrient per 1,000kcal. In a reerweight cases with FTO rs9939609 polymorphism.
Myocardial infarction with nonobstructive coronary arteries (MINOCA) can be clinically categorized as ST-segment elevation (STE) and non-ST-segment elevation (NSTE), whose clinical prognosis are poorly understood. The aim of this study was to compare the clinical outcome and their predictors of patients with STE and NSTE in MINOCA population.
A total of 265 patients with MINOCA (102 with STE, and 163 with NSTE) were consecutively collected. Clinical profile, prognosis, and predictors of all patients were assessed.
The proportion of patients with NSTE was greater than patients with STE in MINOCA population. Patients with NSTE were older and more likely to be female and had a higher incidence of atrial fibrillation. Both high density lipoprotein (HDL) and N-terminal pro-brain natriuretic peptide (NT-proBNP) were higher in the NSTE group. Patients with STE were more likely to have a history of smoking and a higher diastolic blood pressure. During the 1-year follow up, there were no differences in the outcomes between the STE and NSTE groups, with no significant differences in mortality and a similar rate of major adverse cardiovascular events (****) (20.9% vs 19.3%, P=0.767). The multivariable predictors of **** in the NSTE groups were age, lower level of total cholesterol, hypertension, and smoking history, whereas reduced left ventricular ejection fraction, and diabetes mellitus were the multivariable predictors of major adverse cardiac events in the STE group.
There were differences in the clinical profile between STE and NSTE in the MINOCA population, whereas the outcomes during the 1-year follow up were similar. The STE and NSTE groups had different predictive factors for major adverse cardiac events.
There were differences in the clinical profile between STE and NSTE in the MINOCA population, whereas the outcomes during the 1-year follow up were similar. The STE and NSTE groups had different predictive factors for major adverse cardiac events.Dermatomyositis (DM) is an idiopathic inflammatory disorder that presents with proximal muscle weakness and typical DM skin changes. DM can involve other organs such as the lung, esophagus, and heart. Diaphragmatic muscle paralysis is an unrecognized clinical presentation of acute DM exacerbation. A 58-year-old man with a history of DM presented to the hospital after sustaining a cardiorespiratory arrest. Before arrest, he had been suffering from progressive dyspnea and muscle weakness. Immunosuppressive therapy of tacrolimus for DM was recently discontinued due to renal toxicity. Bedside ultrasound of the diaphragm while intubated revealed evidence of bilateral diaphragmatic paralysis. After extubation, supine and upright pulmonary function tests (PFT) and sniff test results strengthened the diagnosis of diaphragmatic paralysis. The patient was worked up for an acute DM exacerbation as the likely etiology of the severe diaphragmatic muscle weakness (diaphragmatic paralysis) and ventilatory failure. Skin and muscle biopsy confirmed the diagnosis of active DM. The patient was treated with high dose steroids and mycophenolate mofetil, following which he soon recovered.
Extracorporeal membrane oxygenation (ECMO) is increasingly used to support adults with severe respiratory failure refractory to conventional measures. In 2011, NHS England commissioned a national service to provide ECMO to adults with refractory acute respiratory failure. Our aims were to characterise the patients admitted to the service, report their outcomes, and highlight characteristics potentially associated with survival.
An observational cohort study was conducted of all patients treated by the NHS England commissioned ECMO service between December 1, 2011 and December 31, 2017. https://www.selleckchem.com/products/ms-275.html Analysis was conducted according to a prespecified protocol (NCT 03979222). Data are presented as median [inter-quartile range, IQR].
A total of 1205 patients were supported with ECMO during the study period; the majority (n=1150; 95%) had veno-venous ECMO alone. The survival rate at ECMO ICU discharge was 74% (n=887). Survivors had a lower median age (43 yr [32-52]), compared with non-survivors (49 y [39-60]). Increased severity of hypoxaemia at time of decision-to-cannulate was associated with a lower probability of survival survivors had a median Sao
of 90% (84-93%; median Pao
/Fio
, 9.
0001). An analysis of our data compared with the current literature confirmed that subspinal Le Fort I combined with alar cinch suture reduced alar base widening.Severe Acute Respiratory Distress Syndrome caused by a novel human coronavirus SARS-CoV-2 named COVID-19 and declared as a pandemic. This paper reviews the possibility of repurposing angiotensin type 1 receptor (AT1R) antagonists and vitamin D to treat COVID-19. ACE2 protein found on the cell membranes is the target of SARS-CoV-2 for entering into the host cells. Viral spike protein-binding with ACE2 down-regulates it. As ACE2 is known to protect the lung from injuries, SARS-CoV-2-induced ACE2 deficiency may expose patients to lung damage. AT1R antagonists and vitamin D increase the expression of ACE2 independently. Besides, vitamin D suppresses the compensatory increase in renin levels following the inhibition of the renin-angiotensin system by AT1R antagonists. Therefore, a combination of AT1R antagonists and vitamin D may offer protection against COVID-19 induced lung injury. Obesity and overweight are the most prevailing problem in most countries. Overweight people are very susceptible to diseases such as diabetes, hypertension, cardiovascular disease, metabolic syndrome, and cancers. Adequate intake of micronutrients along with a quality diet that is varied and balanced plays an important role regarding health and the immune system. Numerous studies have investigated the relationship between the quality of diet and different diseases. Genetics is a risk factor of great importance regarding obesity and overweight. Yet, the role of nutrition in relationship with the underlying mechanisms remains unclear and no specific pathways have been identified for this relation. A valid food frequency questionnaire was employed to assess dietary intake. We calculated the INQ (Index of Nutritional Quality) of each dietary item using the following formulae INQ=consumed amount of a nutrient per 1,000kcal/recommended dietary allowance or adequate intake of that nutrient per 1,000kcal. In a reerweight cases with FTO rs9939609 polymorphism. Myocardial infarction with nonobstructive coronary arteries (MINOCA) can be clinically categorized as ST-segment elevation (STE) and non-ST-segment elevation (NSTE), whose clinical prognosis are poorly understood. The aim of this study was to compare the clinical outcome and their predictors of patients with STE and NSTE in MINOCA population. A total of 265 patients with MINOCA (102 with STE, and 163 with NSTE) were consecutively collected. Clinical profile, prognosis, and predictors of all patients were assessed. The proportion of patients with NSTE was greater than patients with STE in MINOCA population. Patients with NSTE were older and more likely to be female and had a higher incidence of atrial fibrillation. Both high density lipoprotein (HDL) and N-terminal pro-brain natriuretic peptide (NT-proBNP) were higher in the NSTE group. Patients with STE were more likely to have a history of smoking and a higher diastolic blood pressure. During the 1-year follow up, there were no differences in the outcomes between the STE and NSTE groups, with no significant differences in mortality and a similar rate of major adverse cardiovascular events (MACE) (20.9% vs 19.3%, P=0.767). The multivariable predictors of MACE in the NSTE groups were age, lower level of total cholesterol, hypertension, and smoking history, whereas reduced left ventricular ejection fraction, and diabetes mellitus were the multivariable predictors of major adverse cardiac events in the STE group. There were differences in the clinical profile between STE and NSTE in the MINOCA population, whereas the outcomes during the 1-year follow up were similar. The STE and NSTE groups had different predictive factors for major adverse cardiac events. There were differences in the clinical profile between STE and NSTE in the MINOCA population, whereas the outcomes during the 1-year follow up were similar. The STE and NSTE groups had different predictive factors for major adverse cardiac events.Dermatomyositis (DM) is an idiopathic inflammatory disorder that presents with proximal muscle weakness and typical DM skin changes. DM can involve other organs such as the lung, esophagus, and heart. Diaphragmatic muscle paralysis is an unrecognized clinical presentation of acute DM exacerbation. A 58-year-old man with a history of DM presented to the hospital after sustaining a cardiorespiratory arrest. Before arrest, he had been suffering from progressive dyspnea and muscle weakness. Immunosuppressive therapy of tacrolimus for DM was recently discontinued due to renal toxicity. Bedside ultrasound of the diaphragm while intubated revealed evidence of bilateral diaphragmatic paralysis. After extubation, supine and upright pulmonary function tests (PFT) and sniff test results strengthened the diagnosis of diaphragmatic paralysis. The patient was worked up for an acute DM exacerbation as the likely etiology of the severe diaphragmatic muscle weakness (diaphragmatic paralysis) and ventilatory failure. Skin and muscle biopsy confirmed the diagnosis of active DM. The patient was treated with high dose steroids and mycophenolate mofetil, following which he soon recovered. Extracorporeal membrane oxygenation (ECMO) is increasingly used to support adults with severe respiratory failure refractory to conventional measures. In 2011, NHS England commissioned a national service to provide ECMO to adults with refractory acute respiratory failure. Our aims were to characterise the patients admitted to the service, report their outcomes, and highlight characteristics potentially associated with survival. An observational cohort study was conducted of all patients treated by the NHS England commissioned ECMO service between December 1, 2011 and December 31, 2017. https://www.selleckchem.com/products/ms-275.html Analysis was conducted according to a prespecified protocol (NCT 03979222). Data are presented as median [inter-quartile range, IQR]. A total of 1205 patients were supported with ECMO during the study period; the majority (n=1150; 95%) had veno-venous ECMO alone. The survival rate at ECMO ICU discharge was 74% (n=887). Survivors had a lower median age (43 yr [32-52]), compared with non-survivors (49 y [39-60]). Increased severity of hypoxaemia at time of decision-to-cannulate was associated with a lower probability of survival survivors had a median Sao of 90% (84-93%; median Pao /Fio , 9.0 Comentários 0 Compartilhamentos 184 Visualizações 0 Anterior -
5%) the analyses unraveled pathogenetic variants in ABCC6 and COL4A1 genes, leading to a definite genetic diagnosis with a great beneficial impact on patients management, while results were null in the remaining patients. These findings suggest a high complexity and variability of the included stroke phenotypes, that could not be fully accounted for by the genes tested in the present study. A wider gene panel or an unbiased genomic approach may be better suited and advisable to explain a greater proportion of pediatric and perinatal stroke events.Mutations in the gene kyphoscoliosis peptidase (KY) are known to cause myofibrillar myopathy-7 and hereditary spastic paraplegia. https://www.selleckchem.com/products/eprosartan-mesylate.html We investigated the genetic cause of a complex neurological phenotype in a consanguineous Pakistani family with four affected members, manifesting lower limb spasticity and weakness, toe walking, pes equinovarus, and a speech disorder. Genome-wide linkage analysis with microsatellite markers delineated chromosome 3q22.2-q24 harboring the disease gene. Whole exome sequencing was performed for two subjects, identifying a homozygous 14-bp frameshift deletion NM_178554.6c.842_855del; p(Val281GlyfsTer18) in KY. The variant segregated with the phenotype and was absent from public databases and 100 ethnically matched controls. We confirm a novel homozygous KY variant causing a complex neurological phenotype in this family. A review of previously reported KY variants suggests that variants in this gene can cause a spectrum of neurological phenotypes.Bicyclol, a novel hepatoprotective agent, has been widely used to treat chronic viral hepatitis and drug-induced liver injury (DILI). However, its metabolic characteristics remains to be explored, especially in humans. The current study aimed to identify major metabolites and specific metabolizing enzymes involved in bicyclol metabolism in vitro and in vivo using high performance liquid chromatography coupled with Q-Exactive orbitrap mass spectrometry (HPLC-Q-Exactive Orbitrap/MS). After incubation with liver microsomes and oral administration to rats, dogs and humans, a total of nine metabolites of bicyclol were identified including M1 (methyl ester hydrolysate product), M2-M3 (demethylated bicyclol), M4-M5 (demethoxy or dehydroxymethyl bicyclol), M6 (glucuronidated bicyclol) and M7-M9 (glucuronide conjugates of metabolites). Among these metabolites, M2 and M3 were the major phase I metabolites mainly mediated by CYP2C19 and CYP3A4, while M6 was the dominant phase II metabolite primarily catalyzed by UGT2B4. In this study, species-related metabolic difference among rats, dogs and humans were observed. In humans and dogs, M6 (glucuronidated bicyclol) was the most abundant circulating metabolite (higher than the parent drug) in the blood after oral administration, while the parent drug was the highest in rats. M4 and M5 were rats-specific metabolites whereas M1 and M9 were absent in dogs in vivo. The metabolism of bicyclol was demonstrated as demethylation and glucuronidation mediated by multiple drug metabolizing enzymes in different species. Our findings systematically elucidated the metabolic sites and routes of bicyclol in human for the first time, which may be helpful for rational combined application in clinic and further study of metabolites-related efficacy or toxicity.Fluid sampling from the gastrointestinal (GI) tract has been applied as a valuable tool to gain more insight into the fluids present in the human GI tract and to explore the dynamic interplay of drug release, dissolution, precipitation and absorption after drug product administration to healthy subjects. In the last twenty years, collaborative initiatives have led to a plethora of clinical aspiration studies that aimed to unravel the luminal drug behavior of an orally administered drug product. The obtained drug concentration-time profiles from different segments in the GI tract were a valuable source of information to optimize and/or validate predictive in vitro and in silico tools, frequently applied in the non-clinical stage of drug product development. Sampling techniques are presently not only being considered as a stand-alone technique but are also used in combination with other in vivo techniques (e.g., gastric motility recording, magnetic resonance imaging (MRI)). By doing so, various physiological variables can be mapped simultaneously and evaluated for their impact on luminal drug and formulation behavior. This comprehensive review aims to describe the history, challenges and opportunities of the aspiration technique with a specific focus on how this technique can unravel the luminal behavior of drug products inside the human GI tract by providing a summary of studies performed over the last 20 years. A section 'Best practices' on how to perform the studies and how to treat the aspirated samples is described. In the conclusion, we focus on future perspectives concerning this technique.Dysregulation of intestinal microbiota accelerates the development of type 2 diabetes. Probiotics are potential adjunctive therapy in the treatment of diabetes. This study investigated the anti-diabetic mechanism of 14 composite probiotics. Results showed that treatment with 14 composite probiotics improved intestinal microbiota equilibrium by increasing the population of short-chain fatty acids (SCFAs)-producing bacteria and decreasing the number of harmful bacteria. Further, the probiotics significantly improved blood glucose metabolism by promoting glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) secretion. These effects were ascribed to the activation of GPR43/41, restoration of the pancreatic structure, the elevation of insulin secretion and balancing of blood glucose-related parameters. Additionally, the 14 composite probiotics markedly restored gut barrier function via activating antioxidant enzymes, promoting tight junction protein expression, inhibiting the activity of pro-inflammatory factors and improving the morphology of the colon. Furthermore, the 14 composite probiotics upregulated M2 polarization factors and downregulated M1 polarization factors, possibly through TLRs/MyD88/NF-κB signaling pathway. These results indicate that the 14 composite probiotics can potentially improve diabetes prognosis.
5%) the analyses unraveled pathogenetic variants in ABCC6 and COL4A1 genes, leading to a definite genetic diagnosis with a great beneficial impact on patients management, while results were null in the remaining patients. These findings suggest a high complexity and variability of the included stroke phenotypes, that could not be fully accounted for by the genes tested in the present study. A wider gene panel or an unbiased genomic approach may be better suited and advisable to explain a greater proportion of pediatric and perinatal stroke events.Mutations in the gene kyphoscoliosis peptidase (KY) are known to cause myofibrillar myopathy-7 and hereditary spastic paraplegia. https://www.selleckchem.com/products/eprosartan-mesylate.html We investigated the genetic cause of a complex neurological phenotype in a consanguineous Pakistani family with four affected members, manifesting lower limb spasticity and weakness, toe walking, pes equinovarus, and a speech disorder. Genome-wide linkage analysis with microsatellite markers delineated chromosome 3q22.2-q24 harboring the disease gene. Whole exome sequencing was performed for two subjects, identifying a homozygous 14-bp frameshift deletion NM_178554.6c.842_855del; p(Val281GlyfsTer18) in KY. The variant segregated with the phenotype and was absent from public databases and 100 ethnically matched controls. We confirm a novel homozygous KY variant causing a complex neurological phenotype in this family. A review of previously reported KY variants suggests that variants in this gene can cause a spectrum of neurological phenotypes.Bicyclol, a novel hepatoprotective agent, has been widely used to treat chronic viral hepatitis and drug-induced liver injury (DILI). However, its metabolic characteristics remains to be explored, especially in humans. The current study aimed to identify major metabolites and specific metabolizing enzymes involved in bicyclol metabolism in vitro and in vivo using high performance liquid chromatography coupled with Q-Exactive orbitrap mass spectrometry (HPLC-Q-Exactive Orbitrap/MS). After incubation with liver microsomes and oral administration to rats, dogs and humans, a total of nine metabolites of bicyclol were identified including M1 (methyl ester hydrolysate product), M2-M3 (demethylated bicyclol), M4-M5 (demethoxy or dehydroxymethyl bicyclol), M6 (glucuronidated bicyclol) and M7-M9 (glucuronide conjugates of metabolites). Among these metabolites, M2 and M3 were the major phase I metabolites mainly mediated by CYP2C19 and CYP3A4, while M6 was the dominant phase II metabolite primarily catalyzed by UGT2B4. In this study, species-related metabolic difference among rats, dogs and humans were observed. In humans and dogs, M6 (glucuronidated bicyclol) was the most abundant circulating metabolite (higher than the parent drug) in the blood after oral administration, while the parent drug was the highest in rats. M4 and M5 were rats-specific metabolites whereas M1 and M9 were absent in dogs in vivo. The metabolism of bicyclol was demonstrated as demethylation and glucuronidation mediated by multiple drug metabolizing enzymes in different species. Our findings systematically elucidated the metabolic sites and routes of bicyclol in human for the first time, which may be helpful for rational combined application in clinic and further study of metabolites-related efficacy or toxicity.Fluid sampling from the gastrointestinal (GI) tract has been applied as a valuable tool to gain more insight into the fluids present in the human GI tract and to explore the dynamic interplay of drug release, dissolution, precipitation and absorption after drug product administration to healthy subjects. In the last twenty years, collaborative initiatives have led to a plethora of clinical aspiration studies that aimed to unravel the luminal drug behavior of an orally administered drug product. The obtained drug concentration-time profiles from different segments in the GI tract were a valuable source of information to optimize and/or validate predictive in vitro and in silico tools, frequently applied in the non-clinical stage of drug product development. Sampling techniques are presently not only being considered as a stand-alone technique but are also used in combination with other in vivo techniques (e.g., gastric motility recording, magnetic resonance imaging (MRI)). By doing so, various physiological variables can be mapped simultaneously and evaluated for their impact on luminal drug and formulation behavior. This comprehensive review aims to describe the history, challenges and opportunities of the aspiration technique with a specific focus on how this technique can unravel the luminal behavior of drug products inside the human GI tract by providing a summary of studies performed over the last 20 years. A section 'Best practices' on how to perform the studies and how to treat the aspirated samples is described. In the conclusion, we focus on future perspectives concerning this technique.Dysregulation of intestinal microbiota accelerates the development of type 2 diabetes. Probiotics are potential adjunctive therapy in the treatment of diabetes. This study investigated the anti-diabetic mechanism of 14 composite probiotics. Results showed that treatment with 14 composite probiotics improved intestinal microbiota equilibrium by increasing the population of short-chain fatty acids (SCFAs)-producing bacteria and decreasing the number of harmful bacteria. Further, the probiotics significantly improved blood glucose metabolism by promoting glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) secretion. These effects were ascribed to the activation of GPR43/41, restoration of the pancreatic structure, the elevation of insulin secretion and balancing of blood glucose-related parameters. Additionally, the 14 composite probiotics markedly restored gut barrier function via activating antioxidant enzymes, promoting tight junction protein expression, inhibiting the activity of pro-inflammatory factors and improving the morphology of the colon. Furthermore, the 14 composite probiotics upregulated M2 polarization factors and downregulated M1 polarization factors, possibly through TLRs/MyD88/NF-κB signaling pathway. These results indicate that the 14 composite probiotics can potentially improve diabetes prognosis.0 Comentários 0 Compartilhamentos 199 Visualizações 0 Anterior -
Herein, cobalt-involved redox in a magnetically responsive drug-loaded nanocatalyst (PTX/Co-Lips@Fe3O4) was used to convert Fe(iii) to Fe(ii) for enhancing tumor ferrotherapy for the first time. Moreover, this work highlighted an "all in one" strategy (1) targeting, chemotherapy, and ferrotherapy in one nanomedicine, and (2) a decrease in GSH quantity, increase in the quantity of efficient catalytic ions, and use of a magnetic field, all in one tumor ferrotherapy enhancement approach.In this work, we report the fabrication of continuous transparent and flexible supercapacitors by depositing a CNT network onto a polymer electrolyte membrane directly from an aerogel of ultra-long CNTs produced floating in the gas phase. The supercapacitors show a combination of a power density of 1370 kW kg-1 at high transmittance (ca. 70%), and high electrochemical stability during extended cycling (>94% capacitance retention over 20 000 cycles) and against repeated 180° flexural deformation. They represent a significant enhancement of 1-3 orders of magnitude compared to prior state-of-the-art transparent supercapacitors based on graphene, CNTs, and rGO. These features mainly arise from the exceptionally long length of CNTs, which makes the material behave as a bulk conductor instead of an aspect ratio-limited percolating network, even for electrodes with >90% transparency. The electrical and capacitive figures-of-merit for the transparent conductor are FoMe = 2.7, and FoMc = 0.46 F S-1 cm-2 respectively.Cancer-derived extracellular vesicles (EVs) have attracted considerable attention for clinical diagnosis. However, a limiting factor in current EV assays is the ability to detect various EV cancer biomarkers expressed at different locations. Here, we report a biomimetic multifunctional nanoplatform for multilayer imaging of cancer biomarkers from the EV surface to the interior without complex pretreatment. Constructed from polydopamine-wrapped gold nanoparticles modified with multiple functional molecules, this nanoplatform can capture EVs from complex samples and target different EV cancer biomarkers for imaging analysis at the single-vesicle level. Combined with 96-well plates, this assay can distinguish cancer cell-derived EVs from normal ones in a high-throughput manner. Using serum samples, EVs from hepatocellular carcinoma (HCC) patients can be distinguished from healthy controls. This convenient workflow represents a promising tool for EV-based cancer diagnosis.Lanthanide-doped upconversion nanoparticles (UCNPs) are promising bioimaging agents that emit light under near infra-red excitation, capable of penetrating deep in biotissues with a high signal-to-noise ratio. Their successful implementation is principally associated with surface functionalization. Here, we report on UCNP surface modification with highly hydrophilic, endogenous, non-toxic, non-immunogenic colominic acid, conferring "stealth" properties. We proposed surface functionalization of UCNPs based on a two-step strategy, which consists of hydrophilization with polyethyleneimine and attachment of colominic acid by electrostatic or covalent bond formation. Analysis revealed that regardless of the nature of the bond, colominic acid acted as a non-cytotoxic UCNP surface coating with low nonspecific blood protein adsorption. UCNP-colominic acid nanocomplexes exhibited low uptake by macrophages in vitro, which plays an active role in inflammatory reactions. We demonstrated the superiority of colominic acid compared to polyethylene glycol coating in terms of the prolonged circulation time in the bloodstream of small animals when injected intravenously. The colominic acid coating made it possible to prolong the UCNP circulation time up to 3 h. This led to the efficient UCNP accumulation in the inflammation site due to microvascular remodeling, accompanied by an enhanced uptake and retention effect. UCNP-assisted imaging of inflammation in the whole-body mode as well as local visualization of blood vessels were acquired in vivo. https://www.selleckchem.com/products/cc-92480.html These collective findings validate the functional significance of UCNP decoration with colominic acid for their application in bioimaging.Ag+ plays an important role in DNA mismatch technology due to its affinity for cytosine in DNA. This article introduces a strategy to control the enzyme digesting reaction by utilizing the characteristics of C-Ag+-C mismatches, effectively regulating and controlling the activity of the E6 DNAzyme via changing the structure of its conservative domain. We designed a series of basic logic gates, a "Yes" Gate, an "Or" Gate and an "Inhibit" Gate. Cysteine (Cys) can combine with Ag+, reducing the concentration of Ag+ in solution, thus restraining the C-Ag+-C mismatch effect. Based on this principle, we regard Cys as a threshold, and designed a type of "Inhibit" Gate based on input quantity by changing the concentration of Ag+, thus generating different statues of logic output. On this basis, the E6 DNAzyme and Ag10c DNAzyme can be integrated into new systems with the function of logic operation circuit based on the control of Ag+ concentration in solution. This system could represent three different states of logical expression by controlling the quantity of Ag+ and Cys.In this work, copper(ii)-containing metal-organic xerogels (Cu-MOXs), which were composed of copper as the central ion and 2,2'-bipyridine-6,6'-dicarboxylic acid as the ligand, were quickly synthesized by a mild facile strategy. The Cu-MOXs exhibited superior catalytic performance for the luminol-H2O2 chemiluminescence (CL) system. The possible mechanism was studied via CL spectra, UV-Vis absorption and electron paramagnetic resonance (ESR). Since dopamine (DA) can inhibit the reaction of this system, a sensitive paper-based CL device for the detection of DA was established. Under the optimal experimental conditions, the linear range of this method was 40-200 nM with a detection limit of 10 nM. The proposed method was used for the determination of DA in urine samples.Hepatocellular carcinoma (HCC) is a severe malignant disease threatening human life. Current chemotherapy methods usually result in poor prognosis with low treatment efficacy and high side effects because of weak targeting specificity and fast acquisition of multidrug resistance (MDR). HCSP4 is a 12-aa peptide previously identified to specifically and sensitively bind to HCC cells and tissues. In this study, a novel class of HCC-targeting doxorubicin (DOX) delivery system, named HCSP4-Lipo-DOX-miR101, was synthesized and investigated for anticancer activity. HCSP4-Lipo-DOX-miR101 exhibited specific HCC targeting characteristics and satisfactory anticancer potency against HepG2 and HepG2/ADR cells, particularly HepG2/ADR cells. Moreover, the expression levels of genes closely related to membrane transport and cancer growth were significantly suppressed. This finding suggests that HCSP4-Lipo-DOX-miR101 can cause DOX-resistant HCC cell death and growth inhibition based on the targeting of MDR-related genes by miR-101.
Herein, cobalt-involved redox in a magnetically responsive drug-loaded nanocatalyst (PTX/Co-Lips@Fe3O4) was used to convert Fe(iii) to Fe(ii) for enhancing tumor ferrotherapy for the first time. Moreover, this work highlighted an "all in one" strategy (1) targeting, chemotherapy, and ferrotherapy in one nanomedicine, and (2) a decrease in GSH quantity, increase in the quantity of efficient catalytic ions, and use of a magnetic field, all in one tumor ferrotherapy enhancement approach.In this work, we report the fabrication of continuous transparent and flexible supercapacitors by depositing a CNT network onto a polymer electrolyte membrane directly from an aerogel of ultra-long CNTs produced floating in the gas phase. The supercapacitors show a combination of a power density of 1370 kW kg-1 at high transmittance (ca. 70%), and high electrochemical stability during extended cycling (>94% capacitance retention over 20 000 cycles) and against repeated 180° flexural deformation. They represent a significant enhancement of 1-3 orders of magnitude compared to prior state-of-the-art transparent supercapacitors based on graphene, CNTs, and rGO. These features mainly arise from the exceptionally long length of CNTs, which makes the material behave as a bulk conductor instead of an aspect ratio-limited percolating network, even for electrodes with >90% transparency. The electrical and capacitive figures-of-merit for the transparent conductor are FoMe = 2.7, and FoMc = 0.46 F S-1 cm-2 respectively.Cancer-derived extracellular vesicles (EVs) have attracted considerable attention for clinical diagnosis. However, a limiting factor in current EV assays is the ability to detect various EV cancer biomarkers expressed at different locations. Here, we report a biomimetic multifunctional nanoplatform for multilayer imaging of cancer biomarkers from the EV surface to the interior without complex pretreatment. Constructed from polydopamine-wrapped gold nanoparticles modified with multiple functional molecules, this nanoplatform can capture EVs from complex samples and target different EV cancer biomarkers for imaging analysis at the single-vesicle level. Combined with 96-well plates, this assay can distinguish cancer cell-derived EVs from normal ones in a high-throughput manner. Using serum samples, EVs from hepatocellular carcinoma (HCC) patients can be distinguished from healthy controls. This convenient workflow represents a promising tool for EV-based cancer diagnosis.Lanthanide-doped upconversion nanoparticles (UCNPs) are promising bioimaging agents that emit light under near infra-red excitation, capable of penetrating deep in biotissues with a high signal-to-noise ratio. Their successful implementation is principally associated with surface functionalization. Here, we report on UCNP surface modification with highly hydrophilic, endogenous, non-toxic, non-immunogenic colominic acid, conferring "stealth" properties. We proposed surface functionalization of UCNPs based on a two-step strategy, which consists of hydrophilization with polyethyleneimine and attachment of colominic acid by electrostatic or covalent bond formation. Analysis revealed that regardless of the nature of the bond, colominic acid acted as a non-cytotoxic UCNP surface coating with low nonspecific blood protein adsorption. UCNP-colominic acid nanocomplexes exhibited low uptake by macrophages in vitro, which plays an active role in inflammatory reactions. We demonstrated the superiority of colominic acid compared to polyethylene glycol coating in terms of the prolonged circulation time in the bloodstream of small animals when injected intravenously. The colominic acid coating made it possible to prolong the UCNP circulation time up to 3 h. This led to the efficient UCNP accumulation in the inflammation site due to microvascular remodeling, accompanied by an enhanced uptake and retention effect. UCNP-assisted imaging of inflammation in the whole-body mode as well as local visualization of blood vessels were acquired in vivo. https://www.selleckchem.com/products/cc-92480.html These collective findings validate the functional significance of UCNP decoration with colominic acid for their application in bioimaging.Ag+ plays an important role in DNA mismatch technology due to its affinity for cytosine in DNA. This article introduces a strategy to control the enzyme digesting reaction by utilizing the characteristics of C-Ag+-C mismatches, effectively regulating and controlling the activity of the E6 DNAzyme via changing the structure of its conservative domain. We designed a series of basic logic gates, a "Yes" Gate, an "Or" Gate and an "Inhibit" Gate. Cysteine (Cys) can combine with Ag+, reducing the concentration of Ag+ in solution, thus restraining the C-Ag+-C mismatch effect. Based on this principle, we regard Cys as a threshold, and designed a type of "Inhibit" Gate based on input quantity by changing the concentration of Ag+, thus generating different statues of logic output. On this basis, the E6 DNAzyme and Ag10c DNAzyme can be integrated into new systems with the function of logic operation circuit based on the control of Ag+ concentration in solution. This system could represent three different states of logical expression by controlling the quantity of Ag+ and Cys.In this work, copper(ii)-containing metal-organic xerogels (Cu-MOXs), which were composed of copper as the central ion and 2,2'-bipyridine-6,6'-dicarboxylic acid as the ligand, were quickly synthesized by a mild facile strategy. The Cu-MOXs exhibited superior catalytic performance for the luminol-H2O2 chemiluminescence (CL) system. The possible mechanism was studied via CL spectra, UV-Vis absorption and electron paramagnetic resonance (ESR). Since dopamine (DA) can inhibit the reaction of this system, a sensitive paper-based CL device for the detection of DA was established. Under the optimal experimental conditions, the linear range of this method was 40-200 nM with a detection limit of 10 nM. The proposed method was used for the determination of DA in urine samples.Hepatocellular carcinoma (HCC) is a severe malignant disease threatening human life. Current chemotherapy methods usually result in poor prognosis with low treatment efficacy and high side effects because of weak targeting specificity and fast acquisition of multidrug resistance (MDR). HCSP4 is a 12-aa peptide previously identified to specifically and sensitively bind to HCC cells and tissues. In this study, a novel class of HCC-targeting doxorubicin (DOX) delivery system, named HCSP4-Lipo-DOX-miR101, was synthesized and investigated for anticancer activity. HCSP4-Lipo-DOX-miR101 exhibited specific HCC targeting characteristics and satisfactory anticancer potency against HepG2 and HepG2/ADR cells, particularly HepG2/ADR cells. Moreover, the expression levels of genes closely related to membrane transport and cancer growth were significantly suppressed. This finding suggests that HCSP4-Lipo-DOX-miR101 can cause DOX-resistant HCC cell death and growth inhibition based on the targeting of MDR-related genes by miR-101.0 Comentários 0 Compartilhamentos 153 Visualizações 0 Anterior -
Human papillomavirus (HPV) infection plays an important role in the etiopathogenesis of oropharyngeal squamous cell carcinomas. HPV detection in these tumours is a positive prognostic marker. The p16 protein expression, which is detected immunohistochemically, is an indirect marker of active HPV infection. Unlike in oropharyngeal carcinoma, in oral carcinoma, the prognostic significance of HPV/p16 positivity is unclear. Some studies even show a worse prognosis in patients withHPV/p16 positive oral carcinoma. The aim of our study is to consider the significance of p16 protein expression in relation to clinicopathological parameters and prognosis in patients with oral squamous cell carcinomas. Methods One hundred and twenty patients treated surgically for oral carcinoma were enrolled in the study. The most common anatomical sites of oral carcinoma were the tongue body (54; 45% of cases) and floor of mouth (35; 29.2% of cases). https://www.selleckchem.com/products/conteltinib-ct-707.html All tumours were analysed immunohistochemically for p16 protein expression. The resharyngeal area remains unclear.
Intra-abdominal candidiasis (IAC) is an invasive fungal infection representing the most common type of invasive Candida infection in surgical intensive care units (ICUs). Recently, decreased antifungal susceptibility and progressive shift in the aetiology of invasive candidiasis has been observed worldwide. We explored IAC epidemiology in surgical ICU.
We retrospectively reviewed the records of 64 patients with IAC admitted at our surgical ICU over a 4-year period (2013-2016). IAC incidence, microbiological results, antifungal therapy, and mortality were analysed.
The cumulative IAC incidence was 18.4 cases per 1000 admissions (2013 12.6; 2014 17.7; 2015 16.8; 2016 24.5), including hospital-acquired IAC incidence (2013 9.8; 2014 13.3; 2015 10.1; 2016 13.3) and community-acquired IAC incidence (2013 2.8; 2014 4.4; 2015 6.7; 2016 11.2). Candida albicans represented the most common species (n = 35, 50.0%) followed by Candida glabrata (n = 15, 21.4%), Candida tropicalis (n = 6, 8.6%) and other yeasts (each ogy of IAC towards an increased proportion of non-albicans Candida species, particularly C. glabrata. Acquired decreased fluconazole susceptibility was related to C. glabrata isolates exclusively. Emergence of decreased antifungal susceptibility has been preceded by increase of non-albicans Candida isolates.
We have revealed slowly raising of overall IAC incidence, more increasing trend in incidence of community-acquired IAC compared to rather steady incidence of hospital-acquired IAC. During period 2013-2016 we have observed a significant shift in the aetiology of IAC towards an increased proportion of non-albicans Candida species, particularly C. glabrata. Acquired decreased fluconazole susceptibility was related to C. glabrata isolates exclusively. Emergence of decreased antifungal susceptibility has been preceded by increase of non-albicans Candida isolates.Phorbol myristate acetate (PMA)-differentiated THP-1 cells are routinely used in lieu of primary macrophages to study macrophage polarization during host-pathogen interactions and disease progression. The phenotypes of THP-1 macrophages are influenced by the level and duration of PMA stimulation and possibly also by the presence of adhesion factors. Here, we use self-organizing maps (SOMs) of single-cell Raman spectra to probe the effects of PMA stimulation conditions and adhesion factors on THP-1 cell differentiation. Raman spectra encoding for biochemical composition were acquired from individual cells on substrates coated with fibronectin or poly-l-lysine before and after stimulation with 20 or 200 nM PMA for two different time intervals. SOMs constructed from these spectra showed the extent of spectral dissimilarity between different chronological cell populations. For all conditions, the SOMs indicated that the spectra acquired from cells after three-day treatment had diverged from those of untreated cells. The SOMs also showed that the higher PMA concentration produced both fully and partially differentiated cells for both adhesion factors after three days, whereas the outcome of stimulation for three days with the lower PMA concentration depended on the adhesion factor. On poly-l-lysine, treatment with 20 nM PMA for three days induced an intermediate stage of differentiation, but the same treatment produced partially and fully differentiated cells when applied to THP-1 cells on fibronectin. These results are consistent with the modulation of the transition of THP-1 monocytes into macrophage-like cells by integrin-binding interactions. Furthermore, differences in culture and stimulation conditions may confound comparison of results from separate studies.ConspectusCancer immunotherapy, which suppresses tumor relapse and metastasis by boosting host immunity and inducing long-term immune memory effects, is emerging as a vital approach to improve the prognosis of patients. Although remarkable efficacy has been observed in some patients, challenges including low response rate, drug resistance, and immune-related adverse effects still limit the clinical application of cancer immunotherapy in broad types of tumors. Immunotherapeutic agents are used to enhance tumor immunogenicity and reverse the effects of the immunosuppressive tumor microenvironment (ITM), but the benefits of monotherapy are mild and transient due to off-target distribution of drugs. To overcome these issues, smart nanosized drug delivery systems (sNDDS) have been developed to enhance tissue specificity, co-deliver multiple drugs, prime immune cells, and amplify immune responses in tumors. Moreover, accumulating knowledge in cancer biology, immunology, and material science has also greatly promote amplified immunotherapeutic efficacy.Mutagenesis through fast neutron (FN) radiation of soybean resulted in a mutant with a 15% increase in seed protein content. A comparative genomic hybridization analysis confirmed that the mutant is lacking 24 genes located at chromosomes 5 and 10. A tandem mass tag-based proteomic profiling of the wild type and the FN mutant revealed 3,502 proteins, of which 206 proteins exhibited increased abundance and 214 proteins showed decreased abundance. Among the abundant proteins, basic 7S globulin increased fourfold, followed by vacuolar-sorting receptor and protein transporters. The differentially expressed proteins were mapped on the global metabolic pathways. It was observed that there was an enrichment of 29 ribosomal proteins, 16 endoplasmic reticular proteins, and several proteins in export metabolic pathways. The deletion of the sequence-specific DNA binding transcription factor along with 23 other genes may have altered the negative regulation of protein syntheses processes, resulting in an increase in the overall protein content of the mutant seed.
Human papillomavirus (HPV) infection plays an important role in the etiopathogenesis of oropharyngeal squamous cell carcinomas. HPV detection in these tumours is a positive prognostic marker. The p16 protein expression, which is detected immunohistochemically, is an indirect marker of active HPV infection. Unlike in oropharyngeal carcinoma, in oral carcinoma, the prognostic significance of HPV/p16 positivity is unclear. Some studies even show a worse prognosis in patients withHPV/p16 positive oral carcinoma. The aim of our study is to consider the significance of p16 protein expression in relation to clinicopathological parameters and prognosis in patients with oral squamous cell carcinomas. Methods One hundred and twenty patients treated surgically for oral carcinoma were enrolled in the study. The most common anatomical sites of oral carcinoma were the tongue body (54; 45% of cases) and floor of mouth (35; 29.2% of cases). https://www.selleckchem.com/products/conteltinib-ct-707.html All tumours were analysed immunohistochemically for p16 protein expression. The resharyngeal area remains unclear. Intra-abdominal candidiasis (IAC) is an invasive fungal infection representing the most common type of invasive Candida infection in surgical intensive care units (ICUs). Recently, decreased antifungal susceptibility and progressive shift in the aetiology of invasive candidiasis has been observed worldwide. We explored IAC epidemiology in surgical ICU. We retrospectively reviewed the records of 64 patients with IAC admitted at our surgical ICU over a 4-year period (2013-2016). IAC incidence, microbiological results, antifungal therapy, and mortality were analysed. The cumulative IAC incidence was 18.4 cases per 1000 admissions (2013 12.6; 2014 17.7; 2015 16.8; 2016 24.5), including hospital-acquired IAC incidence (2013 9.8; 2014 13.3; 2015 10.1; 2016 13.3) and community-acquired IAC incidence (2013 2.8; 2014 4.4; 2015 6.7; 2016 11.2). Candida albicans represented the most common species (n = 35, 50.0%) followed by Candida glabrata (n = 15, 21.4%), Candida tropicalis (n = 6, 8.6%) and other yeasts (each ogy of IAC towards an increased proportion of non-albicans Candida species, particularly C. glabrata. Acquired decreased fluconazole susceptibility was related to C. glabrata isolates exclusively. Emergence of decreased antifungal susceptibility has been preceded by increase of non-albicans Candida isolates. We have revealed slowly raising of overall IAC incidence, more increasing trend in incidence of community-acquired IAC compared to rather steady incidence of hospital-acquired IAC. During period 2013-2016 we have observed a significant shift in the aetiology of IAC towards an increased proportion of non-albicans Candida species, particularly C. glabrata. Acquired decreased fluconazole susceptibility was related to C. glabrata isolates exclusively. Emergence of decreased antifungal susceptibility has been preceded by increase of non-albicans Candida isolates.Phorbol myristate acetate (PMA)-differentiated THP-1 cells are routinely used in lieu of primary macrophages to study macrophage polarization during host-pathogen interactions and disease progression. The phenotypes of THP-1 macrophages are influenced by the level and duration of PMA stimulation and possibly also by the presence of adhesion factors. Here, we use self-organizing maps (SOMs) of single-cell Raman spectra to probe the effects of PMA stimulation conditions and adhesion factors on THP-1 cell differentiation. Raman spectra encoding for biochemical composition were acquired from individual cells on substrates coated with fibronectin or poly-l-lysine before and after stimulation with 20 or 200 nM PMA for two different time intervals. SOMs constructed from these spectra showed the extent of spectral dissimilarity between different chronological cell populations. For all conditions, the SOMs indicated that the spectra acquired from cells after three-day treatment had diverged from those of untreated cells. The SOMs also showed that the higher PMA concentration produced both fully and partially differentiated cells for both adhesion factors after three days, whereas the outcome of stimulation for three days with the lower PMA concentration depended on the adhesion factor. On poly-l-lysine, treatment with 20 nM PMA for three days induced an intermediate stage of differentiation, but the same treatment produced partially and fully differentiated cells when applied to THP-1 cells on fibronectin. These results are consistent with the modulation of the transition of THP-1 monocytes into macrophage-like cells by integrin-binding interactions. Furthermore, differences in culture and stimulation conditions may confound comparison of results from separate studies.ConspectusCancer immunotherapy, which suppresses tumor relapse and metastasis by boosting host immunity and inducing long-term immune memory effects, is emerging as a vital approach to improve the prognosis of patients. Although remarkable efficacy has been observed in some patients, challenges including low response rate, drug resistance, and immune-related adverse effects still limit the clinical application of cancer immunotherapy in broad types of tumors. Immunotherapeutic agents are used to enhance tumor immunogenicity and reverse the effects of the immunosuppressive tumor microenvironment (ITM), but the benefits of monotherapy are mild and transient due to off-target distribution of drugs. To overcome these issues, smart nanosized drug delivery systems (sNDDS) have been developed to enhance tissue specificity, co-deliver multiple drugs, prime immune cells, and amplify immune responses in tumors. Moreover, accumulating knowledge in cancer biology, immunology, and material science has also greatly promote amplified immunotherapeutic efficacy.Mutagenesis through fast neutron (FN) radiation of soybean resulted in a mutant with a 15% increase in seed protein content. A comparative genomic hybridization analysis confirmed that the mutant is lacking 24 genes located at chromosomes 5 and 10. A tandem mass tag-based proteomic profiling of the wild type and the FN mutant revealed 3,502 proteins, of which 206 proteins exhibited increased abundance and 214 proteins showed decreased abundance. Among the abundant proteins, basic 7S globulin increased fourfold, followed by vacuolar-sorting receptor and protein transporters. The differentially expressed proteins were mapped on the global metabolic pathways. It was observed that there was an enrichment of 29 ribosomal proteins, 16 endoplasmic reticular proteins, and several proteins in export metabolic pathways. The deletion of the sequence-specific DNA binding transcription factor along with 23 other genes may have altered the negative regulation of protein syntheses processes, resulting in an increase in the overall protein content of the mutant seed.0 Comentários 0 Compartilhamentos 197 Visualizações 0 Anterior -
Cardiac arrhythmia, which is an abnormal heart rhythm, is a common clinical problem in cardiology. Detection of arrhythmia on an extended duration electrocardiogram (ECG) is done based on initial algorithmic software screening, with final visual validation by cardiologists. It is a time consuming and subjective process. Therefore, fully automated computer-assisted detection systems with a high degree of accuracy have an essential role in this task. In this study, we proposed an effective deep neural network (DNN) model to detect different rhythm classes from a new ECG database.
Our DNN model was designed for high performance on all ECG leads. The proposed model, which included both representation learning and sequence learning tasks, showed promising results on all 12-lead inputs. Convolutional layers and sub-sampling layers were used in the representation learning phase. The sequence learning part involved a long short-term memory (LSTM) unit after representation of learning layers.
We performed two dilic arrhythmia database comprising more than 10,000 records. We constructed an efficient DNN model for automated detection of arrhythmia using these records.
Cardiovascular diseases are critical diseases and need to be diagnosedas early as possible. There is a lack of medical professionals in remote areas to diagnose these diseases. Artificial intelligence-based automatic diagnostic tools can help to diagnose cardiac diseases. This work presents an automatic classification method using machine learning to diagnose multiple cardiac diseases from phonocardiogram signals.
The proposed system involves a convolutional neural network (CNN) model because of its high accuracy and robustness to automatically diagnose the cardiac disorders from the heart sounds. To improve the accuracy in a noisy environment and make the method robust, the proposed method has used data augmentation techniques for training and multi-classification of multiple cardiac diseases.
The model has been validated both heart sound data and augmented data using n-fold cross-validation. Results of all fold have been shown reported in this work. The model has achieved accuracy on the test set up to 98.60% to diagnose multiple cardiac diseases.
The proposed model can be ported to any computing devices like computers, single board computing processors, android handheld devices etc. To make a stand-alone diagnostic tool that may be of help in remote primary health care centres. The proposed method is non-invasive, efficient, robust, and has low time complexity making it suitable for real-time applications.
The proposed model can be ported to any computing devices like computers, single board computing processors, android handheld devices etc. To make a stand-alone diagnostic tool that may be of help in remote primary health care centres. The proposed method is non-invasive, efficient, robust, and has low time complexity making it suitable for real-time applications.Rhodopsin S334ter-3 retinal degeneration rats have been widely used to investigate degenerative diseases of the retina. In this model, morphological and electrophysiological changes have been observed in the retina, superior colliculus and primary visual cortex (V1). However, no study so far has examined rhodopsin S334ter-3 rats with regards to their contrast response in V1 - a fundamental property of visual information processing. In this study, experimental rats (S334ter-3) carried one copy of the mutant transgene. We compared responses to spatio-temporal variations in luminance contrast in the primary visual cortex of these rats with those in Long-Evans (LE) rats to elucidate the degeneration-specific activity changes in this part of the visual pathway. We measured extracellular responses to different stimulus contrasts at the preferred parameters of each recorded cell under classical receptive field (CRF) stimulation. Our results show that V1 cells in the S334ter-3 group exhibit stronger spontaneous activity but weaker stimulus-evoked responses at medium and high contrasts. By fitting responses to a sigmoid function, we found that the S334ter-3 group had a lower Rmax but a larger exponent N than the LE group. However, we did not find a significant difference in C50 value. These results indicate the decrease in discriminating the stimuli contrast and loss in responses and lower signal to noise ratio after retinal degeneration. Our study supports the notion that a considerable degree of plasticity is found in cortex after retinal degeneration, indicating that visual restoration therapies would succeed if the retina could send useful signals to the brain.The eggs illusion is a visual phenomenon in which bright circular patches located at the midpoints between the intersections of a dark grid are perceived as being elongated along the direction orthogonal to the grid line. In the four experiments we report here, we explored the spatial properties of the eggs illusion by manipulating retinal eccentricity and the location of the stimulus in the visual field. In Experiment 1, we examined whether central and peripheral configurations affected the illusory magnitude. In Experiment 2, we varied the spatial location of grid patterns and found that the eggs illusion was intensified when the pattern was presented in the horizontal, not vertical or diagonal position, relative to the fixation. In Experiment 3, we varied the retinal eccentricity of the pattern along the horizontal meridian and found that the illusion was enhanced in the retinal periphery. https://www.selleckchem.com/products/rmc-6236.html In Experiment 4, we manipulated the size of the stimulus and found that peripheral enhancement of the eggs illusion was more apparent for a larger pattern. The visual field anisotropy and the peripheral enhancement of the eggs illusion are discussed in relation to mechanisms underlying grid-induced illusions.Chemsex among gay, bisexual and other men who have sex with men (GBMSM) has received increasing attention as a public health concern in recent years. Chemsex can affect a variety of aspects of the lives of GBMSM and contribute to physical, social and emotional health burden. Starting from a continuum perspective of chemsex, rather than a binary view of problematic vs. non-problematic use, we argue that men engaging in chemsex at different points in their chemsex journey may benefit from tailored and personalized support to cope with the various and evolving challenges and concerns that may be related to their chemsex behavior. To date, interactive digital communication technologies are not **** used to provide support and care for GBMSM engaging in chemsex, neither for community-based support and care nor by health services. This suggests potential for missed opportunities, as GBMSM are generally avid users of these technologies for social connections and hookups, including in relation to chemsex. Recent research has provided emerging evidence of the potential effects of so-called just in time adaptive interventions (JITAI) to provide effective support and care for a variety of health issues.
Cardiac arrhythmia, which is an abnormal heart rhythm, is a common clinical problem in cardiology. Detection of arrhythmia on an extended duration electrocardiogram (ECG) is done based on initial algorithmic software screening, with final visual validation by cardiologists. It is a time consuming and subjective process. Therefore, fully automated computer-assisted detection systems with a high degree of accuracy have an essential role in this task. In this study, we proposed an effective deep neural network (DNN) model to detect different rhythm classes from a new ECG database. Our DNN model was designed for high performance on all ECG leads. The proposed model, which included both representation learning and sequence learning tasks, showed promising results on all 12-lead inputs. Convolutional layers and sub-sampling layers were used in the representation learning phase. The sequence learning part involved a long short-term memory (LSTM) unit after representation of learning layers. We performed two dilic arrhythmia database comprising more than 10,000 records. We constructed an efficient DNN model for automated detection of arrhythmia using these records. Cardiovascular diseases are critical diseases and need to be diagnosedas early as possible. There is a lack of medical professionals in remote areas to diagnose these diseases. Artificial intelligence-based automatic diagnostic tools can help to diagnose cardiac diseases. This work presents an automatic classification method using machine learning to diagnose multiple cardiac diseases from phonocardiogram signals. The proposed system involves a convolutional neural network (CNN) model because of its high accuracy and robustness to automatically diagnose the cardiac disorders from the heart sounds. To improve the accuracy in a noisy environment and make the method robust, the proposed method has used data augmentation techniques for training and multi-classification of multiple cardiac diseases. The model has been validated both heart sound data and augmented data using n-fold cross-validation. Results of all fold have been shown reported in this work. The model has achieved accuracy on the test set up to 98.60% to diagnose multiple cardiac diseases. The proposed model can be ported to any computing devices like computers, single board computing processors, android handheld devices etc. To make a stand-alone diagnostic tool that may be of help in remote primary health care centres. The proposed method is non-invasive, efficient, robust, and has low time complexity making it suitable for real-time applications. The proposed model can be ported to any computing devices like computers, single board computing processors, android handheld devices etc. To make a stand-alone diagnostic tool that may be of help in remote primary health care centres. The proposed method is non-invasive, efficient, robust, and has low time complexity making it suitable for real-time applications.Rhodopsin S334ter-3 retinal degeneration rats have been widely used to investigate degenerative diseases of the retina. In this model, morphological and electrophysiological changes have been observed in the retina, superior colliculus and primary visual cortex (V1). However, no study so far has examined rhodopsin S334ter-3 rats with regards to their contrast response in V1 - a fundamental property of visual information processing. In this study, experimental rats (S334ter-3) carried one copy of the mutant transgene. We compared responses to spatio-temporal variations in luminance contrast in the primary visual cortex of these rats with those in Long-Evans (LE) rats to elucidate the degeneration-specific activity changes in this part of the visual pathway. We measured extracellular responses to different stimulus contrasts at the preferred parameters of each recorded cell under classical receptive field (CRF) stimulation. Our results show that V1 cells in the S334ter-3 group exhibit stronger spontaneous activity but weaker stimulus-evoked responses at medium and high contrasts. By fitting responses to a sigmoid function, we found that the S334ter-3 group had a lower Rmax but a larger exponent N than the LE group. However, we did not find a significant difference in C50 value. These results indicate the decrease in discriminating the stimuli contrast and loss in responses and lower signal to noise ratio after retinal degeneration. Our study supports the notion that a considerable degree of plasticity is found in cortex after retinal degeneration, indicating that visual restoration therapies would succeed if the retina could send useful signals to the brain.The eggs illusion is a visual phenomenon in which bright circular patches located at the midpoints between the intersections of a dark grid are perceived as being elongated along the direction orthogonal to the grid line. In the four experiments we report here, we explored the spatial properties of the eggs illusion by manipulating retinal eccentricity and the location of the stimulus in the visual field. In Experiment 1, we examined whether central and peripheral configurations affected the illusory magnitude. In Experiment 2, we varied the spatial location of grid patterns and found that the eggs illusion was intensified when the pattern was presented in the horizontal, not vertical or diagonal position, relative to the fixation. In Experiment 3, we varied the retinal eccentricity of the pattern along the horizontal meridian and found that the illusion was enhanced in the retinal periphery. https://www.selleckchem.com/products/rmc-6236.html In Experiment 4, we manipulated the size of the stimulus and found that peripheral enhancement of the eggs illusion was more apparent for a larger pattern. The visual field anisotropy and the peripheral enhancement of the eggs illusion are discussed in relation to mechanisms underlying grid-induced illusions.Chemsex among gay, bisexual and other men who have sex with men (GBMSM) has received increasing attention as a public health concern in recent years. Chemsex can affect a variety of aspects of the lives of GBMSM and contribute to physical, social and emotional health burden. Starting from a continuum perspective of chemsex, rather than a binary view of problematic vs. non-problematic use, we argue that men engaging in chemsex at different points in their chemsex journey may benefit from tailored and personalized support to cope with the various and evolving challenges and concerns that may be related to their chemsex behavior. To date, interactive digital communication technologies are not much used to provide support and care for GBMSM engaging in chemsex, neither for community-based support and care nor by health services. This suggests potential for missed opportunities, as GBMSM are generally avid users of these technologies for social connections and hookups, including in relation to chemsex. Recent research has provided emerging evidence of the potential effects of so-called just in time adaptive interventions (JITAI) to provide effective support and care for a variety of health issues.0 Comentários 0 Compartilhamentos 20 Visualizações 0 Anterior -
Lignin is a potential biomass feedstock from plant material, but it is particularly difficult to economically process. Inspired by recent ball-milling results, state-of-the-art quantum mechanochemistry calculations have been performed to isolate and probe the purely mechanochemical stretching effect alone upon acid-catalyzed deconstruction of lignin. Effects upon cleavage of several exemplary simple ethers are examined first, and with low stretching force they all are predicted to cleave substantially faster, allowing for use of milder acids and lower temperatures. Effects upon an experimentally known lignin fragment model (containing the ubiquitous β-O-4 linkage) are next examined; this first required a mechanism refinement (3-step indirect cleavage, 1-step side reaction) and identification of the rate-limiting step under zero-force (thermal) conditions. Mechanochemical activation using very low stretching forces improves at first only yield, by fully shutting off the ring-closure side reaction. At only somewhat larger forces, in stark contrast, a switch in mechanism is found to occur, from 3-step indirect cleavage to the direct cleavage mechanism of simple ethers, finally strongly enhancing the cleavage rate of lignin. It is concluded that mechanochemical activation of the common β-O-4 link in lignin would improve the rate of its acidolysis via a mechanism switch past a low force threshold. Relevance to ball-milling experiments is discussed.
This study factor analyzes six scales relating to acculturation and related experiences among a nationally representative sample of United States-residing Latina/os (n = 2,541) from the National Latino and Asian American Study (NLAAS), using measurement invariance (MI) testing to explore differences in latent constructs by Latina/o subgroup.
Factor Analysis (FA) within an Exploratory Structural Equation Modeling framework was used to analyze the factor structure of six scales measuring acculturation and related experiences (i.e., acculturation [language use and preference], enculturation [ethnic identity], discrimination, neighborhood context, and family environment). We tested for MI by two important Latina/o subgroups ethnic heritage and generational status.
The underlying latent factors resulting from FA strongly aligned with the NLAAS subscales. No scale achieved full MI, yet the degree to which MI held varied greatly by scale and by subgroup.
Findings show that Latina/os are heterogeneous, but that this often depends on the construct and subgrouping of interest. Future research should use these scales in a latent framework, accounting for the lack of MI, to ensure that the underlying acculturative constructs of interest are validly measured when investigating their association with mental health outcomes in this population.
Findings show that Latina/os are heterogeneous, but that this often depends on the construct and subgrouping of interest. https://www.selleckchem.com/products/ibmx.html Future research should use these scales in a latent framework, accounting for the lack of MI, to ensure that the underlying acculturative constructs of interest are validly measured when investigating their association with mental health outcomes in this population.
To investigate global patterns of cardiovascular risk factor control in patients with type 2 diabetes mellitus (T2D).
DISCOVER is an international, observational cohort study of patients with T2D beginning second-line glucose-lowering therapy. Risk factor management was examined among eligible patients (ie, those with the risk factor) at study baseline. Inter-country variability was estimated using median odds ratios (MORs).
Among 14 343 patients with T2D from 34 countries, the mean age was 57.4 ± 12.0 years and the median (interquartile range) duration of T2D was 4.2 (2.0-8.0) years; 11.8% had documented atherosclerotic cardiovascular disease (ASCVD). Among eligible patients, blood pressure was controlled in 67.5% (9284/13756), statins were prescribed in 43.7% (5775/13208), angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers were prescribed in 55.6% (5292/9512), aspirin was prescribed in 53.3% of those with established ASCVD (876/1645), and 84.4% (12 102/14343) were non-smoking. Only 21.5% of patients (3088/14343) had optimal risk factor management (defined as control of all eligible measures), with wide inter-country variability (10%-44%), even after adjusting for patient and site differences (MOR 1.47, 95% confidence interval 1.24-1.66).
Globally, comprehensive control of ASCVD risk factors is not being achieved in most patients, with wide variability among countries unaccounted for by patient and site differences. Better country-specific strategies are needed to implement comprehensive cardiovascular risk factor control consistently in patients with T2D to improve long-term outcomes.
Globally, comprehensive control of ASCVD risk factors is not being achieved in most patients, with wide variability among countries unaccounted for by patient and site differences. Better country-specific strategies are needed to implement comprehensive cardiovascular risk factor control consistently in patients with T2D to improve long-term outcomes.
In children, vitamin D deficiency is common after renal transplantation. Besides promoting bone and muscle development, vitamin D has immunomodulatory effects, which could protect kidney allografts. The purpose of this study was to assess the association between vitamin D status and the occurrence of renal rejection.
We studied a retrospective cohort of 123 children, who were transplanted at a single institution between September 2008 and April 2019. Patients did not receive vitamin D supplementation systematically. In addition, factors influencing vitamin D status were analyzed using univariate and multivariate analyses.
Median 25-hydroxy-vitamin D (25-OH-D) concentration was close to reference values at the time of transplantation (30ng/mL (min-max 5-100)), but rapidly decreased within the first 3months to 19ng/mL (min-max 3-91) (P<.001). The overall acute rejection rate was 7%. The clinical rejection rate (5% vs 9%), subclinical rejection (12% vs 36%), and borderline changes (21% vs 28%) were not statistically different during the follow-up between the 3-month 25-OH-D<20ng/mL and 3-month 25-OH-D>20ng/mL groups.
Lignin is a potential biomass feedstock from plant material, but it is particularly difficult to economically process. Inspired by recent ball-milling results, state-of-the-art quantum mechanochemistry calculations have been performed to isolate and probe the purely mechanochemical stretching effect alone upon acid-catalyzed deconstruction of lignin. Effects upon cleavage of several exemplary simple ethers are examined first, and with low stretching force they all are predicted to cleave substantially faster, allowing for use of milder acids and lower temperatures. Effects upon an experimentally known lignin fragment model (containing the ubiquitous β-O-4 linkage) are next examined; this first required a mechanism refinement (3-step indirect cleavage, 1-step side reaction) and identification of the rate-limiting step under zero-force (thermal) conditions. Mechanochemical activation using very low stretching forces improves at first only yield, by fully shutting off the ring-closure side reaction. At only somewhat larger forces, in stark contrast, a switch in mechanism is found to occur, from 3-step indirect cleavage to the direct cleavage mechanism of simple ethers, finally strongly enhancing the cleavage rate of lignin. It is concluded that mechanochemical activation of the common β-O-4 link in lignin would improve the rate of its acidolysis via a mechanism switch past a low force threshold. Relevance to ball-milling experiments is discussed. This study factor analyzes six scales relating to acculturation and related experiences among a nationally representative sample of United States-residing Latina/os (n = 2,541) from the National Latino and Asian American Study (NLAAS), using measurement invariance (MI) testing to explore differences in latent constructs by Latina/o subgroup. Factor Analysis (FA) within an Exploratory Structural Equation Modeling framework was used to analyze the factor structure of six scales measuring acculturation and related experiences (i.e., acculturation [language use and preference], enculturation [ethnic identity], discrimination, neighborhood context, and family environment). We tested for MI by two important Latina/o subgroups ethnic heritage and generational status. The underlying latent factors resulting from FA strongly aligned with the NLAAS subscales. No scale achieved full MI, yet the degree to which MI held varied greatly by scale and by subgroup. Findings show that Latina/os are heterogeneous, but that this often depends on the construct and subgrouping of interest. Future research should use these scales in a latent framework, accounting for the lack of MI, to ensure that the underlying acculturative constructs of interest are validly measured when investigating their association with mental health outcomes in this population. Findings show that Latina/os are heterogeneous, but that this often depends on the construct and subgrouping of interest. https://www.selleckchem.com/products/ibmx.html Future research should use these scales in a latent framework, accounting for the lack of MI, to ensure that the underlying acculturative constructs of interest are validly measured when investigating their association with mental health outcomes in this population. To investigate global patterns of cardiovascular risk factor control in patients with type 2 diabetes mellitus (T2D). DISCOVER is an international, observational cohort study of patients with T2D beginning second-line glucose-lowering therapy. Risk factor management was examined among eligible patients (ie, those with the risk factor) at study baseline. Inter-country variability was estimated using median odds ratios (MORs). Among 14 343 patients with T2D from 34 countries, the mean age was 57.4 ± 12.0 years and the median (interquartile range) duration of T2D was 4.2 (2.0-8.0) years; 11.8% had documented atherosclerotic cardiovascular disease (ASCVD). Among eligible patients, blood pressure was controlled in 67.5% (9284/13756), statins were prescribed in 43.7% (5775/13208), angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers were prescribed in 55.6% (5292/9512), aspirin was prescribed in 53.3% of those with established ASCVD (876/1645), and 84.4% (12 102/14343) were non-smoking. Only 21.5% of patients (3088/14343) had optimal risk factor management (defined as control of all eligible measures), with wide inter-country variability (10%-44%), even after adjusting for patient and site differences (MOR 1.47, 95% confidence interval 1.24-1.66). Globally, comprehensive control of ASCVD risk factors is not being achieved in most patients, with wide variability among countries unaccounted for by patient and site differences. Better country-specific strategies are needed to implement comprehensive cardiovascular risk factor control consistently in patients with T2D to improve long-term outcomes. Globally, comprehensive control of ASCVD risk factors is not being achieved in most patients, with wide variability among countries unaccounted for by patient and site differences. Better country-specific strategies are needed to implement comprehensive cardiovascular risk factor control consistently in patients with T2D to improve long-term outcomes. In children, vitamin D deficiency is common after renal transplantation. Besides promoting bone and muscle development, vitamin D has immunomodulatory effects, which could protect kidney allografts. The purpose of this study was to assess the association between vitamin D status and the occurrence of renal rejection. We studied a retrospective cohort of 123 children, who were transplanted at a single institution between September 2008 and April 2019. Patients did not receive vitamin D supplementation systematically. In addition, factors influencing vitamin D status were analyzed using univariate and multivariate analyses. Median 25-hydroxy-vitamin D (25-OH-D) concentration was close to reference values at the time of transplantation (30ng/mL (min-max 5-100)), but rapidly decreased within the first 3months to 19ng/mL (min-max 3-91) (P<.001). The overall acute rejection rate was 7%. The clinical rejection rate (5% vs 9%), subclinical rejection (12% vs 36%), and borderline changes (21% vs 28%) were not statistically different during the follow-up between the 3-month 25-OH-D<20ng/mL and 3-month 25-OH-D>20ng/mL groups.0 Comentários 0 Compartilhamentos 20 Visualizações 0 Anterior -
t existing literature about modeling strategies against the virus to help modelers to navigate this fast-growing literature. We also keep an eye on future outbreaks, where the modelers can find the most relevant strategies used in an emergency situation as the current one to help in fighting future pandemics.Social media has enhanced integration between marketing and public relations. As such, public relations professionals have had to adapt and grow their knowledge and skillsets to stay relevant and current throughout the evolution of the digital landscape (Gesualdi, 2019). One of the growing areas of focus for public relations professionals has been customer service skills online. This specialization, often referred to as social care or social customer service, has been promoted and discussed heavily in industry circles and publications, but not in academic research. This study focuses on the survey results from 396 employers exploring the social media skills they most prefer university graduates to possess when entering the workforce. The results indicate that public relations and customer service are the social media skills most sought after by employers of university graduates ahead of proficiency in areas such as social media content production, strategy development and analytics. The potential implications of these findings to the public relations profession are examined and future research is also discussed.Dialogic communication has long been viewed as vital for effective organization-public relations. Yet, it is under-theorized whether and how organizations' disaster communication messages may embody dialogic communication principles, and how various dialogic features are associated with different public engagement outcomes on social media. Extending the Organization-Public Dialogic Communication (OPDC) framework to the context of social media-mediated disaster communication, we propose a multi-level framework to assess the dialogic capacity of Facebook messages sent by disaster management organizations during a natural disaster. Three levels of dialogic communication characteristics (i.e., message structure-level, topic-level, and linguistic level) are examined using content analysis and Linguistic Inquiry and Word Count (LIWC). Results identified media richness, correcting, and confirming topics as three consistent predictors of public engagement of all types. Meanwhile, there exhibit greater variations regarding how other topical features and linguistic characteristics are related to public's cognitive, emotional, and behavioral engagement during a disaster.Ant Colony algorithm has been applied to various optimisation problems, however, most of the previous work on scaling and parallelism focuses on Travelling Salesman Problems (TSPs). Although useful for benchmarks and new idea comparison, the algorithmic dynamics do not always transfer to complex real-life problems, where additional meta-data is required during solution construction. This paper explores how the benchmark performance differs from real-world problems in the context of Ant Colony Optimization (ACO) and demonstrate that in order to generalise the findings, the algorithms have to be tested on both standard benchmarks and real-world applications. ACO and its scaling dynamics with two parallel ACO architectures - Independent Ant Colonies (IAC) and Parallel Ants (PA). Results showed that PA was able to reach a higher solution quality in fewer iterations as the number of parallel instances increased. Furthermore, speed performance was measured across three different hardware solutions - 16 core CPU, 68 core Xeon Phi and up to 4 Geforce GPUs. State of the art, ACO vectorisation techniques such as SS-Roulette were implemented using C++ and CUDA. Although excellent for routing simple TSPs, it was concluded that for complex real-world supply chain routing GPUs are not suitable due to meta-data access footprint required. Thus, our work demonstrates that the standard benchmarks are not suitable for generalised conclusions.The Coverage Location Problem (CLP) seeks the best locations for service to minimize the total number of facilities required to meet all demands. This paper studies a new variation of this problem, called the Coverage Location Problem with Overlap Control (CLPOC). This problem models real contexts related to overloaded attendance systems, which require coverage zones with overlaps. Thus, each demand must be covered by a certain number of additional facilities to ensure that demands will be met even when the designated facility is unable to due to some facility issue. This feature is important in public and emergency services. We observe that this number of additional facilities is excessive in some demand points because overlaps among coverage zones occur naturally in CLP. The goal of the CLPOC is to control overlaps to prioritize regions with a high density population or to minimize the number of coverage zones for each demand point. In this paper, we propose a new mathematical model for the CLPOC that controls the overlap between coverage zones. https://www.selleckchem.com/products/resiquimod.html We used a commercial solver to find the optimal solutions for available instances in the literature. The computational tests show that the proposed mathematical model found appropriate solutions in terms of number of demand points with minimum coverage zones and sufficient coverage zones for high demand points.Thermoelectric radiant panel system (TERP), requires no hydronic pipes, pumps and chillers and the size is compact in solid form. In this study, the main results include a new system model of TERP and some new findings on the system dynamic characteristics. The new model integrates finite difference method and state-space matrix, which is an integration of great simulation accuracy, high speed, and easy implementation. The thermal response time (TRT) and its asynchronism are confirmed and a new concept of AM (Asynchronism Magnitude) is defined to measure the degree of TRT asynchronism. Some new observations are obtained (1) Under a certain environment, AM becomes a constant even when different step changes of current are imposed; (2) The TRT asynchronism disappeared at the second stage when environmental condition is step changed. Three new definitions of TRT are proposed and compared. Finally, in order to realize the fast and accurate prediction of TRT for the use of system on-line control or fast evaluation under dynamic state, an artificial neural network-based model is proved to be effective.
t existing literature about modeling strategies against the virus to help modelers to navigate this fast-growing literature. We also keep an eye on future outbreaks, where the modelers can find the most relevant strategies used in an emergency situation as the current one to help in fighting future pandemics.Social media has enhanced integration between marketing and public relations. As such, public relations professionals have had to adapt and grow their knowledge and skillsets to stay relevant and current throughout the evolution of the digital landscape (Gesualdi, 2019). One of the growing areas of focus for public relations professionals has been customer service skills online. This specialization, often referred to as social care or social customer service, has been promoted and discussed heavily in industry circles and publications, but not in academic research. This study focuses on the survey results from 396 employers exploring the social media skills they most prefer university graduates to possess when entering the workforce. The results indicate that public relations and customer service are the social media skills most sought after by employers of university graduates ahead of proficiency in areas such as social media content production, strategy development and analytics. The potential implications of these findings to the public relations profession are examined and future research is also discussed.Dialogic communication has long been viewed as vital for effective organization-public relations. Yet, it is under-theorized whether and how organizations' disaster communication messages may embody dialogic communication principles, and how various dialogic features are associated with different public engagement outcomes on social media. Extending the Organization-Public Dialogic Communication (OPDC) framework to the context of social media-mediated disaster communication, we propose a multi-level framework to assess the dialogic capacity of Facebook messages sent by disaster management organizations during a natural disaster. Three levels of dialogic communication characteristics (i.e., message structure-level, topic-level, and linguistic level) are examined using content analysis and Linguistic Inquiry and Word Count (LIWC). Results identified media richness, correcting, and confirming topics as three consistent predictors of public engagement of all types. Meanwhile, there exhibit greater variations regarding how other topical features and linguistic characteristics are related to public's cognitive, emotional, and behavioral engagement during a disaster.Ant Colony algorithm has been applied to various optimisation problems, however, most of the previous work on scaling and parallelism focuses on Travelling Salesman Problems (TSPs). Although useful for benchmarks and new idea comparison, the algorithmic dynamics do not always transfer to complex real-life problems, where additional meta-data is required during solution construction. This paper explores how the benchmark performance differs from real-world problems in the context of Ant Colony Optimization (ACO) and demonstrate that in order to generalise the findings, the algorithms have to be tested on both standard benchmarks and real-world applications. ACO and its scaling dynamics with two parallel ACO architectures - Independent Ant Colonies (IAC) and Parallel Ants (PA). Results showed that PA was able to reach a higher solution quality in fewer iterations as the number of parallel instances increased. Furthermore, speed performance was measured across three different hardware solutions - 16 core CPU, 68 core Xeon Phi and up to 4 Geforce GPUs. State of the art, ACO vectorisation techniques such as SS-Roulette were implemented using C++ and CUDA. Although excellent for routing simple TSPs, it was concluded that for complex real-world supply chain routing GPUs are not suitable due to meta-data access footprint required. Thus, our work demonstrates that the standard benchmarks are not suitable for generalised conclusions.The Coverage Location Problem (CLP) seeks the best locations for service to minimize the total number of facilities required to meet all demands. This paper studies a new variation of this problem, called the Coverage Location Problem with Overlap Control (CLPOC). This problem models real contexts related to overloaded attendance systems, which require coverage zones with overlaps. Thus, each demand must be covered by a certain number of additional facilities to ensure that demands will be met even when the designated facility is unable to due to some facility issue. This feature is important in public and emergency services. We observe that this number of additional facilities is excessive in some demand points because overlaps among coverage zones occur naturally in CLP. The goal of the CLPOC is to control overlaps to prioritize regions with a high density population or to minimize the number of coverage zones for each demand point. In this paper, we propose a new mathematical model for the CLPOC that controls the overlap between coverage zones. https://www.selleckchem.com/products/resiquimod.html We used a commercial solver to find the optimal solutions for available instances in the literature. The computational tests show that the proposed mathematical model found appropriate solutions in terms of number of demand points with minimum coverage zones and sufficient coverage zones for high demand points.Thermoelectric radiant panel system (TERP), requires no hydronic pipes, pumps and chillers and the size is compact in solid form. In this study, the main results include a new system model of TERP and some new findings on the system dynamic characteristics. The new model integrates finite difference method and state-space matrix, which is an integration of great simulation accuracy, high speed, and easy implementation. The thermal response time (TRT) and its asynchronism are confirmed and a new concept of AM (Asynchronism Magnitude) is defined to measure the degree of TRT asynchronism. Some new observations are obtained (1) Under a certain environment, AM becomes a constant even when different step changes of current are imposed; (2) The TRT asynchronism disappeared at the second stage when environmental condition is step changed. Three new definitions of TRT are proposed and compared. Finally, in order to realize the fast and accurate prediction of TRT for the use of system on-line control or fast evaluation under dynamic state, an artificial neural network-based model is proved to be effective.0 Comentários 0 Compartilhamentos 219 Visualizações 0 Anterior
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