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  • nditions demonstrating the still huge potential for the development of promising stent solutions.The inhibition of the aberrant differentiation of tendon-derived stem cells (TDSCs) is a major target for the regeneration of damaged tendon tissues, as tendinopathy can be caused by the aberrant differentiation of TDSCs. https://www.selleckchem.com/products/Staurosporine.html We investigated whether the possible aberrant differentiation of TDSCs can be prevented by using adequate inhibitors. TDSCs extracted from chemically induced tendinopathy and injury-with-overuse tendinopathy models were cultured with 18α-glycyrrhetinic acid (AGA) and T0070907 to block osteogenic differentiation and adipogenic differentiation, respectively. The optimal dose of AGA decreased the osteogenic-specific marker Runx2 (Runt-related transcription factor 2), and T0070907 blocked the adipogenic-specific marker peroxisome proliferator-activated receptor gamma (PPARγ) in mRNA levels. We also found that AGA induced tenogenic differentiation in mRNA levels. However, T0070907 did not affect the tenogenic differentiation and regenerative capacity of TDSCs. We expect that optimal doses of AGA and T0070907 can prevent tendinopathy by inhibiting osteogenic and adipogenic differentiation, respectively. In addition, AGA and T0070907 may play important roles in the treatment of tendinopathy.Kidney diseases form part of the major health burdens experienced all over the world. Kidney diseases are linked to high economic burden, deaths, and morbidity rates. The great importance of collecting a large quantity of health-related data among human cohorts, what scholars refer to as "big data", has increasingly been identified, with the establishment of a large group of cohorts and the usage of electronic health records (EHRs) in nephrology and transplantation. These data are valuable, and can potentially be utilized by researchers to advance knowledge in the field. Furthermore, progress in big data is stimulating the flourishing of artificial intelligence (AI), which is an excellent tool for handling, and subsequently processing, a great amount of data and may be applied to highlight more information on the effectiveness of medicine in kidney-related complications for the purpose of more precise phenotype and outcome prediction. In this article, we discuss the advances and challenges in big data, the use of EHRs and AI, with great emphasis on the usage of nephrology and transplantation.This observational study aimed to examine the extent of early invasive strategy (EIS) utilization in patients with non-ST elevation acute coronary syndrome (NSTE-ACS) according to the National Cardiovascular Data Registry (NCDR) CathPCI risk score, and its association with clinical outcomes. Using a prospective multicenter Japanese registry, 2968 patients with NSTE-ACS undergoing percutaneous coronary intervention within 72 hours of hospital arrival were analyzed. Multivariable logistic regression analyses were performed to determine predictors of EIS utilization. Additionally, adverse outcomes were compared between patients treated with and without EIS. Overall, 82.1% of the cohort (n = 2436) were treated with EIS, and the median NCDR CathPCI risk score was 22 (interquartile range 14-32) with an expected 0.3-0.6% in-hospital mortality. Advanced age, peripheral artery disease, chronic kidney disease or patients without elevation of cardiac biomarkers were less likely to be treated with EIS. EIS utilization was not associated with a risk of in-hospital mortality; yet, it was associated with an increased risk of acute kidney injury (AKI) (adjusted odds ratio 1.42; 95% confidence interval 1.02-2.01) regardless of patients' in-hospital mortality risk. Broader use of EIS utilization comes at the cost of increased AKI development risk; thus, the pre-procedural risk-benefit profile of EIS should be reassessed appropriately in patients with lower mortality risk.Osteochondromas are cartilage-capped growths located proximate to the physis that can cause skeletal deformities, pain, limited motion, and neurovascular impingement. Previous studies have demonstrated retinoic acid receptor gamma (RARγ) agonists to inhibit ectopic endochondral ossification, therefore we hypothesize that RARγ agonists can target on established osteochondromas. The purpose of this study was to examine the action of RARγ agonist in human osteochondromas. Osteochondroma specimens were obtained during surgery, subjected to explant culture and were treated with RARγ agonists or vehicles. Gene expression analysis confirmed the up-regulation of RARγ target genes in the explants treated with NRX 204647 and Palovarotene and revealed strong inhibition of cartilage matrix and increased extracellular matrix proteases gene expression. In addition, immunohistochemical staining for the neoepitope of protease-cleaved aggrecan indicated that RARγ agonist treatment stimulated cartilage matrix degradation. Interestingly, cell survival studies demonstrated that RARγ agonist treatment stimulated cell death. Moreover, RNA sequencing analysis indicates changes in multiple molecular pathways due to RARγ agonists treatment, showing similarly to human growth plate chondrocytes. Together, these findings suggest that RARγ agonist may exert anti-tumor function on osteochondromas by inhibiting matrix synthesis, promoting cartilage matrix degradation and stimulating cell death.Medetomidine has been reported to decrease tear flow significantly in dogs, cats, and pigs when used as a sedative or analgesic; however, there are no such reports when it comes to rats. The present study aimed to investigate the effect of medetomidine on tear flow in rats. Medetomidine in doses of 50, 100, or 200 µg/kg or a physiological saline solution as the control, were administered intramuscularly to male SlcWistar/ST rats. After the administration of medetomidine, tear flow in both eyes was measured using a phenol red thread tear test. The area under the curve (AUC) of phenol red thread test values from baseline to 8 h was calculated. Data were plotted against the dose of medetomidine and simple linear regression analysis was performed. The effect of the drug on phenol red thread test values was considered dose-related when linear analysis yielded a significant relationship. In all medetomidine-treated groups, tear flow decreased significantly in both eyes after administration, while no significant changes were observed in either eye in the control group.
    nditions demonstrating the still huge potential for the development of promising stent solutions.The inhibition of the aberrant differentiation of tendon-derived stem cells (TDSCs) is a major target for the regeneration of damaged tendon tissues, as tendinopathy can be caused by the aberrant differentiation of TDSCs. https://www.selleckchem.com/products/Staurosporine.html We investigated whether the possible aberrant differentiation of TDSCs can be prevented by using adequate inhibitors. TDSCs extracted from chemically induced tendinopathy and injury-with-overuse tendinopathy models were cultured with 18α-glycyrrhetinic acid (AGA) and T0070907 to block osteogenic differentiation and adipogenic differentiation, respectively. The optimal dose of AGA decreased the osteogenic-specific marker Runx2 (Runt-related transcription factor 2), and T0070907 blocked the adipogenic-specific marker peroxisome proliferator-activated receptor gamma (PPARγ) in mRNA levels. We also found that AGA induced tenogenic differentiation in mRNA levels. However, T0070907 did not affect the tenogenic differentiation and regenerative capacity of TDSCs. We expect that optimal doses of AGA and T0070907 can prevent tendinopathy by inhibiting osteogenic and adipogenic differentiation, respectively. In addition, AGA and T0070907 may play important roles in the treatment of tendinopathy.Kidney diseases form part of the major health burdens experienced all over the world. Kidney diseases are linked to high economic burden, deaths, and morbidity rates. The great importance of collecting a large quantity of health-related data among human cohorts, what scholars refer to as "big data", has increasingly been identified, with the establishment of a large group of cohorts and the usage of electronic health records (EHRs) in nephrology and transplantation. These data are valuable, and can potentially be utilized by researchers to advance knowledge in the field. Furthermore, progress in big data is stimulating the flourishing of artificial intelligence (AI), which is an excellent tool for handling, and subsequently processing, a great amount of data and may be applied to highlight more information on the effectiveness of medicine in kidney-related complications for the purpose of more precise phenotype and outcome prediction. In this article, we discuss the advances and challenges in big data, the use of EHRs and AI, with great emphasis on the usage of nephrology and transplantation.This observational study aimed to examine the extent of early invasive strategy (EIS) utilization in patients with non-ST elevation acute coronary syndrome (NSTE-ACS) according to the National Cardiovascular Data Registry (NCDR) CathPCI risk score, and its association with clinical outcomes. Using a prospective multicenter Japanese registry, 2968 patients with NSTE-ACS undergoing percutaneous coronary intervention within 72 hours of hospital arrival were analyzed. Multivariable logistic regression analyses were performed to determine predictors of EIS utilization. Additionally, adverse outcomes were compared between patients treated with and without EIS. Overall, 82.1% of the cohort (n = 2436) were treated with EIS, and the median NCDR CathPCI risk score was 22 (interquartile range 14-32) with an expected 0.3-0.6% in-hospital mortality. Advanced age, peripheral artery disease, chronic kidney disease or patients without elevation of cardiac biomarkers were less likely to be treated with EIS. EIS utilization was not associated with a risk of in-hospital mortality; yet, it was associated with an increased risk of acute kidney injury (AKI) (adjusted odds ratio 1.42; 95% confidence interval 1.02-2.01) regardless of patients' in-hospital mortality risk. Broader use of EIS utilization comes at the cost of increased AKI development risk; thus, the pre-procedural risk-benefit profile of EIS should be reassessed appropriately in patients with lower mortality risk.Osteochondromas are cartilage-capped growths located proximate to the physis that can cause skeletal deformities, pain, limited motion, and neurovascular impingement. Previous studies have demonstrated retinoic acid receptor gamma (RARγ) agonists to inhibit ectopic endochondral ossification, therefore we hypothesize that RARγ agonists can target on established osteochondromas. The purpose of this study was to examine the action of RARγ agonist in human osteochondromas. Osteochondroma specimens were obtained during surgery, subjected to explant culture and were treated with RARγ agonists or vehicles. Gene expression analysis confirmed the up-regulation of RARγ target genes in the explants treated with NRX 204647 and Palovarotene and revealed strong inhibition of cartilage matrix and increased extracellular matrix proteases gene expression. In addition, immunohistochemical staining for the neoepitope of protease-cleaved aggrecan indicated that RARγ agonist treatment stimulated cartilage matrix degradation. Interestingly, cell survival studies demonstrated that RARγ agonist treatment stimulated cell death. Moreover, RNA sequencing analysis indicates changes in multiple molecular pathways due to RARγ agonists treatment, showing similarly to human growth plate chondrocytes. Together, these findings suggest that RARγ agonist may exert anti-tumor function on osteochondromas by inhibiting matrix synthesis, promoting cartilage matrix degradation and stimulating cell death.Medetomidine has been reported to decrease tear flow significantly in dogs, cats, and pigs when used as a sedative or analgesic; however, there are no such reports when it comes to rats. The present study aimed to investigate the effect of medetomidine on tear flow in rats. Medetomidine in doses of 50, 100, or 200 µg/kg or a physiological saline solution as the control, were administered intramuscularly to male SlcWistar/ST rats. After the administration of medetomidine, tear flow in both eyes was measured using a phenol red thread tear test. The area under the curve (AUC) of phenol red thread test values from baseline to 8 h was calculated. Data were plotted against the dose of medetomidine and simple linear regression analysis was performed. The effect of the drug on phenol red thread test values was considered dose-related when linear analysis yielded a significant relationship. In all medetomidine-treated groups, tear flow decreased significantly in both eyes after administration, while no significant changes were observed in either eye in the control group.
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  • случаев и безопасным методом лечения детей, страдающих рецидивирующим течением экссудативного среднего отита.in English, Russian Врачу-педиатру в своей практике приходится достаточно часто встречаться с различной оториноларингологической патологией, т.к. более половины обращений в детские поликлиники связано с заболеваниями лор-органов. В представленной статье освещены вопросы внедрения методов диагностики и лечения острой и хронической патологии лор-органов в практику врачей-педиатров.in English, Russian Обобщены литературные и собственные данные о роли вирусов и других патогенов в этиологии инфекционных и неинфекционных увеитов. Инфекционные увеиты обусловлены активной интраокулярной репликацией вируса (герпесвирусные, острая стадия энтеровирусных) либо их длительной персистенцией в тканях глаза (синдром Фукса, ассоциированный с вирусом краснухи, поздние осложнения энтеровирусных увеитов). Клиническая картина, тяжесть, исходы инфекционных увеитов зависят от возбудителя, адекватности иммунного ответа и генетических особенностей пациента. Многие неинфекционные увеиты относятся к иммуноопосредованным, в инициации которых важную роль играют инфекции. Механизмы реализации триггерных функций инфекций включают антигенную мимикрию, неспецифическую активацию, распространение эпитопа, наличие суперантигенов, влияние микробиоты кишечника. Неконтролируемый, чрезмерный иммунный ответ хозяина способствует деструкции клеток даже после удаления инфекции.in English, Russian Эндотелиновая система (ЭС) как локальный регулятор не только сосудистого тонуса, но многих других физиологических процессов играет многогранную роль в патогенезе целого ряда глазных болезней. Компоненты ЭС - эндотелины и их рецепторы - обнаружены практически во всех клеточных структурах глаза, и их содержание возрастает при многих глазных болезнях. При глаукоме ЭС участвует в механизмах повышения уровня внутриглазного давления (ВГД) путем влияния как на отток, так и на образование внутриглазной жидкости. Увеличение содержания эндотелина приводит к снижению перфузионного давления, гипоксии, пролиферации астроцитов, повышению плотности и ригидности решетчатой пластинки, апоптозу нервных клеток, оказывает профиброгенное действие. https://www.selleckchem.com/products/GDC-0449.html При патологии сетчатки увеличение содержания эндотелина нарушает процессы ауторегуляции сосудов сетчатки путем влияния на нейроваскулярные взаимодействия, нарушает межклеточные контакты в сетчатке, способствует ангиогенезу. При диабетической ретинопатии ЭС участвует в развитии микроангиопатий и пролиферативной витреоретинопатии. Обсуждается возможность медикаментозной коррекции активности ЭС в глазу путем воздействия на синтез, распад и взаимодействие эндотелинов с различными рецепторами.in English, Russian Статья содержит описание принципа 'swept source' - оптической когерентной томографии (SS-ОКТ). Изложены краткая история создания технологии, способы ее реализации в современных коммерческих томографах, преимущества и недостатки.in English, Russian Применение атомно-силовой микроскопии (АСМ) в офтальмологии предполагает два основных направления в соответствии с классическим анатомическим делением глазного яблока на передний и задний сегменты. В настоящем обзоре представлены результаты опубликованных работ, в которых АСМ использовали для анатомо-функционального изучения структур переднего сегмента глаза. Достаточно большой по объему блок исследований связан с применением АСМ-технологий для оценки морфологических и биомеханических особенностей различных отделов хрусталика. Интерес к данной проблеме, с одной стороны, продиктован необходимостью дальнейшего изучения процессов катарактогенеза, а с другой - анатомо-функциональной значимостью капсулы хрусталика в механизме аккомодации и современной факохирургии.
    случаев и безопасным методом лечения детей, страдающих рецидивирующим течением экссудативного среднего отита.in English, Russian Врачу-педиатру в своей практике приходится достаточно часто встречаться с различной оториноларингологической патологией, т.к. более половины обращений в детские поликлиники связано с заболеваниями лор-органов. В представленной статье освещены вопросы внедрения методов диагностики и лечения острой и хронической патологии лор-органов в практику врачей-педиатров.in English, Russian Обобщены литературные и собственные данные о роли вирусов и других патогенов в этиологии инфекционных и неинфекционных увеитов. Инфекционные увеиты обусловлены активной интраокулярной репликацией вируса (герпесвирусные, острая стадия энтеровирусных) либо их длительной персистенцией в тканях глаза (синдром Фукса, ассоциированный с вирусом краснухи, поздние осложнения энтеровирусных увеитов). Клиническая картина, тяжесть, исходы инфекционных увеитов зависят от возбудителя, адекватности иммунного ответа и генетических особенностей пациента. Многие неинфекционные увеиты относятся к иммуноопосредованным, в инициации которых важную роль играют инфекции. Механизмы реализации триггерных функций инфекций включают антигенную мимикрию, неспецифическую активацию, распространение эпитопа, наличие суперантигенов, влияние микробиоты кишечника. Неконтролируемый, чрезмерный иммунный ответ хозяина способствует деструкции клеток даже после удаления инфекции.in English, Russian Эндотелиновая система (ЭС) как локальный регулятор не только сосудистого тонуса, но многих других физиологических процессов играет многогранную роль в патогенезе целого ряда глазных болезней. Компоненты ЭС - эндотелины и их рецепторы - обнаружены практически во всех клеточных структурах глаза, и их содержание возрастает при многих глазных болезнях. При глаукоме ЭС участвует в механизмах повышения уровня внутриглазного давления (ВГД) путем влияния как на отток, так и на образование внутриглазной жидкости. Увеличение содержания эндотелина приводит к снижению перфузионного давления, гипоксии, пролиферации астроцитов, повышению плотности и ригидности решетчатой пластинки, апоптозу нервных клеток, оказывает профиброгенное действие. https://www.selleckchem.com/products/GDC-0449.html При патологии сетчатки увеличение содержания эндотелина нарушает процессы ауторегуляции сосудов сетчатки путем влияния на нейроваскулярные взаимодействия, нарушает межклеточные контакты в сетчатке, способствует ангиогенезу. При диабетической ретинопатии ЭС участвует в развитии микроангиопатий и пролиферативной витреоретинопатии. Обсуждается возможность медикаментозной коррекции активности ЭС в глазу путем воздействия на синтез, распад и взаимодействие эндотелинов с различными рецепторами.in English, Russian Статья содержит описание принципа 'swept source' - оптической когерентной томографии (SS-ОКТ). Изложены краткая история создания технологии, способы ее реализации в современных коммерческих томографах, преимущества и недостатки.in English, Russian Применение атомно-силовой микроскопии (АСМ) в офтальмологии предполагает два основных направления в соответствии с классическим анатомическим делением глазного яблока на передний и задний сегменты. В настоящем обзоре представлены результаты опубликованных работ, в которых АСМ использовали для анатомо-функционального изучения структур переднего сегмента глаза. Достаточно большой по объему блок исследований связан с применением АСМ-технологий для оценки морфологических и биомеханических особенностей различных отделов хрусталика. Интерес к данной проблеме, с одной стороны, продиктован необходимостью дальнейшего изучения процессов катарактогенеза, а с другой - анатомо-функциональной значимостью капсулы хрусталика в механизме аккомодации и современной факохирургии.
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  • We discover that analysis in the frozen-hydrated state yields a 10,000 fold increase in signal intensity for polar molecules, such as amino acid, which has important implications for SIMS imaging of metabolites and pharmaceuticals.Optically triggered twisted intramolecular charge transfer (TICT) states in donor-acceptor chromophores form the molecular basis for designing bioimaging probes that sense polarity, microviscosity, and pH in vivo. However, a lack of predictive understanding of the "twist" localization precludes a rational design of TICT-based dyes. Here, using femtosecond stimulated Raman spectroscopy, we reveal a distinct Raman signature of the TICT state for a stilbazolium-class mitochondrial staining dye. Resonance-selective probing of 4-N,N-diethylamino-4″-N'-methyl-stilbazolium tosylate (DEST) tracks the excited-state structure of the dye as it relaxes to a TICT state on a picosecond time scale. The appearance of a remarkably blue-shifted C=C stretching mode at 1650 cm-1 in the TICT state is attributed to the "twist" of a single bond adjacent to the ethylenic π-bridge in the DEST backbone based on detailed electronic structure calculations and vibrational mode analysis. Our work demonstrates that the π-bridge, connecting the donor and acceptor moieties, influences the spatial location of the "twist" and offers a new perspective for designing organelle-specific probes through cogent tuning of backbone dynamics.Enzymes are an important class of biomacromolecules which catalyze many metabolic processes in living systems. Nanomaterials can be synthesized with tailored sizes as well as desired surface modifications, thus acting as promising enzyme regulators. Fluorescent gold nanoclusters (AuNCs) are a representative class of ultrasmall nanoparticles (USNPs) with sizes of ∼2 nm, smaller than most of proteins including enzymes. In this work, we chose α-chymotrypsin (ChT) and AuNCs as the model system. Activity assays and inhibition kinetics studies showed that dihydrolipoic acid (DHLA)-coated AuNCs (DHLA-AuNCs) had a high inhibitory potency (IC50 = 3.4 μM) and high inhibitory efficacy (>80%) on ChT activity through noncompetitive inhibition mechanism. In distinct contrast, glutathione (GSH)-coated AuNCs (GSH-AuNCs) had no significant inhibition effects. Fluorescence spectroscopy, agarose gel electrophoresis and circular dichroism (CD) spectroscopy were conducted to explore the underlying mechanisms. A two-step interaction model was proposed. First, both DHLA-AuNCs and GSH-AuNCs might be bound to the positively charged sites of ChT through electrostatic forces. Second, further hydrophobic interactions occurred between three tyrosine residues of ChT and the hydrophobic carbon chain of DHLA, leading to a significant structural change thus to deactivate ChT on the allosteric site. On the contrary, no such interactions occurred with GSH of zwitterionic characteristic, which explained no inhibitory effect of GSH-AuNCs on ChT. To the best of our knowledge, this is the first example of the allosteric inhibition of ChT by nano regulators. These findings provide a fundamental basis for the design and development of nano regulators.SHP2 (Src homology-2 domain-containing protein tyrosine phosphatase-2) is a non-receptor protein tyrosine phosphatase that removes tyrosine phosphorylation. Functionally, SHP2 serves as an important hub to connect several intracellular oncogenic signaling pathways, such as Jak/STAT, PI3K/AKT, RAS/Raf/MAPK, and PD-1/PD-L1 pathways. https://www.selleckchem.com/products/danicopan.html Mutations and/or overexpression of SHP2 have been associated with genetic developmental diseases and cancers. Because of the role of SHP2 plays in many diseases, the development of inhibitors targeting the catalytic site in SHP2 has been pursued for more than a decade, but none has advanced to clinical development. Recent discovery of allosteric inhibitors has inspired a novel approach to selectively target SHP2 via the non-catalytic site. To date, four SHP2 allosteric inhibitors have entered clinical trials for the treatment of solid tumors. This review will provide a summary of the physiological and biological functions of SHP2 and discuss the development of non-allosteric/allosteric SHP2 inhibitors in recent years.The development of new routes or materials to realize superlubricity under high contact pressure can result in energy-saving and reduction of emissions. In this study, superlubricity (μ = 0.0017) under extreme pressure (717 MPa, more than twice the previously reported liquid superlubricity) between the frictional pair of Si3N4/sapphire was achieved by prerunning-in with a H3PO4 (HP) solution followed by lubrication with an aqueous solution consisting of poly(vinyl alcohol) (PVA) and sodium chloride (NaCl). Under the same test condition, the aqueous PVA lubricant did not show superlubricity. Results of X-ray photoelectron spectroscopy and Raman spectroscopy indicate the formation of a PVA-adsorbed film at the frictional interface after lubrication with PVA but not after lubrication with PVA/NaCl, indicating competitive adsorption between hydrated Na+ ions and PVA molecules. The hydrated Na+ ions adsorbed preferentially to the solid surfaces, causing the transformation of the shear interface from a polymer film/polymer film to a solid/polymer film. Meanwhile, the hydrated Na+ ions also produced hydration repulsion force and induced low shear stress between the solid surfaces. Furthermore, NaCl increased the viscosity of the polymer lubricant, enhanced the hydrodynamic effect between interfaces, and decreased direct contact between the friction pair, causing a further reduction in friction. Thus, the superlubricity of the PVA/NaCl mixture is attributed to the combination of hydration and hydrodynamic effects. This study provides a novel route and mechanism for achieving extreme-pressure superlubricity at the macroscale, through the synergistic lubricating effect of hydrated ions and a polymer solution, propelling the industrial application of superlubricity.A dipyrrin-supported nickel catalyst (AdFL)Ni(py) (AdFL 1,9-di(1-adamantyl)-5-perfluorophenyldipyrrin; py pyridine) displays productive intramolecular C-H bond amination to afford N-heterocyclic products using aliphatic azide substrates. The catalytic amination conditions are mild, requiring 0.1-2 mol% catalyst loading and operational at room temperature. The scope of C-H bond substrates was explored and benzylic, tertiary, secondary, and primary C-H bonds are successfully aminated. The amination chemoselectivity was examined using substrates featuring multiple activatable C-H bonds. Uniformly, the catalyst showcases high chemoselectivity favoring C-H bonds with lower bond dissociation energy as well as a wide range of functional group tolerance (e.g., ethers, halides, thioetheres, esters, etc.). Sequential cyclization of substrates with ester groups could be achieved, providing facile preparation of an indolizidine framework commonly found in a variety of alkaloids. The amination cyclization reaction mechanism was examined employing nuclear magnetic resonance (NMR) spectroscopy to determine the reaction kinetic profile.
    We discover that analysis in the frozen-hydrated state yields a 10,000 fold increase in signal intensity for polar molecules, such as amino acid, which has important implications for SIMS imaging of metabolites and pharmaceuticals.Optically triggered twisted intramolecular charge transfer (TICT) states in donor-acceptor chromophores form the molecular basis for designing bioimaging probes that sense polarity, microviscosity, and pH in vivo. However, a lack of predictive understanding of the "twist" localization precludes a rational design of TICT-based dyes. Here, using femtosecond stimulated Raman spectroscopy, we reveal a distinct Raman signature of the TICT state for a stilbazolium-class mitochondrial staining dye. Resonance-selective probing of 4-N,N-diethylamino-4″-N'-methyl-stilbazolium tosylate (DEST) tracks the excited-state structure of the dye as it relaxes to a TICT state on a picosecond time scale. The appearance of a remarkably blue-shifted C=C stretching mode at 1650 cm-1 in the TICT state is attributed to the "twist" of a single bond adjacent to the ethylenic π-bridge in the DEST backbone based on detailed electronic structure calculations and vibrational mode analysis. Our work demonstrates that the π-bridge, connecting the donor and acceptor moieties, influences the spatial location of the "twist" and offers a new perspective for designing organelle-specific probes through cogent tuning of backbone dynamics.Enzymes are an important class of biomacromolecules which catalyze many metabolic processes in living systems. Nanomaterials can be synthesized with tailored sizes as well as desired surface modifications, thus acting as promising enzyme regulators. Fluorescent gold nanoclusters (AuNCs) are a representative class of ultrasmall nanoparticles (USNPs) with sizes of ∼2 nm, smaller than most of proteins including enzymes. In this work, we chose α-chymotrypsin (ChT) and AuNCs as the model system. Activity assays and inhibition kinetics studies showed that dihydrolipoic acid (DHLA)-coated AuNCs (DHLA-AuNCs) had a high inhibitory potency (IC50 = 3.4 μM) and high inhibitory efficacy (>80%) on ChT activity through noncompetitive inhibition mechanism. In distinct contrast, glutathione (GSH)-coated AuNCs (GSH-AuNCs) had no significant inhibition effects. Fluorescence spectroscopy, agarose gel electrophoresis and circular dichroism (CD) spectroscopy were conducted to explore the underlying mechanisms. A two-step interaction model was proposed. First, both DHLA-AuNCs and GSH-AuNCs might be bound to the positively charged sites of ChT through electrostatic forces. Second, further hydrophobic interactions occurred between three tyrosine residues of ChT and the hydrophobic carbon chain of DHLA, leading to a significant structural change thus to deactivate ChT on the allosteric site. On the contrary, no such interactions occurred with GSH of zwitterionic characteristic, which explained no inhibitory effect of GSH-AuNCs on ChT. To the best of our knowledge, this is the first example of the allosteric inhibition of ChT by nano regulators. These findings provide a fundamental basis for the design and development of nano regulators.SHP2 (Src homology-2 domain-containing protein tyrosine phosphatase-2) is a non-receptor protein tyrosine phosphatase that removes tyrosine phosphorylation. Functionally, SHP2 serves as an important hub to connect several intracellular oncogenic signaling pathways, such as Jak/STAT, PI3K/AKT, RAS/Raf/MAPK, and PD-1/PD-L1 pathways. https://www.selleckchem.com/products/danicopan.html Mutations and/or overexpression of SHP2 have been associated with genetic developmental diseases and cancers. Because of the role of SHP2 plays in many diseases, the development of inhibitors targeting the catalytic site in SHP2 has been pursued for more than a decade, but none has advanced to clinical development. Recent discovery of allosteric inhibitors has inspired a novel approach to selectively target SHP2 via the non-catalytic site. To date, four SHP2 allosteric inhibitors have entered clinical trials for the treatment of solid tumors. This review will provide a summary of the physiological and biological functions of SHP2 and discuss the development of non-allosteric/allosteric SHP2 inhibitors in recent years.The development of new routes or materials to realize superlubricity under high contact pressure can result in energy-saving and reduction of emissions. In this study, superlubricity (μ = 0.0017) under extreme pressure (717 MPa, more than twice the previously reported liquid superlubricity) between the frictional pair of Si3N4/sapphire was achieved by prerunning-in with a H3PO4 (HP) solution followed by lubrication with an aqueous solution consisting of poly(vinyl alcohol) (PVA) and sodium chloride (NaCl). Under the same test condition, the aqueous PVA lubricant did not show superlubricity. Results of X-ray photoelectron spectroscopy and Raman spectroscopy indicate the formation of a PVA-adsorbed film at the frictional interface after lubrication with PVA but not after lubrication with PVA/NaCl, indicating competitive adsorption between hydrated Na+ ions and PVA molecules. The hydrated Na+ ions adsorbed preferentially to the solid surfaces, causing the transformation of the shear interface from a polymer film/polymer film to a solid/polymer film. Meanwhile, the hydrated Na+ ions also produced hydration repulsion force and induced low shear stress between the solid surfaces. Furthermore, NaCl increased the viscosity of the polymer lubricant, enhanced the hydrodynamic effect between interfaces, and decreased direct contact between the friction pair, causing a further reduction in friction. Thus, the superlubricity of the PVA/NaCl mixture is attributed to the combination of hydration and hydrodynamic effects. This study provides a novel route and mechanism for achieving extreme-pressure superlubricity at the macroscale, through the synergistic lubricating effect of hydrated ions and a polymer solution, propelling the industrial application of superlubricity.A dipyrrin-supported nickel catalyst (AdFL)Ni(py) (AdFL 1,9-di(1-adamantyl)-5-perfluorophenyldipyrrin; py pyridine) displays productive intramolecular C-H bond amination to afford N-heterocyclic products using aliphatic azide substrates. The catalytic amination conditions are mild, requiring 0.1-2 mol% catalyst loading and operational at room temperature. The scope of C-H bond substrates was explored and benzylic, tertiary, secondary, and primary C-H bonds are successfully aminated. The amination chemoselectivity was examined using substrates featuring multiple activatable C-H bonds. Uniformly, the catalyst showcases high chemoselectivity favoring C-H bonds with lower bond dissociation energy as well as a wide range of functional group tolerance (e.g., ethers, halides, thioetheres, esters, etc.). Sequential cyclization of substrates with ester groups could be achieved, providing facile preparation of an indolizidine framework commonly found in a variety of alkaloids. The amination cyclization reaction mechanism was examined employing nuclear magnetic resonance (NMR) spectroscopy to determine the reaction kinetic profile.
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  • Additionally, the chimeric particles were able to bind and deliver antibodies against both intracellular (α-tubulin) and surface-exposed antigens (CD 20). However, the BCP monomer failed to enter mammalian cells. Thus, for the first time, we have demonstrated that the assembled VLPs are essential for internalization. These results demonstrate the potential of the use of chimeric PVBV VLPs in diagnostics and, more importantly, as nanocarriers for intracellular delivery of antibodies.In this study, the complete genomic sequence of a novel virus was determined by next-generation sequencing of a sample from a symptomatic strawberry plant with severe yellow spots and mosaic on its leaves. Its genomic organization and sequence showed that this virus is related to members of the proposed insect-specific genus "Negevirus". The sample also contained sequences from the geranium aphid Acyrthosiphon malvae. Although the virus was detected repeatedly in the same plant during the three following years, no other positive samples were obtained from the surroundings or more-distant locations. Reverse transcription qPCR analysis revealed the presence of both genomic positive and complementary negative strands of the viral genome in the sample, with a 3- to 30-fold excess of the positive strand, indicating active viral replication. As the virus was not detected in any insect species collected at this location, the virus was provisionally named "Fragaria vesca-associated virus 1" (FVaV-1).Each new troponin assay generation is more sensitive, with recent generation high-sensitivity troponin (hsTn) assays able to detect minimal myocardial injury, even in asymptomatic patients. PURPOSE OF THE REVIEW We reviewed recent information on the use of hsTn assays for assessing acute and chronic cardiovascular disease. RECENT FINDINGS hsTn is used for early emergency department diagnosis, accelerating early discharge with a low event rate comparable if not better than current strategies. Low levels of hsTn are detected in a variety of chronic cardiac and non-cardiac conditions, non-disease conditions including heart failure, chemotherapy, and others. These elevations identify a population at increased risk for long-term cardiovascular events. However, management strategies remain unclear. hsTn has substantial advantages in emergency department use. They hold promise for identifying subclinical cardiac disease, with the potential for earlier intervention with the possibility of decreasing disease progression. Additional studies, however, are needed to determine if this strategy will lead to improved outcomes.The 2019 European Congress of Radiology program, "Women in Focus Be Inspired," offered insights from successful women and men for overcoming a number of everyday work and personal life challenges. With regard to balancing career and personal life and achieving well-being, the advice of female and male radiology leaders on the front lines, throughout the world, shares common themes. This paper highlights and expands on points of advice and encouragement from the "Women in Focus" program. The first step is to know yourself, so you can set priorities. Then, take charge, be brave, and follow your dreams, which may not be the same as other people's. Finding balance requires examining your goals and acknowledging that you may not be able to get everything you want all at once. Receiving effective mentorship from numerous sources is key, as is finding an environment that supports your growth. It is important to surround yourself both at work and at home with people who support your ideas and give you a sense of peace, well-being, and resilience. If the culture does not fit, have the courage to move on. Current leaders should reach out to ensure the diversity of future teams. Society benefits, radiology benefits, and our patients benefit from a specialty that values equity, diversity, and inclusiveness.Mounting evidence shows that drug dependence involves the complex interplay between genetics and the environment. Tyrosine hydroxylase (TH) is the rate-limiting enzyme in dopamine (DA) synthesis, which plays an essential role in the development of drug addiction. Noradrenergic dysfunction due to abnormalities TH expression has been implicated in the pathogenesis of drug addiction. https://www.selleckchem.com/products/gcn2-in-1.html We profiled thirteen single-nucleotide polymorphisms (SNPs) and one VNTR (TCAT repeat, UniSTS240,639) in 512 cases and 600 healthy Chinese subjects to evaluate the relationship between common variants within the TH gene and opioids dependence (OD) in the Chinese Han population. The single-marker analysis determined that rs10770141 (p  less then  0.001, OR 1.739, 95% CI 1.302 - 2.323) and rs10770140 (p = 0.002, OR 1.536, 95% CI 1.164 - 2.026) are risk variants for OD. The haplotype-association analyses determined that A-C-C-C was a risk factor (p = 0.006, OR 1.662, 95% CI 1.241 - 2.225) for OD. We also observed a significant association between (TACT)9/9 and the duration of transition from the first time using opioids to the development of opioid dependence (DTFUD) (p = 0.002, OR 2.153, 95% CI 1.319 - 3.513). Taken together, this study suggests that TH gene polymorphisms may contribute to the risk of OD in the Chinese Han population.BACKGROUND Interns are vulnerable to emotional distress and burnout. Little is known about the extent to which interns' well-being can be influenced by peer support provided by their senior residents. OBJECTIVE To elucidate contributors to interns' emotional distress and ways that peer support from senior residents may impact intern well-being. DESIGN Qualitative study using semi-structured interviews conducted December 2017-March 2018. PARTICIPANTS Second year residents (n = 11) in internal medicine at a major academic medical center during the data collection period. APPROACH Constructivist grounded theory approach in which transcripts were analyzed in an iterative fashion using constant comparison to identify themes and to create a conceptual model. KEY RESULTS The investigators identified three themes around emotional distress and two themes around resident peer support. Distress was a pervasive experience among participants, caused by a combination of contextual factors that decreased emotional resilience (e.
    Additionally, the chimeric particles were able to bind and deliver antibodies against both intracellular (α-tubulin) and surface-exposed antigens (CD 20). However, the BCP monomer failed to enter mammalian cells. Thus, for the first time, we have demonstrated that the assembled VLPs are essential for internalization. These results demonstrate the potential of the use of chimeric PVBV VLPs in diagnostics and, more importantly, as nanocarriers for intracellular delivery of antibodies.In this study, the complete genomic sequence of a novel virus was determined by next-generation sequencing of a sample from a symptomatic strawberry plant with severe yellow spots and mosaic on its leaves. Its genomic organization and sequence showed that this virus is related to members of the proposed insect-specific genus "Negevirus". The sample also contained sequences from the geranium aphid Acyrthosiphon malvae. Although the virus was detected repeatedly in the same plant during the three following years, no other positive samples were obtained from the surroundings or more-distant locations. Reverse transcription qPCR analysis revealed the presence of both genomic positive and complementary negative strands of the viral genome in the sample, with a 3- to 30-fold excess of the positive strand, indicating active viral replication. As the virus was not detected in any insect species collected at this location, the virus was provisionally named "Fragaria vesca-associated virus 1" (FVaV-1).Each new troponin assay generation is more sensitive, with recent generation high-sensitivity troponin (hsTn) assays able to detect minimal myocardial injury, even in asymptomatic patients. PURPOSE OF THE REVIEW We reviewed recent information on the use of hsTn assays for assessing acute and chronic cardiovascular disease. RECENT FINDINGS hsTn is used for early emergency department diagnosis, accelerating early discharge with a low event rate comparable if not better than current strategies. Low levels of hsTn are detected in a variety of chronic cardiac and non-cardiac conditions, non-disease conditions including heart failure, chemotherapy, and others. These elevations identify a population at increased risk for long-term cardiovascular events. However, management strategies remain unclear. hsTn has substantial advantages in emergency department use. They hold promise for identifying subclinical cardiac disease, with the potential for earlier intervention with the possibility of decreasing disease progression. Additional studies, however, are needed to determine if this strategy will lead to improved outcomes.The 2019 European Congress of Radiology program, "Women in Focus Be Inspired," offered insights from successful women and men for overcoming a number of everyday work and personal life challenges. With regard to balancing career and personal life and achieving well-being, the advice of female and male radiology leaders on the front lines, throughout the world, shares common themes. This paper highlights and expands on points of advice and encouragement from the "Women in Focus" program. The first step is to know yourself, so you can set priorities. Then, take charge, be brave, and follow your dreams, which may not be the same as other people's. Finding balance requires examining your goals and acknowledging that you may not be able to get everything you want all at once. Receiving effective mentorship from numerous sources is key, as is finding an environment that supports your growth. It is important to surround yourself both at work and at home with people who support your ideas and give you a sense of peace, well-being, and resilience. If the culture does not fit, have the courage to move on. Current leaders should reach out to ensure the diversity of future teams. Society benefits, radiology benefits, and our patients benefit from a specialty that values equity, diversity, and inclusiveness.Mounting evidence shows that drug dependence involves the complex interplay between genetics and the environment. Tyrosine hydroxylase (TH) is the rate-limiting enzyme in dopamine (DA) synthesis, which plays an essential role in the development of drug addiction. Noradrenergic dysfunction due to abnormalities TH expression has been implicated in the pathogenesis of drug addiction. https://www.selleckchem.com/products/gcn2-in-1.html We profiled thirteen single-nucleotide polymorphisms (SNPs) and one VNTR (TCAT repeat, UniSTS240,639) in 512 cases and 600 healthy Chinese subjects to evaluate the relationship between common variants within the TH gene and opioids dependence (OD) in the Chinese Han population. The single-marker analysis determined that rs10770141 (p  less then  0.001, OR 1.739, 95% CI 1.302 - 2.323) and rs10770140 (p = 0.002, OR 1.536, 95% CI 1.164 - 2.026) are risk variants for OD. The haplotype-association analyses determined that A-C-C-C was a risk factor (p = 0.006, OR 1.662, 95% CI 1.241 - 2.225) for OD. We also observed a significant association between (TACT)9/9 and the duration of transition from the first time using opioids to the development of opioid dependence (DTFUD) (p = 0.002, OR 2.153, 95% CI 1.319 - 3.513). Taken together, this study suggests that TH gene polymorphisms may contribute to the risk of OD in the Chinese Han population.BACKGROUND Interns are vulnerable to emotional distress and burnout. Little is known about the extent to which interns' well-being can be influenced by peer support provided by their senior residents. OBJECTIVE To elucidate contributors to interns' emotional distress and ways that peer support from senior residents may impact intern well-being. DESIGN Qualitative study using semi-structured interviews conducted December 2017-March 2018. PARTICIPANTS Second year residents (n = 11) in internal medicine at a major academic medical center during the data collection period. APPROACH Constructivist grounded theory approach in which transcripts were analyzed in an iterative fashion using constant comparison to identify themes and to create a conceptual model. KEY RESULTS The investigators identified three themes around emotional distress and two themes around resident peer support. Distress was a pervasive experience among participants, caused by a combination of contextual factors that decreased emotional resilience (e.
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  • Despite of decreased efficiency, the HRP/ABTS system was able to degrade tetracycline in a domestic wastewater treatment plant effluent matrix, which demonstrates the potential of the system to be utilized in wastewater treatment.The detection of soft deodorized olive oils in extra virgin olive oil (EVOO) has become a challenging task ever since it was demonstrated that 1. The process does not form the typical refining markers, e.g. stigmastadienes, and 2. The determination of the fatty acid alkyl esters renders useful only when the deodorized matrix comes from oils with fermentative defects. Recently researchers have developed strategies to detect such kind of blends, being one of them based on the fact that both diacylglycerol (DAG) and free fatty acids are not interdependent after mild refining activities. Presently, we propose two factors to confirm the absence of soft deodorized oils in EVOO R1 (10 × free acidity/DAGexp) ≥ 0.23 and R2 (DAGexp-DAGtheor) less then 0, in genuine EVOO. We demonstrate that such approach is useful to detect the presence of soft deodorized olive oil when this is at least at 30% in the mixture.The first detailed phytochemical screening was performed on juices prepared from arils of wild pomegranate fruits taken from several locations in Montenegro with the aim of their future valorization. Particular attention is paid to the effect of pomegranate growth conditions on the juice quality. In addition to the basic parameters of pomegranate fruits and juices, nine primary metabolites (sugars, organic acids and vitamin C) were determined in the juices. Among 97 phenolic compounds, 23 anthocyanins and their derivatives, 33 ellagitannins and derivatives of ellagic acid, 12 flavanols, 4 flavonol glycosides, 1 flavone, 17 hydroxybenzoic acids and 7 hydroxycinnamic acids and their derivatives, were identified. Flavanols (1137-4424 mg/L) as well as ellagitannins and ellagic acid derivatives (1849-2991 mg/L) had the highest concentrations in pomegranate juices. Juices from the pomegranates grown on two soil types had total analyzed phenolics ranging from 4387 mg/L (Eutric Cambisol) up to 8461 mg/L (Terra Rossa).The aim of this paper was to evaluate the effect of thermal treatment and UV irradiation on structural and physicochemical properties of octenyl succinate (OS) maize starches differing in content of OS groups (0.76%-2.38%). X-ray diffraction (XRD), gel permeation chromatography (GPC), and electron paramagnetic resonance (EPR) spectroscopy were used to estimate structural characteristics of octenyl succinate starches and their physically treated counterparts. Starch functional properties were also determined. XRD spectra and hydrodynamic volume distribution revealed that growth of octenyl succinate groups' content resulted in stabilization of starch structure, which was confirmed by processes of radical formation, stimulated by thermal and UV treatments. It was found, on the basis of measurements of water binding capacity, water solubility and intrinsic viscosity, that OSA addition changed physicochemical properties of starch and influenced the course of physical modifications. It was established that temperature affected starch properties to a greater extent than UV.The objective of the present study was to investigate the effectiveness of different 1-MCP treatment patterns on alleviating chilling injury (CI) of postharvest nectarine stored at 0 ± 1 °C. Nectarine fruits were subjected to the following treatments Single-High dose 1-MCP treatment (S-H) 1 μL L-1 application before storage; Multi-low dose 1-MCP treatment (M-L) Five 0.25 μL L-1 applications after 0, 5, 10, 15, and 20 d of storage; Multi-high dose 1-MCP treatment (M-H) Five 1 μL L-1 applications after 0, 5, 10, 15 and 20 d of storage. The results showed that although all 1-MCP treatments alleviated CI, M-H 1-MCP treatment is the most effective pattern in alleviating CI of nectarine fruit in S-H, M-L, and M-H 1-MCP treatments. Moreover, this study indicated that the reduction of CI in nectarine by 1-MCP application was related to its regulations of ROS and energy metabolism.The present study aimed to characterize the nutritional value and potential use of elderberries as a source of antioxidant compounds. The chemical composition, fatty acids and phenolic compounds were determined for elderberries. The optimization of extraction parameters was designed with a Box-Behnken design coupled with response surface methodology (RSM) and desirability function analysis. The process parameters tested included extraction temperature, % of ethanol and pH, while response variables were global extraction yield, total phenolic and anthocyanins content (TAC), carotenoids and antioxidant activity. Analyses revealed that elderberry was a rich source of total soluble solids, proteins and polyunsaturated fatty acids (omega-3 38.12 g/100 g and omega-6 39.54 g/100 g fatty acids). Regarding phenolic compounds, elderberries were found abundant in flavonoids (rutin and quercetin), and phenolic acids (i.e. gallic acid and gentisic acid). Finally, numerical optimization indicated that the best extraction parameters were the following temperature 60 °C, 50% of ethanol and pH 2.With the current agro-food industry demands for more environmentally-friendly production, the use of natural antifungal compounds extracted by emerging technologies led to a sustainable alternative to control microorganisms. Therefore, the present work aimed to (i) determine antifungal activity against Colletotrichum gloeosporioides and Penicillium italicum of jackfruit leaf extracts obtained by different methods, and (ii) identify compounds by HPLC-DAD-ESI-MS. Microwave (MAE), high-hydrostatic pressure (HHP) and ultrasound (UAE) assisted extractions were tested, followed by fractionation with different polarity solvents. https://www.selleckchem.com/products/bzatp-triethylammonium-salt.html The concentration of total soluble phenols (TSP), tannins (TT) and flavonoids (TF) were determined. Differences not only in the amounts of extracted phytochemicals were found but in the antifungal properties (MAE against P. italicum and HHP against C. gloeosporioides at 5 mg/ml) as well as in the chemical composition determined by HPLC-MS. These results suggest the possible application of jackfruit leaf extracts as a suitable postharvest antifungal treatment.
    Despite of decreased efficiency, the HRP/ABTS system was able to degrade tetracycline in a domestic wastewater treatment plant effluent matrix, which demonstrates the potential of the system to be utilized in wastewater treatment.The detection of soft deodorized olive oils in extra virgin olive oil (EVOO) has become a challenging task ever since it was demonstrated that 1. The process does not form the typical refining markers, e.g. stigmastadienes, and 2. The determination of the fatty acid alkyl esters renders useful only when the deodorized matrix comes from oils with fermentative defects. Recently researchers have developed strategies to detect such kind of blends, being one of them based on the fact that both diacylglycerol (DAG) and free fatty acids are not interdependent after mild refining activities. Presently, we propose two factors to confirm the absence of soft deodorized oils in EVOO R1 (10 × free acidity/DAGexp) ≥ 0.23 and R2 (DAGexp-DAGtheor) less then 0, in genuine EVOO. We demonstrate that such approach is useful to detect the presence of soft deodorized olive oil when this is at least at 30% in the mixture.The first detailed phytochemical screening was performed on juices prepared from arils of wild pomegranate fruits taken from several locations in Montenegro with the aim of their future valorization. Particular attention is paid to the effect of pomegranate growth conditions on the juice quality. In addition to the basic parameters of pomegranate fruits and juices, nine primary metabolites (sugars, organic acids and vitamin C) were determined in the juices. Among 97 phenolic compounds, 23 anthocyanins and their derivatives, 33 ellagitannins and derivatives of ellagic acid, 12 flavanols, 4 flavonol glycosides, 1 flavone, 17 hydroxybenzoic acids and 7 hydroxycinnamic acids and their derivatives, were identified. Flavanols (1137-4424 mg/L) as well as ellagitannins and ellagic acid derivatives (1849-2991 mg/L) had the highest concentrations in pomegranate juices. Juices from the pomegranates grown on two soil types had total analyzed phenolics ranging from 4387 mg/L (Eutric Cambisol) up to 8461 mg/L (Terra Rossa).The aim of this paper was to evaluate the effect of thermal treatment and UV irradiation on structural and physicochemical properties of octenyl succinate (OS) maize starches differing in content of OS groups (0.76%-2.38%). X-ray diffraction (XRD), gel permeation chromatography (GPC), and electron paramagnetic resonance (EPR) spectroscopy were used to estimate structural characteristics of octenyl succinate starches and their physically treated counterparts. Starch functional properties were also determined. XRD spectra and hydrodynamic volume distribution revealed that growth of octenyl succinate groups' content resulted in stabilization of starch structure, which was confirmed by processes of radical formation, stimulated by thermal and UV treatments. It was found, on the basis of measurements of water binding capacity, water solubility and intrinsic viscosity, that OSA addition changed physicochemical properties of starch and influenced the course of physical modifications. It was established that temperature affected starch properties to a greater extent than UV.The objective of the present study was to investigate the effectiveness of different 1-MCP treatment patterns on alleviating chilling injury (CI) of postharvest nectarine stored at 0 ± 1 °C. Nectarine fruits were subjected to the following treatments Single-High dose 1-MCP treatment (S-H) 1 μL L-1 application before storage; Multi-low dose 1-MCP treatment (M-L) Five 0.25 μL L-1 applications after 0, 5, 10, 15, and 20 d of storage; Multi-high dose 1-MCP treatment (M-H) Five 1 μL L-1 applications after 0, 5, 10, 15 and 20 d of storage. The results showed that although all 1-MCP treatments alleviated CI, M-H 1-MCP treatment is the most effective pattern in alleviating CI of nectarine fruit in S-H, M-L, and M-H 1-MCP treatments. Moreover, this study indicated that the reduction of CI in nectarine by 1-MCP application was related to its regulations of ROS and energy metabolism.The present study aimed to characterize the nutritional value and potential use of elderberries as a source of antioxidant compounds. The chemical composition, fatty acids and phenolic compounds were determined for elderberries. The optimization of extraction parameters was designed with a Box-Behnken design coupled with response surface methodology (RSM) and desirability function analysis. The process parameters tested included extraction temperature, % of ethanol and pH, while response variables were global extraction yield, total phenolic and anthocyanins content (TAC), carotenoids and antioxidant activity. Analyses revealed that elderberry was a rich source of total soluble solids, proteins and polyunsaturated fatty acids (omega-3 38.12 g/100 g and omega-6 39.54 g/100 g fatty acids). Regarding phenolic compounds, elderberries were found abundant in flavonoids (rutin and quercetin), and phenolic acids (i.e. gallic acid and gentisic acid). Finally, numerical optimization indicated that the best extraction parameters were the following temperature 60 °C, 50% of ethanol and pH 2.With the current agro-food industry demands for more environmentally-friendly production, the use of natural antifungal compounds extracted by emerging technologies led to a sustainable alternative to control microorganisms. Therefore, the present work aimed to (i) determine antifungal activity against Colletotrichum gloeosporioides and Penicillium italicum of jackfruit leaf extracts obtained by different methods, and (ii) identify compounds by HPLC-DAD-ESI-MS. Microwave (MAE), high-hydrostatic pressure (HHP) and ultrasound (UAE) assisted extractions were tested, followed by fractionation with different polarity solvents. https://www.selleckchem.com/products/bzatp-triethylammonium-salt.html The concentration of total soluble phenols (TSP), tannins (TT) and flavonoids (TF) were determined. Differences not only in the amounts of extracted phytochemicals were found but in the antifungal properties (MAE against P. italicum and HHP against C. gloeosporioides at 5 mg/ml) as well as in the chemical composition determined by HPLC-MS. These results suggest the possible application of jackfruit leaf extracts as a suitable postharvest antifungal treatment.
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  • In an air-assisted atomizer the parameters of the mechanical atomizer have a **** stronger influence on drop diameters than do characteristics of the air-swirl chamber. Using a mechanical atomizer with optimal geometrical dimensions allows limiting the liquid supply pressure to 5 bar; but when an air-assisted component is introduced we can recommend an ALR ≈ 1 and an air supply pressure of up to 1 bar.A new series of s-triazine hydrazone derivatives was prepared based on the reaction of 6-hydrazino-2,4-disubstituted-s-triazine with p-substituted benzaldehyde derivatives using a straightforward synthetic pathway. The antiproliferative activity of all synthesized compounds was evaluated against two human cancer cell lines; breast cancer MCF-7 and colon carcinoma HCT-116 using MTT assay. Among all, 11 compounds have shown strong to moderate antiproliferative activity with IC50 values in the range 1.01-18.20 µM in MCF-7 and 0.97-19.51 µM in HCT-116. The best results were obtained with 4,4'-(6-(2-(pyridin-2-ylmethylene)hydrazinyl)-1,3,5-triazine-2,4-diyl) dimorpholine 11 (IC50 = 1.0 µM and 0.98 µM in MCF-7 and HCT-116 cell lines, respectively). The substituents on the s-triazine core as well as the substituent at the benzylidene moiety have a great effect on the antiproliferative activity. Whereas compounds containing dimorpholino-s-triazine derivatives 8a-e showed more potent antiproliferative in MCF-7 compared to their analogs 7a-f (compounds containing two-piperidine rings), compounds containing one piperidine and one morpholine ring 9a-f showed better IC50 values in the range 10.4-22.2 µM. On the other hand, compounds containing two-piperidine rings 7a-f showed more potent antiproliferative in HCT-116 (IC50 values in the range 8.8-19.5 µM) than their analogs 8a-e and 9a-f.There is increasing evidence of gastrointestinal (GI) infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We surveyed the co-expression of SARS-CoV-2 entry genes ACE2 and TMPRSS2 throughout the GI tract to assess potential sites of infection. Publicly available and in-house single-cell RNA-sequencing datasets from the GI tract were queried. Enterocytes from the small intestine and colonocytes showed the highest proportions of cells co-expressing ACE2 and TMPRSS2. Therefore, the lower GI tract represents the most likely site of SARS-CoV-2 entry leading to GI infection.Amorphous solid dispersions (ASDs) have been proven to increase the bioavailability of poorly soluble drugs. It is desirable that the ASD provide a rapid dissolution rate and a sufficient stabilization of the generated supersaturation. In many cases, one polymer alone is not able to provide both features, which raises a need for reasonable polymer combinations. In this study we aimed to generate a rapidly dissolving ASD using the hydrophilic polymer polyvinyl alcohol (PVA) combined with a suitable precipitation inhibitor. Initially, PVA and hydroxypropylmethylcellulose acetate succinate (HPMCAS) were screened for their precipitation inhibitory potential for celecoxib in solution. The generated supersaturation in presence of PVA or HPMCAS was further characterized using dynamic light scattering. Binary ASDs of either PVA or HPMCAS (at 10% and 20% drug load) were prepared by hot-melt extrusion and solid-state analytics were conducted using differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD) and fourier-transformed infrared spectroscopy (FT-IR). The non-sink dissolution studies of the binary ASDs revealed a high dissolution rate for the PVA ASDs with subsequent precipitation and for the HPMCAS ASDs a suppressed dissolution. In order to utilize the unexploited potential of the binary ASDs, the PVA ASDs were combined with HPMCAS either predissolved or added as powder and also formulated as ternary ASD. We successfully generated a solid formulation consisting of the powdered PVA ASD and HPMCAS powder, which was superior in monophasic non-sink dissolution and biorelevant biphasic dissolution studies compared to the binary and ternary ASDs.(1) Background Degeneration of the hip abductor mechanism, a well-known cause of functional limitation, is difficult to treat and is associated with a reduced health-related quality of life (HRQOL). The gluteus maximus muscle flap is a treatment option to support a severely degenerative modified gluteus medius muscle. Although several reports exist on the clinical outcome, there remains a gap in the literature regarding HRQOL in conjunction with functional results. (2) Methods The present study consists of 18 patients with a mean age of 64 (53‒79) years, operatively treated with a gluteus maximus flap due to chronic gluteal deficiency. https://www.selleckchem.com/products/ddo-2728.html Fifteen (83%) of these patients presented a history of total hip arthroplasty or revision arthroplasty. Pre and postoperative pain, Trendelenburg sign, internal rotation lag sign, trochanteric pain syndrome, the Harris Hip Score (HHS), and abduction strength after Janda (0‒5) were evaluated. Postoperative patient satisfaction and health-related quality of life, according to theven this condition, the gluteus maximus muscle flap transfer is a viable option for selected patients with chronic gluteal deficiency.Flavonoids are widely used as phytomedicines. Here, we report on flavonoid phytomedicines with potential for development into prophylactics or therapeutics against coronavirus disease 2019 (COVID-19). These flavonoid-based phytomedicines include caflanone, Equivir, hesperetin, myricetin, and Linebacker. Our in silico studies show that these flavonoid-based molecules can bind with high affinity to the spike protein, helicase, and protease sites on the ACE2 receptor used by the severe acute respiratory syndrome coronavirus 2 to infect cells and cause COVID-19. Meanwhile, in vitro studies show potential of caflanone to inhibit virus entry factors including, ABL-2, cathepsin L, cytokines (IL-1β, IL-6, IL-8, Mip-1α, TNF-α), and PI4Kiiiβ as well as AXL-2, which facilitates mother-to-fetus transmission of coronavirus. The potential for the use of smart drug delivery technologies like nanoparticle drones loaded with these phytomedicines to overcome bioavailability limitations and improve therapeutic efficacy are discussed.
    In an air-assisted atomizer the parameters of the mechanical atomizer have a much stronger influence on drop diameters than do characteristics of the air-swirl chamber. Using a mechanical atomizer with optimal geometrical dimensions allows limiting the liquid supply pressure to 5 bar; but when an air-assisted component is introduced we can recommend an ALR ≈ 1 and an air supply pressure of up to 1 bar.A new series of s-triazine hydrazone derivatives was prepared based on the reaction of 6-hydrazino-2,4-disubstituted-s-triazine with p-substituted benzaldehyde derivatives using a straightforward synthetic pathway. The antiproliferative activity of all synthesized compounds was evaluated against two human cancer cell lines; breast cancer MCF-7 and colon carcinoma HCT-116 using MTT assay. Among all, 11 compounds have shown strong to moderate antiproliferative activity with IC50 values in the range 1.01-18.20 µM in MCF-7 and 0.97-19.51 µM in HCT-116. The best results were obtained with 4,4'-(6-(2-(pyridin-2-ylmethylene)hydrazinyl)-1,3,5-triazine-2,4-diyl) dimorpholine 11 (IC50 = 1.0 µM and 0.98 µM in MCF-7 and HCT-116 cell lines, respectively). The substituents on the s-triazine core as well as the substituent at the benzylidene moiety have a great effect on the antiproliferative activity. Whereas compounds containing dimorpholino-s-triazine derivatives 8a-e showed more potent antiproliferative in MCF-7 compared to their analogs 7a-f (compounds containing two-piperidine rings), compounds containing one piperidine and one morpholine ring 9a-f showed better IC50 values in the range 10.4-22.2 µM. On the other hand, compounds containing two-piperidine rings 7a-f showed more potent antiproliferative in HCT-116 (IC50 values in the range 8.8-19.5 µM) than their analogs 8a-e and 9a-f.There is increasing evidence of gastrointestinal (GI) infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We surveyed the co-expression of SARS-CoV-2 entry genes ACE2 and TMPRSS2 throughout the GI tract to assess potential sites of infection. Publicly available and in-house single-cell RNA-sequencing datasets from the GI tract were queried. Enterocytes from the small intestine and colonocytes showed the highest proportions of cells co-expressing ACE2 and TMPRSS2. Therefore, the lower GI tract represents the most likely site of SARS-CoV-2 entry leading to GI infection.Amorphous solid dispersions (ASDs) have been proven to increase the bioavailability of poorly soluble drugs. It is desirable that the ASD provide a rapid dissolution rate and a sufficient stabilization of the generated supersaturation. In many cases, one polymer alone is not able to provide both features, which raises a need for reasonable polymer combinations. In this study we aimed to generate a rapidly dissolving ASD using the hydrophilic polymer polyvinyl alcohol (PVA) combined with a suitable precipitation inhibitor. Initially, PVA and hydroxypropylmethylcellulose acetate succinate (HPMCAS) were screened for their precipitation inhibitory potential for celecoxib in solution. The generated supersaturation in presence of PVA or HPMCAS was further characterized using dynamic light scattering. Binary ASDs of either PVA or HPMCAS (at 10% and 20% drug load) were prepared by hot-melt extrusion and solid-state analytics were conducted using differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD) and fourier-transformed infrared spectroscopy (FT-IR). The non-sink dissolution studies of the binary ASDs revealed a high dissolution rate for the PVA ASDs with subsequent precipitation and for the HPMCAS ASDs a suppressed dissolution. In order to utilize the unexploited potential of the binary ASDs, the PVA ASDs were combined with HPMCAS either predissolved or added as powder and also formulated as ternary ASD. We successfully generated a solid formulation consisting of the powdered PVA ASD and HPMCAS powder, which was superior in monophasic non-sink dissolution and biorelevant biphasic dissolution studies compared to the binary and ternary ASDs.(1) Background Degeneration of the hip abductor mechanism, a well-known cause of functional limitation, is difficult to treat and is associated with a reduced health-related quality of life (HRQOL). The gluteus maximus muscle flap is a treatment option to support a severely degenerative modified gluteus medius muscle. Although several reports exist on the clinical outcome, there remains a gap in the literature regarding HRQOL in conjunction with functional results. (2) Methods The present study consists of 18 patients with a mean age of 64 (53‒79) years, operatively treated with a gluteus maximus flap due to chronic gluteal deficiency. https://www.selleckchem.com/products/ddo-2728.html Fifteen (83%) of these patients presented a history of total hip arthroplasty or revision arthroplasty. Pre and postoperative pain, Trendelenburg sign, internal rotation lag sign, trochanteric pain syndrome, the Harris Hip Score (HHS), and abduction strength after Janda (0‒5) were evaluated. Postoperative patient satisfaction and health-related quality of life, according to theven this condition, the gluteus maximus muscle flap transfer is a viable option for selected patients with chronic gluteal deficiency.Flavonoids are widely used as phytomedicines. Here, we report on flavonoid phytomedicines with potential for development into prophylactics or therapeutics against coronavirus disease 2019 (COVID-19). These flavonoid-based phytomedicines include caflanone, Equivir, hesperetin, myricetin, and Linebacker. Our in silico studies show that these flavonoid-based molecules can bind with high affinity to the spike protein, helicase, and protease sites on the ACE2 receptor used by the severe acute respiratory syndrome coronavirus 2 to infect cells and cause COVID-19. Meanwhile, in vitro studies show potential of caflanone to inhibit virus entry factors including, ABL-2, cathepsin L, cytokines (IL-1β, IL-6, IL-8, Mip-1α, TNF-α), and PI4Kiiiβ as well as AXL-2, which facilitates mother-to-fetus transmission of coronavirus. The potential for the use of smart drug delivery technologies like nanoparticle drones loaded with these phytomedicines to overcome bioavailability limitations and improve therapeutic efficacy are discussed.
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  • Many infectious diseases are still prevalent in the world's populations since no effective treatments are available to eradicate them. The reasons may either be the antibiotic resistance towards the available therapeutic molecules or the slow rate of producing adequate therapeutic regimens to tackle the rapid growth of new infectious diseases, as well as the toxicity of current treatment regimens. Due to these reasons, there is a need to seek and develop novel therapeutic regimens to reduce the rapid scale of bacterial infections. Antimicrobial Peptides (AMPs) are components of the first line of defense for prokaryotes and eukaryotes and have a wide range of activities against Gram-negative and Gram-positive bacteria, fungi, cancer cells, and protozoa, as well as viruses. In this study, peptides which were initially identified for their HIV inhibitory activity were further screened for antibacterial activity through determination of their kinetics as well as their cytotoxicity. From the results obtained, the **** of two AMPs (Molecule 3 and Molecule 7) were 12.5 μg/ml for K. pneumoniae (ATCC 700603) and 6.25 μg/ml for P. aeruginosa (ATCC 22108). The two AMPs killed these bacteria rapidly in vitro, preventing bacterial growth within few hours of treatment. Furthermore, the cytotoxic activity of these two peptides was significantly low, even at an AMP concentration of 100 μg/ml. These results revealed that Molecule 3 and 7 have great potential as antibacterial drugs or could serve as lead compounds in the design of therapeutic regimens for the treatment of antibiotic-resistant bacteria. Copyright © 2020 Marius B. Tincho et al.The existing dental curriculum is taught at the College of Dentistry since 2002. The aim of this research is to explore the satisfaction levels of faculty members and students with that curriculum. This information will justify a curriculum reformation plan that addresses the aspirations of both faculty members and students. In this cross-sectional study, a two-section survey was prepared. Section 1 investigated the level of satisfaction with the curriculum, and Section 2 sought reasons why participants were satisfied with the curriculum. The questionnaire was electronically mailed to faculty members, interns, and senior students. Data were analyzed to identify patterns and points of disagreement expressed by faculty and students. The overall response rate was 68.7%. https://www.selleckchem.com/products/TG100-115.html The mean standard deviation (SD) score in the study sample from all respondents was 5.0 (+3.0). Faculty significantly registered higher satisfaction than students (mean (SD) = 5.9 (+2.9) and 4.1 (+2.8), P = 0.002). Results of multivariate analysis showed that faculty members were more satisfied with the curriculum than students because they thought the curriculum prepared competent graduates (regression coefficient = 1.76 and 0.69). Teaching staff and students' satisfaction levels with the curriculum were significantly associated with their perception that the curriculum produces competent graduates. Areas with low students' satisfaction levels were related to promotion of engagement with others and development of critical thinking and problem-solving skills. These areas should be the focus of future curriculum reformation to prepare competitive graduates with competences aligned with the recommendations of the Saudi Arabia Qualification Framework and of the international benchmarks. Copyright © 2020 Maha Abdelsalam et al.Aim To evaluate dentinal microcrack formation on root canals instrumented, continuously in the body temperature, with XP-endo shaper (XPES) and ProTaper Universal (PTU), by means of microcomputed tomographic (micro-CT) analysis. Methodology. Nineteen mesial roots with two separate canals (Vertucci Type IV) of extracted mandibular molars were used in this study. The root canals (N = 38) were divided into 2 groups. Group 1 (n = 19) all MB canals were instrumented with XPES. Group 2 (n = 19) all ML canals were instrumented with PTU. All roots were scanned with micro-CT before and after instrumentation. Two precalibrated examiners evaluated the cross-sectional images of each sample with DataViewer program. The dentinal microcracks (complete and incomplete) were counted in each third of the root for the preinstrumentation and the postinstrumentation images. Wilcoxin signed-rank and Mann-Whitney U tests were used for statistical analysis at a significance level of P less then 0.05. Results The number of microcracks increased significantly (P less then 0.05) after instrumentation with XPES in the middle and cervical thirds. The number of microcracks increased significantly (P less then 0.05) after instrumentation with PTU in the cervical third only. There was no significant difference between the groups in the cervical and apical thirds. In the middle third, the XPES induced more incomplete microcracks than PTU (P less then 0.05). Conclusion Within the limitations of this study, there was no significant difference in the dentinal microcrack formation between XPES and PTU in the apical and cervical thirds of the root. However, XPES instrumentation induced more incomplete microcracks than PTU in the middle third of human roots. Copyright © 2020 Sarah M. Alkahtany and Ebtissam M. Al-Madi.Germline BRCA1 and BRCA2 mutations confer an increased lifetime risk for breast cancer and ovarian cancer. Several studies have investigated prognosis among BRCA1/2 mutation carriers and noncarriers, but the prognostic impact on outcomes of breast cancer patients has not been determined. The aim of this study was to determine the prognosis of TNBC patients with and without BRCA1/2 germline mutation. Among 502 patients diagnosed with TNBC between 2005 and 2008, 124 patients with a strong family history of breast cancer or ovarian cancer as well as TNBC patients diagnosed under 45 years were referred to the Genetic Counseling Unit for genetic counselling and genetic tests. In 30 (24%) of them, the BRCA1/2 mutation was detected (the most common 5382insC in 18 (60%) patients). The median follow-up of the entire group was 60 months. BRCA1/2 mutation carriers were statistically significantly younger at TNBC diagnosis compared with nonmutation patients (41 vs 47 years, respectively). Patients with the BRCA1/2 mutation had smaller tumors (stage I 47% vs 24.
    Many infectious diseases are still prevalent in the world's populations since no effective treatments are available to eradicate them. The reasons may either be the antibiotic resistance towards the available therapeutic molecules or the slow rate of producing adequate therapeutic regimens to tackle the rapid growth of new infectious diseases, as well as the toxicity of current treatment regimens. Due to these reasons, there is a need to seek and develop novel therapeutic regimens to reduce the rapid scale of bacterial infections. Antimicrobial Peptides (AMPs) are components of the first line of defense for prokaryotes and eukaryotes and have a wide range of activities against Gram-negative and Gram-positive bacteria, fungi, cancer cells, and protozoa, as well as viruses. In this study, peptides which were initially identified for their HIV inhibitory activity were further screened for antibacterial activity through determination of their kinetics as well as their cytotoxicity. From the results obtained, the MICs of two AMPs (Molecule 3 and Molecule 7) were 12.5 μg/ml for K. pneumoniae (ATCC 700603) and 6.25 μg/ml for P. aeruginosa (ATCC 22108). The two AMPs killed these bacteria rapidly in vitro, preventing bacterial growth within few hours of treatment. Furthermore, the cytotoxic activity of these two peptides was significantly low, even at an AMP concentration of 100 μg/ml. These results revealed that Molecule 3 and 7 have great potential as antibacterial drugs or could serve as lead compounds in the design of therapeutic regimens for the treatment of antibiotic-resistant bacteria. Copyright © 2020 Marius B. Tincho et al.The existing dental curriculum is taught at the College of Dentistry since 2002. The aim of this research is to explore the satisfaction levels of faculty members and students with that curriculum. This information will justify a curriculum reformation plan that addresses the aspirations of both faculty members and students. In this cross-sectional study, a two-section survey was prepared. Section 1 investigated the level of satisfaction with the curriculum, and Section 2 sought reasons why participants were satisfied with the curriculum. The questionnaire was electronically mailed to faculty members, interns, and senior students. Data were analyzed to identify patterns and points of disagreement expressed by faculty and students. The overall response rate was 68.7%. https://www.selleckchem.com/products/TG100-115.html The mean standard deviation (SD) score in the study sample from all respondents was 5.0 (+3.0). Faculty significantly registered higher satisfaction than students (mean (SD) = 5.9 (+2.9) and 4.1 (+2.8), P = 0.002). Results of multivariate analysis showed that faculty members were more satisfied with the curriculum than students because they thought the curriculum prepared competent graduates (regression coefficient = 1.76 and 0.69). Teaching staff and students' satisfaction levels with the curriculum were significantly associated with their perception that the curriculum produces competent graduates. Areas with low students' satisfaction levels were related to promotion of engagement with others and development of critical thinking and problem-solving skills. These areas should be the focus of future curriculum reformation to prepare competitive graduates with competences aligned with the recommendations of the Saudi Arabia Qualification Framework and of the international benchmarks. Copyright © 2020 Maha Abdelsalam et al.Aim To evaluate dentinal microcrack formation on root canals instrumented, continuously in the body temperature, with XP-endo shaper (XPES) and ProTaper Universal (PTU), by means of microcomputed tomographic (micro-CT) analysis. Methodology. Nineteen mesial roots with two separate canals (Vertucci Type IV) of extracted mandibular molars were used in this study. The root canals (N = 38) were divided into 2 groups. Group 1 (n = 19) all MB canals were instrumented with XPES. Group 2 (n = 19) all ML canals were instrumented with PTU. All roots were scanned with micro-CT before and after instrumentation. Two precalibrated examiners evaluated the cross-sectional images of each sample with DataViewer program. The dentinal microcracks (complete and incomplete) were counted in each third of the root for the preinstrumentation and the postinstrumentation images. Wilcoxin signed-rank and Mann-Whitney U tests were used for statistical analysis at a significance level of P less then 0.05. Results The number of microcracks increased significantly (P less then 0.05) after instrumentation with XPES in the middle and cervical thirds. The number of microcracks increased significantly (P less then 0.05) after instrumentation with PTU in the cervical third only. There was no significant difference between the groups in the cervical and apical thirds. In the middle third, the XPES induced more incomplete microcracks than PTU (P less then 0.05). Conclusion Within the limitations of this study, there was no significant difference in the dentinal microcrack formation between XPES and PTU in the apical and cervical thirds of the root. However, XPES instrumentation induced more incomplete microcracks than PTU in the middle third of human roots. Copyright © 2020 Sarah M. Alkahtany and Ebtissam M. Al-Madi.Germline BRCA1 and BRCA2 mutations confer an increased lifetime risk for breast cancer and ovarian cancer. Several studies have investigated prognosis among BRCA1/2 mutation carriers and noncarriers, but the prognostic impact on outcomes of breast cancer patients has not been determined. The aim of this study was to determine the prognosis of TNBC patients with and without BRCA1/2 germline mutation. Among 502 patients diagnosed with TNBC between 2005 and 2008, 124 patients with a strong family history of breast cancer or ovarian cancer as well as TNBC patients diagnosed under 45 years were referred to the Genetic Counseling Unit for genetic counselling and genetic tests. In 30 (24%) of them, the BRCA1/2 mutation was detected (the most common 5382insC in 18 (60%) patients). The median follow-up of the entire group was 60 months. BRCA1/2 mutation carriers were statistically significantly younger at TNBC diagnosis compared with nonmutation patients (41 vs 47 years, respectively). Patients with the BRCA1/2 mutation had smaller tumors (stage I 47% vs 24.
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  • We continue our review of issues related to measurement error and misclassification in epidemiology. We further describe methods of adjusting for biased estimation caused by measurement error in continuous covariates, covering likelihood methods, Bayesian methods, moment reconstruction, moment-adjusted imputation, and multiple imputation. We then describe which methods can also be used with misclassification of categorical covariates. Methods of adjusting estimation of distributions of continuous variables for measurement error are then reviewed. Illustrative examples are provided throughout these sections. We provide lists of available software for implementing these methods and also provide the code for implementing our examples in the Supporting Information. Next, we present several advanced topics, including data subject to both classical and Berkson error, modeling continuous exposures with measurement error, and categorical exposures with misclassification in the same model, variable selection when some of the variables are measured with error, adjusting analyses or design for error in an outcome variable, and categorizing continuous variables measured with error. Finally, we provide some advice for the often met situations where variables are known to be measured with substantial error, but there is only an external reference standard or partial (or no) information about the type or magnitude of the error. https://www.selleckchem.com/products/MK-1775.html Published 2020. This article is a U.S. Government work and is in the public domain in the USA.OBJECTIVES The prevalence of Alzheimer's disease and associated disorders is increasing. Rural residents in the United States have less access to memory care specialists and educational and community resources than in other areas of the country. Over a decade ago, we initiated an interdisciplinary rural caregiving telemedicine program to reach Kentucky residents in areas of the state where resources for supporting individuals with dementia are limited. Telemedicine programs involve a short informational presentation followed by a question and answer session; programs are offered 4 times a year. The purpose of this study was to explore questions asked over 1 year of the rural caregiving telemedicine program-encompassing 5 programs-to identify the scope of dementia-related knowledge gaps among attendees. METHODS Questions from the 5 programs were recorded and content analyzed to identify areas of frequent informational requests. RESULTS There were a total of 69 questions over the 5 sessions. For each program, questions ended due to time constraints rather than exhausting all inquiries. The most common topical areas of questions related to risk factors, behavioral management, diagnosis, and medications. DISCUSSION AND IMPLICATIONS This study highlights that rural caregivers in Kentucky have diverse dementia educational needs. Rural communities may benefit from additional, targeted resources addressing these common areas of unmet informational needs. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.Currently, type 1 diabetes requires lifelong insulin injection and careful blood glucose control to prevent secondary complications, but, islet transplantation could make type 1 diabetic patient insulin independent. On the other hand, islet transplantation needs human donors and donor shortage is the most serious issue. To alleviate the donor shortage, non-heart beating and living donor were used, in addition, the efficacy of islet isolation and transplantation has been improved. However, the donor shortage issue will not be solved as long as human donor is the only source. To solve the donor shortage issue, islet xenotransplantation using porcine islets was initiated in 1994. Islet xenotransplantation has a potential to cure many type 1 diabetic patients, on the other hand, there is the risk of developing serious or novel infection. Therefore, WHO has been interested in the xenotransplantation, and international xenotransplantation association (IXA) has published the consensus statements to initiate xenogeneic islet transplantation. Clinical islet xenotransplantation was conducted under the official regulation, and safety and efficacy data have been accumulated. Currently efficient method to overcome xeno-rejection is an important research target. In addition to traditional immunosuppressive drugs, and immune isolation methods, the gene modification with CRISPR and blastocyst complementation have been investigated with promising outcomes. Once, xeno-rejection issue is overcome, islet xenotransplantation should become a curative treatment for type 1 diabetic patients. This article is protected by copyright. All rights reserved.Two new abietane diterpenoids , (3 S , 5 R , 10 S )-3-hydroxy-12-O-demethyl-11-deoxy-19 (4→3)- abeo -cryptojaponol ( 1 ), (4 S , 5 R , 10 S )-12,19-dihydroxy-7-oxoabieta-8,11,13-triene ( 2 ), were isolated from Selaginella moellendorffii Hieron , together with one known abietane diterpenoid ( 3) and four known tetracyclic triterpenoids ( 4-7 ) . Their structures were characterized by their 1D- and 2D-NMR, ECD and mass spectral studies . All compounds were tested for their inhibitory effects on proliferation of three human cancer cells (human non-small-cell lung carcinoma cell line A549 and human breast adenocarcinoma cell lines MDA-MB-231 and MCF-7) in vitro . Among them, compounds 2 , 4 , and 6 displayed modest cytotoxic activities against the above three human cancer cell lines with IC 50 values ranging from 16.28 to 40.67 μM. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.How do speakers learn the social meaning of different linguistic variants, and what factors influence how likely a particular social-linguistic association is to be learned? It has been argued that the social meaning of more salient variants should be learned faster, and that learners' pre-existing experience of a variant will influence its salience. In this paper, we report two artificial-language-learning experiments investigating this. Each experiment involved two language-learning stages followed by a test. The first stage introduced the artificial language and trained participants in it, while the second stage added a simple social context using images of cartoon aliens. The first learning stage was intended to establish participants' experience with the artificial language in general and with the distribution of linguistic variants in particular. The second stage, in which linguistic stimuli were accompanied by images of particular aliens, was intended to simulate the acquisition of linguistic variants in a social context.
    We continue our review of issues related to measurement error and misclassification in epidemiology. We further describe methods of adjusting for biased estimation caused by measurement error in continuous covariates, covering likelihood methods, Bayesian methods, moment reconstruction, moment-adjusted imputation, and multiple imputation. We then describe which methods can also be used with misclassification of categorical covariates. Methods of adjusting estimation of distributions of continuous variables for measurement error are then reviewed. Illustrative examples are provided throughout these sections. We provide lists of available software for implementing these methods and also provide the code for implementing our examples in the Supporting Information. Next, we present several advanced topics, including data subject to both classical and Berkson error, modeling continuous exposures with measurement error, and categorical exposures with misclassification in the same model, variable selection when some of the variables are measured with error, adjusting analyses or design for error in an outcome variable, and categorizing continuous variables measured with error. Finally, we provide some advice for the often met situations where variables are known to be measured with substantial error, but there is only an external reference standard or partial (or no) information about the type or magnitude of the error. https://www.selleckchem.com/products/MK-1775.html Published 2020. This article is a U.S. Government work and is in the public domain in the USA.OBJECTIVES The prevalence of Alzheimer's disease and associated disorders is increasing. Rural residents in the United States have less access to memory care specialists and educational and community resources than in other areas of the country. Over a decade ago, we initiated an interdisciplinary rural caregiving telemedicine program to reach Kentucky residents in areas of the state where resources for supporting individuals with dementia are limited. Telemedicine programs involve a short informational presentation followed by a question and answer session; programs are offered 4 times a year. The purpose of this study was to explore questions asked over 1 year of the rural caregiving telemedicine program-encompassing 5 programs-to identify the scope of dementia-related knowledge gaps among attendees. METHODS Questions from the 5 programs were recorded and content analyzed to identify areas of frequent informational requests. RESULTS There were a total of 69 questions over the 5 sessions. For each program, questions ended due to time constraints rather than exhausting all inquiries. The most common topical areas of questions related to risk factors, behavioral management, diagnosis, and medications. DISCUSSION AND IMPLICATIONS This study highlights that rural caregivers in Kentucky have diverse dementia educational needs. Rural communities may benefit from additional, targeted resources addressing these common areas of unmet informational needs. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.Currently, type 1 diabetes requires lifelong insulin injection and careful blood glucose control to prevent secondary complications, but, islet transplantation could make type 1 diabetic patient insulin independent. On the other hand, islet transplantation needs human donors and donor shortage is the most serious issue. To alleviate the donor shortage, non-heart beating and living donor were used, in addition, the efficacy of islet isolation and transplantation has been improved. However, the donor shortage issue will not be solved as long as human donor is the only source. To solve the donor shortage issue, islet xenotransplantation using porcine islets was initiated in 1994. Islet xenotransplantation has a potential to cure many type 1 diabetic patients, on the other hand, there is the risk of developing serious or novel infection. Therefore, WHO has been interested in the xenotransplantation, and international xenotransplantation association (IXA) has published the consensus statements to initiate xenogeneic islet transplantation. Clinical islet xenotransplantation was conducted under the official regulation, and safety and efficacy data have been accumulated. Currently efficient method to overcome xeno-rejection is an important research target. In addition to traditional immunosuppressive drugs, and immune isolation methods, the gene modification with CRISPR and blastocyst complementation have been investigated with promising outcomes. Once, xeno-rejection issue is overcome, islet xenotransplantation should become a curative treatment for type 1 diabetic patients. This article is protected by copyright. All rights reserved.Two new abietane diterpenoids , (3 S , 5 R , 10 S )-3-hydroxy-12-O-demethyl-11-deoxy-19 (4→3)- abeo -cryptojaponol ( 1 ), (4 S , 5 R , 10 S )-12,19-dihydroxy-7-oxoabieta-8,11,13-triene ( 2 ), were isolated from Selaginella moellendorffii Hieron , together with one known abietane diterpenoid ( 3) and four known tetracyclic triterpenoids ( 4-7 ) . Their structures were characterized by their 1D- and 2D-NMR, ECD and mass spectral studies . All compounds were tested for their inhibitory effects on proliferation of three human cancer cells (human non-small-cell lung carcinoma cell line A549 and human breast adenocarcinoma cell lines MDA-MB-231 and MCF-7) in vitro . Among them, compounds 2 , 4 , and 6 displayed modest cytotoxic activities against the above three human cancer cell lines with IC 50 values ranging from 16.28 to 40.67 μM. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.How do speakers learn the social meaning of different linguistic variants, and what factors influence how likely a particular social-linguistic association is to be learned? It has been argued that the social meaning of more salient variants should be learned faster, and that learners' pre-existing experience of a variant will influence its salience. In this paper, we report two artificial-language-learning experiments investigating this. Each experiment involved two language-learning stages followed by a test. The first stage introduced the artificial language and trained participants in it, while the second stage added a simple social context using images of cartoon aliens. The first learning stage was intended to establish participants' experience with the artificial language in general and with the distribution of linguistic variants in particular. The second stage, in which linguistic stimuli were accompanied by images of particular aliens, was intended to simulate the acquisition of linguistic variants in a social context.
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  • in English, German ZIEL  Testen der Benutzerfreundlichkeit (Usability) und des Anwendungserlebnisses eines neu entwickelten eLearning-Tools zum Unterrichten von Medizinstudenten in PET/CT und CT. METHODEN  Das eLearning-Tool ermöglicht die webbasierte Darstellung von PET- und CT-DICOM-Bildern. Es enthält Bilder eines Normalprobanden mit Annotationen der anatomischen Strukturen und eine klinische Fallstudie. https://www.selleckchem.com/products/Staurosporine.html Die Usability und das Anwendungserlebnis des eLearning-Tools wurde an Medizinstudenten der Medizinischen Fakultät der RWTH Aachen evaluiert. Wir haben eine Umfrage durchgeführt, die auf verschiedenen bereits existierenden und validierten Fragebögen wie System-Usability-Scale (SUS) und User-Experience-Questionnaire (UEQ-S) sowie auf spezifischen Fragen zum eLearning-Tool basiert. ERGEBNISSE  38 Freiwillige (9 Männer) nahmen an unserer Studie teil. Die Anwendung des SUS ergab einen Mittelwert von 82,24 und einen Median von 83,75. Diese positive Bewertung wird durch die Ergebnisse der UEQ-S gestützt, die hinsichtlich der pragmatischen Qualität 2,2, hinsichtlich der hedonistischen Qualität 2,3 und hinsichtlich der Gesamtqualität 2,3 betrugen, was auf eine sehr positive Bewertung hindeutet. In den Freitextantworten wurde der einfache und intuitive Umgang mit dem zusätzlich als interessant und spannend bezeichneten eLearning-Tool hervorgehoben. Die Studierenden äußerten sich auch positiv über die Fallstudie und die Möglichkeit des praxisbezogenen Lernens. Negative Aspekte waren hauptsächlich Probleme bei der Synchronisation der PET- und CT-Bilder. SCHLUSSFOLGERUNGEN  Die positive Bewertung ist ermutigend und bildet eine Grundlage für die Weiterentwicklung des eLearning-Moduls. Es kann die Grundlage für die Umsetzung eines nachhaltigen Blended-Learning-Konzepts im nuklearmedizinischen Lehrplan sein.in English, German HINTERGRUND Das Praktische Jahr (PJ) stellt als letzter Abschnitt des Medizinstudiums eine prägende Ausbildungszeit dar, in der medizinisches Wissen konsequent in ärztliche Kompetenzen umgewandelt werden soll. Seit Novellierung der Ärztlichen Approbationsordnung (ÄApprO) vom 17. Juli 2012 sind ab 1. April 2013 die deutschen Universitäten verpflichtet, einen Ausbildungsplan in Form von PJ-Logbüchern für das Praktische Jahr in den Pflichttertialen Chirurgie und Innere Medizin bereitzustellen. In Vorbereitung dieser Neuerung hat der Medizinische Fakultätentag (MFT) im Juni 2012 Basis-Logbücher als Konsensusdokumente vorgelegt. An der Medizinischen Fakultät der Universität Magdeburg wird zur Ausbildung der PJ-Studierenden im Fach Chirurgie ein klinikspezifisches und in Eigeninitiative entwickeltes Portfolio genutzt. Es wurde überarbeitet und zu einem konkretisierten, alltagsbezogenen und stark klinisch orientierten, fakultätsspezifischen PJ-Logbuch nach Vorgabe des MFT umgestaltet. Ziel dieses des MFT und ist gleichzeitig an die Gegebenheiten und die Lehre der Magdeburger Medizinischen Fakultät angepasst. Den Studierenden wird ein alltagsbezogenes, klinisch relevantes Dokument an die Hand gegeben, um gemeinsam mit einem schlüssigen Ausbildungskonzept unverzichtbare praktisch-klinische Kompetenzen zu erwerben.BACKGROUND UW Medicine was one of the first health systems to encounter and treat COVID-19 patients in the United States, starting in late February 2020. OBJECTIVE Here we describe the rapid rollout of capabilities by UW Medicine Information Technology Services (ITS) to support our clinical response to the COVID-19 pandemic and provide recommendations for health systems to urgently consider, as they plan their own response to this and potentially other future pandemics. METHODS Our recommendations include establishing a hospital incident command structure that includes tight integration with IT, creating automated dashboards for incident command, optimizing emergency communication to staff and patients, and preparing human resources, security, other policies, and equipment to support the transition of all nonessential staff to telework.We describe how UW Medicine quickly expanded telemedicine capabilities to include most primary care providers and increasing numbers of specialty providers. We look at how we managed expedited change control processes to quickly update electronic health records (EHR) with new COVID-19 laboratory and clinical workflows. We also examine the integration of new technology such as tele-intensive care (ICU) equipment and improved integration with teleconferencing software into our EHR. To support the rapid preparation for COVID-19 at other health systems, we include samples of the UW Medicine's COVID-19 order set, COVID-19 documentation template, dashboard metric categories, and a list of the top 10 things your health care IT organization can do now to prepare. CONCLUSION The COVID-19 response requires new and expedited ways of approaching ITS support to clinical needs. UW Medicine ITS leadership hope that by quickly sharing our nimble response to clinical and operational requests, we can help other systems prepare to respond to this public health emergency. Georg Thieme Verlag KG Stuttgart · New York.BACKGROUND  With the consequences of inadequate dosing ranging from increased bleeding risk to excessive drug costs and undesirable administration regimens, the antihemophilic factors are uniquely suited to dose individualization. However, existing options for individualization are limited and exist outside the flow of care. We developed clinical decision support (CDS) software that is integrated with our electronic health record (EHR) and designed to streamline the process for our hematology providers. OBJECTIVES  The aim of this study is to develop and examine the usability of a CDS tool for antihemophilic factor dose individualization. METHODS  Our development strategy was based on the features associated with successful CDS tools and driven by a formal requirements analysis. The ****-end code was based on algorithms developed for manual individualization and unit tested with 23,000 simulated patient profiles created from the range of patient-derived pharmacokinetic parameter estimates defined in children and adults.
    in English, German ZIEL  Testen der Benutzerfreundlichkeit (Usability) und des Anwendungserlebnisses eines neu entwickelten eLearning-Tools zum Unterrichten von Medizinstudenten in PET/CT und CT. METHODEN  Das eLearning-Tool ermöglicht die webbasierte Darstellung von PET- und CT-DICOM-Bildern. Es enthält Bilder eines Normalprobanden mit Annotationen der anatomischen Strukturen und eine klinische Fallstudie. https://www.selleckchem.com/products/Staurosporine.html Die Usability und das Anwendungserlebnis des eLearning-Tools wurde an Medizinstudenten der Medizinischen Fakultät der RWTH Aachen evaluiert. Wir haben eine Umfrage durchgeführt, die auf verschiedenen bereits existierenden und validierten Fragebögen wie System-Usability-Scale (SUS) und User-Experience-Questionnaire (UEQ-S) sowie auf spezifischen Fragen zum eLearning-Tool basiert. ERGEBNISSE  38 Freiwillige (9 Männer) nahmen an unserer Studie teil. Die Anwendung des SUS ergab einen Mittelwert von 82,24 und einen Median von 83,75. Diese positive Bewertung wird durch die Ergebnisse der UEQ-S gestützt, die hinsichtlich der pragmatischen Qualität 2,2, hinsichtlich der hedonistischen Qualität 2,3 und hinsichtlich der Gesamtqualität 2,3 betrugen, was auf eine sehr positive Bewertung hindeutet. In den Freitextantworten wurde der einfache und intuitive Umgang mit dem zusätzlich als interessant und spannend bezeichneten eLearning-Tool hervorgehoben. Die Studierenden äußerten sich auch positiv über die Fallstudie und die Möglichkeit des praxisbezogenen Lernens. Negative Aspekte waren hauptsächlich Probleme bei der Synchronisation der PET- und CT-Bilder. SCHLUSSFOLGERUNGEN  Die positive Bewertung ist ermutigend und bildet eine Grundlage für die Weiterentwicklung des eLearning-Moduls. Es kann die Grundlage für die Umsetzung eines nachhaltigen Blended-Learning-Konzepts im nuklearmedizinischen Lehrplan sein.in English, German HINTERGRUND Das Praktische Jahr (PJ) stellt als letzter Abschnitt des Medizinstudiums eine prägende Ausbildungszeit dar, in der medizinisches Wissen konsequent in ärztliche Kompetenzen umgewandelt werden soll. Seit Novellierung der Ärztlichen Approbationsordnung (ÄApprO) vom 17. Juli 2012 sind ab 1. April 2013 die deutschen Universitäten verpflichtet, einen Ausbildungsplan in Form von PJ-Logbüchern für das Praktische Jahr in den Pflichttertialen Chirurgie und Innere Medizin bereitzustellen. In Vorbereitung dieser Neuerung hat der Medizinische Fakultätentag (MFT) im Juni 2012 Basis-Logbücher als Konsensusdokumente vorgelegt. An der Medizinischen Fakultät der Universität Magdeburg wird zur Ausbildung der PJ-Studierenden im Fach Chirurgie ein klinikspezifisches und in Eigeninitiative entwickeltes Portfolio genutzt. Es wurde überarbeitet und zu einem konkretisierten, alltagsbezogenen und stark klinisch orientierten, fakultätsspezifischen PJ-Logbuch nach Vorgabe des MFT umgestaltet. Ziel dieses des MFT und ist gleichzeitig an die Gegebenheiten und die Lehre der Magdeburger Medizinischen Fakultät angepasst. Den Studierenden wird ein alltagsbezogenes, klinisch relevantes Dokument an die Hand gegeben, um gemeinsam mit einem schlüssigen Ausbildungskonzept unverzichtbare praktisch-klinische Kompetenzen zu erwerben.BACKGROUND UW Medicine was one of the first health systems to encounter and treat COVID-19 patients in the United States, starting in late February 2020. OBJECTIVE Here we describe the rapid rollout of capabilities by UW Medicine Information Technology Services (ITS) to support our clinical response to the COVID-19 pandemic and provide recommendations for health systems to urgently consider, as they plan their own response to this and potentially other future pandemics. METHODS Our recommendations include establishing a hospital incident command structure that includes tight integration with IT, creating automated dashboards for incident command, optimizing emergency communication to staff and patients, and preparing human resources, security, other policies, and equipment to support the transition of all nonessential staff to telework.We describe how UW Medicine quickly expanded telemedicine capabilities to include most primary care providers and increasing numbers of specialty providers. We look at how we managed expedited change control processes to quickly update electronic health records (EHR) with new COVID-19 laboratory and clinical workflows. We also examine the integration of new technology such as tele-intensive care (ICU) equipment and improved integration with teleconferencing software into our EHR. To support the rapid preparation for COVID-19 at other health systems, we include samples of the UW Medicine's COVID-19 order set, COVID-19 documentation template, dashboard metric categories, and a list of the top 10 things your health care IT organization can do now to prepare. CONCLUSION The COVID-19 response requires new and expedited ways of approaching ITS support to clinical needs. UW Medicine ITS leadership hope that by quickly sharing our nimble response to clinical and operational requests, we can help other systems prepare to respond to this public health emergency. Georg Thieme Verlag KG Stuttgart · New York.BACKGROUND  With the consequences of inadequate dosing ranging from increased bleeding risk to excessive drug costs and undesirable administration regimens, the antihemophilic factors are uniquely suited to dose individualization. However, existing options for individualization are limited and exist outside the flow of care. We developed clinical decision support (CDS) software that is integrated with our electronic health record (EHR) and designed to streamline the process for our hematology providers. OBJECTIVES  The aim of this study is to develop and examine the usability of a CDS tool for antihemophilic factor dose individualization. METHODS  Our development strategy was based on the features associated with successful CDS tools and driven by a formal requirements analysis. The back-end code was based on algorithms developed for manual individualization and unit tested with 23,000 simulated patient profiles created from the range of patient-derived pharmacokinetic parameter estimates defined in children and adults.
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  • UAS surveys accurately identified areas of high mangrove cover using both standard and multispectral imagery, although derived index values for this vegetation class were only moderately correlated with ground measurements (R2 = 0.17-0.38) at their most informative scales. Conclusion These findings highlight the complex operational challenges that affect coastal mosquito control in heterogeneous environments. The problem is exacerbated by continued mangrove transgression into saltmarsh habitat in the region. Emerging UAS technology can help operators optimize treatments by accurately identifying and mapping challenging canopy cover using both standard and multispectral imaging.Patients receiving clinical genetics services often navigate emotionally difficult situations and may utilize their faith as a source of support, an aid in decision-making, or a core coping strategy. Although patients have expressed interest in discussing their religious or spiritual (R/S) beliefs with their genetic counselor (GC), GCs may avoid such conversations because they feel they do not have the necessary skills to discuss R/S beliefs (Reis, Baumiller, Scrivener, Yager, & Warren, 2007). This qualitative study explored how GC programs in North America currently prepare their students to discuss R/S matters with their patients. The aims of this study were to identify (1) the R/S topics genetic counseling programs currently cover in the curriculum, (2) how genetic counseling programs evaluate their students within the R/S topics and activities that are included in the curriculum, and (3) the value or importance placed on R/S training by genetic counseling program directors. Leaders of 12 (36%) of the 33 eligible GC programs at the time of the study participated in a semi-structured phone interview. Their responses were coded using open and axial coding techniques and analyzed using grounded theory. Results revealed that R/S issues are often covered during the psychosocial portions of the curriculum through writing assignments, in class exercises, and role plays. Almost all participating programs include information on pastoral care services, but have little to no training about specific R/S beliefs or the use of spiritual surveys. While participating program directors emphasized that it is critical for students to be prepared to hold conversations about patients' R/S beliefs, the strategies used to prepare students are inconsistent and often not evaluated. We provide suggestions for enriching the R/S training in genetic counseling graduate programs in order to prepare students to facilitate discussions around patients' religion and/or spirituality in genetic counseling sessions.This case study examined the influence of a surgical metal implant on the bioelectrical impedance analysis (BIA) readings of an athlete. Single-frequency BIA using a tetrapolar electrode configuration was applied to both the right and left sides of a 23-year-old female jumper who had an 8 × 345 mm titanium alloy nail implanted in her left tibia. The metal implant reduced BIA resistance and reactance on the implanted side by 27 and 6 ohms, respectively. This reduction in impedance resulted in a 0.4 kg-1.9 kg increase in the estimate of fat-free mass (FFM) depending on the prediction formula used. There was a concomitant decrease in the estimate of body fat percentage (%BF) with the underestimation ranging from 0.6% to 2.7% BF depending on the prediction formula. A metal implant of substantial size can alter the BIA reading. Technicians should apply BIA to the opposite side of the body when athletes present with a surgical implant in a limb.The investigation of the association between alexithymia and quality of life in infertility is a relatively neglected area of research. The aim of this study was to evaluate the association between alexithymia and infertility-related quality of life in women during Assisted Reproductive Treatment. https://www.selleckchem.com/products/gcn2-in-1.html Data were collected in a clinic in Rome, 93 infertile women completed the 20-item Toronto Alexithymia Scale (TAS-20), the Fertility Quality of Life (FertiQoL) questionnaire and a socio-demographic questionnaire. TAS-20 total and two factors - Difficulty in Identifying Feelings (DIF) and Difficulty in Describing Feelings (DDF) - showed significant negative correlations with the overall questionnaire and with both Core and Treatment modules of FertiQoL. The regression model explained the 43% variance in FertiQol overall scores (R2 =0.43; adjusted R2 =.38); a significant effect was reported for the number of previous attempts (beta=0.20; p less then .04), TAS-20 DIF (beta=-0.47; p less then .001) and TAS-20 Externally Orientated Thinking (EOT) (beta=0.20; p less then .04); after applying Benjamini-Hochberg correction procedure only TAS-20 DIF maintained its significance. Alexithymia is associated with a worsened quality of life in infertile women; specifically, low difficulties in identifying feelings were associated to higher quality of life. Further investigations are needed also to develop specific therapeutic interventions aimed to promote emotional abilities in infertile people. This article is protected by copyright. All rights reserved.Background Death notification can be challenging for emergency medicine physicians, who have no prior established relationship with the patient or their families. The GRIEV_ING death notification curriculum was developed to facilitate the delivery of the bad news of a patient's death and has been shown to improve learners' confidence and competence in death notification. Rapid-cycle deliberate practice (RCDP), a facilitator-guided, within-event debriefing technique, has demonstrated an improvement in learners' skills in a safe learning environment. The aim of this study was to identify whether the use of this technique is an effective method of teaching the GRIEV_ING curriculum, as demonstrated by learners' improved confidence, cognitive knowledge and performance. Rapid-cycle deliberate practice (RCDP), a facilitator-guided within-event, debriefing technique, has demonstrated an improvement in learners' skills in a safe learning environment METHODS A 4-hour pilot curriculum was developed to educate and assess residents on the delivery of death notification.
    UAS surveys accurately identified areas of high mangrove cover using both standard and multispectral imagery, although derived index values for this vegetation class were only moderately correlated with ground measurements (R2 = 0.17-0.38) at their most informative scales. Conclusion These findings highlight the complex operational challenges that affect coastal mosquito control in heterogeneous environments. The problem is exacerbated by continued mangrove transgression into saltmarsh habitat in the region. Emerging UAS technology can help operators optimize treatments by accurately identifying and mapping challenging canopy cover using both standard and multispectral imaging.Patients receiving clinical genetics services often navigate emotionally difficult situations and may utilize their faith as a source of support, an aid in decision-making, or a core coping strategy. Although patients have expressed interest in discussing their religious or spiritual (R/S) beliefs with their genetic counselor (GC), GCs may avoid such conversations because they feel they do not have the necessary skills to discuss R/S beliefs (Reis, Baumiller, Scrivener, Yager, & Warren, 2007). This qualitative study explored how GC programs in North America currently prepare their students to discuss R/S matters with their patients. The aims of this study were to identify (1) the R/S topics genetic counseling programs currently cover in the curriculum, (2) how genetic counseling programs evaluate their students within the R/S topics and activities that are included in the curriculum, and (3) the value or importance placed on R/S training by genetic counseling program directors. Leaders of 12 (36%) of the 33 eligible GC programs at the time of the study participated in a semi-structured phone interview. Their responses were coded using open and axial coding techniques and analyzed using grounded theory. Results revealed that R/S issues are often covered during the psychosocial portions of the curriculum through writing assignments, in class exercises, and role plays. Almost all participating programs include information on pastoral care services, but have little to no training about specific R/S beliefs or the use of spiritual surveys. While participating program directors emphasized that it is critical for students to be prepared to hold conversations about patients' R/S beliefs, the strategies used to prepare students are inconsistent and often not evaluated. We provide suggestions for enriching the R/S training in genetic counseling graduate programs in order to prepare students to facilitate discussions around patients' religion and/or spirituality in genetic counseling sessions.This case study examined the influence of a surgical metal implant on the bioelectrical impedance analysis (BIA) readings of an athlete. Single-frequency BIA using a tetrapolar electrode configuration was applied to both the right and left sides of a 23-year-old female jumper who had an 8 × 345 mm titanium alloy nail implanted in her left tibia. The metal implant reduced BIA resistance and reactance on the implanted side by 27 and 6 ohms, respectively. This reduction in impedance resulted in a 0.4 kg-1.9 kg increase in the estimate of fat-free mass (FFM) depending on the prediction formula used. There was a concomitant decrease in the estimate of body fat percentage (%BF) with the underestimation ranging from 0.6% to 2.7% BF depending on the prediction formula. A metal implant of substantial size can alter the BIA reading. Technicians should apply BIA to the opposite side of the body when athletes present with a surgical implant in a limb.The investigation of the association between alexithymia and quality of life in infertility is a relatively neglected area of research. The aim of this study was to evaluate the association between alexithymia and infertility-related quality of life in women during Assisted Reproductive Treatment. https://www.selleckchem.com/products/gcn2-in-1.html Data were collected in a clinic in Rome, 93 infertile women completed the 20-item Toronto Alexithymia Scale (TAS-20), the Fertility Quality of Life (FertiQoL) questionnaire and a socio-demographic questionnaire. TAS-20 total and two factors - Difficulty in Identifying Feelings (DIF) and Difficulty in Describing Feelings (DDF) - showed significant negative correlations with the overall questionnaire and with both Core and Treatment modules of FertiQoL. The regression model explained the 43% variance in FertiQol overall scores (R2 =0.43; adjusted R2 =.38); a significant effect was reported for the number of previous attempts (beta=0.20; p less then .04), TAS-20 DIF (beta=-0.47; p less then .001) and TAS-20 Externally Orientated Thinking (EOT) (beta=0.20; p less then .04); after applying Benjamini-Hochberg correction procedure only TAS-20 DIF maintained its significance. Alexithymia is associated with a worsened quality of life in infertile women; specifically, low difficulties in identifying feelings were associated to higher quality of life. Further investigations are needed also to develop specific therapeutic interventions aimed to promote emotional abilities in infertile people. This article is protected by copyright. All rights reserved.Background Death notification can be challenging for emergency medicine physicians, who have no prior established relationship with the patient or their families. The GRIEV_ING death notification curriculum was developed to facilitate the delivery of the bad news of a patient's death and has been shown to improve learners' confidence and competence in death notification. Rapid-cycle deliberate practice (RCDP), a facilitator-guided, within-event debriefing technique, has demonstrated an improvement in learners' skills in a safe learning environment. The aim of this study was to identify whether the use of this technique is an effective method of teaching the GRIEV_ING curriculum, as demonstrated by learners' improved confidence, cognitive knowledge and performance. Rapid-cycle deliberate practice (RCDP), a facilitator-guided within-event, debriefing technique, has demonstrated an improvement in learners' skills in a safe learning environment METHODS A 4-hour pilot curriculum was developed to educate and assess residents on the delivery of death notification.
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  • An accurate prediction of atomic diffusion in Fe alloys is challenging due to thermal magnetic excitations and magnetic transitions. We propose an efficient approach to address these properties via a Monte Carlo simulation, using ab initio-based effective interaction models. The temperature evolution of self- and Cu diffusion coefficients in α-iron are successfully predicted, particularly the diffusion acceleration around the Curie point, which requires a quantum treatment of spins. We point out a dominance of magnetic disorder over chemical effects on diffusion in the very dilute systems.Computer simulations of the fluid-to-solid phase transition in the hard sphere system were instrumental for our understanding of crystallization processes. But while colloid experiments and theory have been predicting the stability of several binary hard sphere crystals for many years, simulations were not successful to confirm this phenomenon. Here, we report the growth of binary hard sphere crystals isostructural to Laves phases, AlB_2, and NaZn_13 in simulation directly from the fluid. We analyze particle kinetics during Laves phase growth using event-driven molecular dynamics simulations with and without swap moves that speed up diffusion. The crystallization process transitions from nucleation and growth to spinodal decomposition already deep within the fluid-solid coexistence regime. Finally, we present packing fraction-size ratio state diagrams in the vicinity of the stability regions of three binary crystals.Higher-order topological insulators (HOTIs) have emerged as a new class of phases, whose robust in-gap "corner" modes arise from the bulk higher-order multipoles beyond the dipoles in conventional topological insulators. Here, we incorporate Floquet driving into HOTIs, and report for the first time a dynamical polarization theory with anomalous nonequilibrium multipoles. Further, a proposal to detect not only corner states but also their dynamical origin in cold atoms is demonstrated, with the latter one never achieved before. Experimental determination of anomalous Floquet corner modes is also proposed.A novel method to calculate mode Grüneisen parameters of a material from first principles is presented. https://www.selleckchem.com/products/Staurosporine.html This method overcomes the difficulties and limitations of existing approaches, based on the calculation of either third-order force constants or phonon frequencies at different volumes. Our method requires the calculation of phonon frequencies of a material at only the volume of interest, it is based on the second-order differentiation of a corrected stress tensor with respect to normal mode coordinates, and it yields simultaneously all the components of the mode Grüneisen parameters tensor. In this work, after discussing conceptual and technical aspects, the method is applied to silicon, aluminum, scandium fluoride, and a metallic alloy. These calculations show that our method is straightforward and it is suited to be applied to the broad class of materials prone to exhibit structural instabilities, or presenting anisotropy, or chemical and/or structural disorder.We consider the number N_θ_A(θ) of eigenvalues e^iθ_j of a random unitary matrix, drawn from CUE_β(N), in the interval θ_j∈[θ_A,θ]. The deviations from its mean, N_θ_A(θ)-E[N_θ_A(θ)], form a random process as function of θ. We study the maximum of this process, by exploiting the mapping onto the statistical mechanics of log-correlated random landscapes. By using an extended Fisher-Hartwig conjecture supplemented with the freezing duality conjecture for log-correlated fields, we obtain the cumulants of the distribution of that maximum for any β>0. It exhibits combined features of standard counting statistics of fermions (free for β=2 and with Sutherland-type interaction for β≠2) in an interval and extremal statistics of the fractional Brownian motion with Hurst index H=0. The β=2 results are expected to apply to the statistics of zeroes of the Riemann Zeta function.We present a microwave electron spin resonance study of the quantum spin dimer system TlCuCl_3, which shows the magnetic-field-induced ordering with both antiferromagnetic spin order and ferroelectricity by the Bose-Einstein condensation (BEC) of triplon quasiparticles. Our main achievement is an electrical switching of the nonreciprocal directional microwave response in the triplon ****phase. High-speed directional control of microwave absorption by applying an electric field has been accomplished in this Letter. The strength of the observed nonreciprocal microwave response well agrees with the calculation based on Kubo theory with the parameters, evaluated from the static electric polarization in this material.We show the directional dichroism in a collinear antiferromagnet MnTiO_3. The dichroism between two distinctive antiferromagnetic states with opposite signs of staggered magnetic moments can be regarded as magnetochiral dichroism in the absence of external fields. Electric-field reversal of antiferromagnetic domain causes a change in the absorption intensity of unpolarized light around 2.15 eV. The difference in optical absorption between two antiferromagnetic states is reversed for the light propagating in the opposite direction. The absorption coefficient displays a hysteretic behavior for a cycle of sweeping the external electric or magnetic field.A search for the decays B_s^0→e^+e^- and B^0→e^+e^- is performed using data collected with the LHCb experiment in proton-proton collisions at center-of-mass energies of 7, 8, and 13 TeV, corresponding to integrated luminosities of 1, 2, and 2 fb^-1, respectively. No signal is observed. Assuming no contribution from B^0→e^+e^- decays, an upper limit on the branching fraction B(B_s^0→e^+e^-) less then 9.4(11.2)×10^-9 is obtained at 90(95)% confidence level. If no B_s^0→e^+e^- contribution is assumed, a limit of B(B^0→e^+e^-) less then 2.5(3.0)×10^-9 is determined at 90(95)% confidence level. These upper limits are more than one order of magnitude lower than the previous values.
    An accurate prediction of atomic diffusion in Fe alloys is challenging due to thermal magnetic excitations and magnetic transitions. We propose an efficient approach to address these properties via a Monte Carlo simulation, using ab initio-based effective interaction models. The temperature evolution of self- and Cu diffusion coefficients in α-iron are successfully predicted, particularly the diffusion acceleration around the Curie point, which requires a quantum treatment of spins. We point out a dominance of magnetic disorder over chemical effects on diffusion in the very dilute systems.Computer simulations of the fluid-to-solid phase transition in the hard sphere system were instrumental for our understanding of crystallization processes. But while colloid experiments and theory have been predicting the stability of several binary hard sphere crystals for many years, simulations were not successful to confirm this phenomenon. Here, we report the growth of binary hard sphere crystals isostructural to Laves phases, AlB_2, and NaZn_13 in simulation directly from the fluid. We analyze particle kinetics during Laves phase growth using event-driven molecular dynamics simulations with and without swap moves that speed up diffusion. The crystallization process transitions from nucleation and growth to spinodal decomposition already deep within the fluid-solid coexistence regime. Finally, we present packing fraction-size ratio state diagrams in the vicinity of the stability regions of three binary crystals.Higher-order topological insulators (HOTIs) have emerged as a new class of phases, whose robust in-gap "corner" modes arise from the bulk higher-order multipoles beyond the dipoles in conventional topological insulators. Here, we incorporate Floquet driving into HOTIs, and report for the first time a dynamical polarization theory with anomalous nonequilibrium multipoles. Further, a proposal to detect not only corner states but also their dynamical origin in cold atoms is demonstrated, with the latter one never achieved before. Experimental determination of anomalous Floquet corner modes is also proposed.A novel method to calculate mode Grüneisen parameters of a material from first principles is presented. https://www.selleckchem.com/products/Staurosporine.html This method overcomes the difficulties and limitations of existing approaches, based on the calculation of either third-order force constants or phonon frequencies at different volumes. Our method requires the calculation of phonon frequencies of a material at only the volume of interest, it is based on the second-order differentiation of a corrected stress tensor with respect to normal mode coordinates, and it yields simultaneously all the components of the mode Grüneisen parameters tensor. In this work, after discussing conceptual and technical aspects, the method is applied to silicon, aluminum, scandium fluoride, and a metallic alloy. These calculations show that our method is straightforward and it is suited to be applied to the broad class of materials prone to exhibit structural instabilities, or presenting anisotropy, or chemical and/or structural disorder.We consider the number N_θ_A(θ) of eigenvalues e^iθ_j of a random unitary matrix, drawn from CUE_β(N), in the interval θ_j∈[θ_A,θ]. The deviations from its mean, N_θ_A(θ)-E[N_θ_A(θ)], form a random process as function of θ. We study the maximum of this process, by exploiting the mapping onto the statistical mechanics of log-correlated random landscapes. By using an extended Fisher-Hartwig conjecture supplemented with the freezing duality conjecture for log-correlated fields, we obtain the cumulants of the distribution of that maximum for any β>0. It exhibits combined features of standard counting statistics of fermions (free for β=2 and with Sutherland-type interaction for β≠2) in an interval and extremal statistics of the fractional Brownian motion with Hurst index H=0. The β=2 results are expected to apply to the statistics of zeroes of the Riemann Zeta function.We present a microwave electron spin resonance study of the quantum spin dimer system TlCuCl_3, which shows the magnetic-field-induced ordering with both antiferromagnetic spin order and ferroelectricity by the Bose-Einstein condensation (BEC) of triplon quasiparticles. Our main achievement is an electrical switching of the nonreciprocal directional microwave response in the triplon BEC phase. High-speed directional control of microwave absorption by applying an electric field has been accomplished in this Letter. The strength of the observed nonreciprocal microwave response well agrees with the calculation based on Kubo theory with the parameters, evaluated from the static electric polarization in this material.We show the directional dichroism in a collinear antiferromagnet MnTiO_3. The dichroism between two distinctive antiferromagnetic states with opposite signs of staggered magnetic moments can be regarded as magnetochiral dichroism in the absence of external fields. Electric-field reversal of antiferromagnetic domain causes a change in the absorption intensity of unpolarized light around 2.15 eV. The difference in optical absorption between two antiferromagnetic states is reversed for the light propagating in the opposite direction. The absorption coefficient displays a hysteretic behavior for a cycle of sweeping the external electric or magnetic field.A search for the decays B_s^0→e^+e^- and B^0→e^+e^- is performed using data collected with the LHCb experiment in proton-proton collisions at center-of-mass energies of 7, 8, and 13 TeV, corresponding to integrated luminosities of 1, 2, and 2 fb^-1, respectively. No signal is observed. Assuming no contribution from B^0→e^+e^- decays, an upper limit on the branching fraction B(B_s^0→e^+e^-) less then 9.4(11.2)×10^-9 is obtained at 90(95)% confidence level. If no B_s^0→e^+e^- contribution is assumed, a limit of B(B^0→e^+e^-) less then 2.5(3.0)×10^-9 is determined at 90(95)% confidence level. These upper limits are more than one order of magnitude lower than the previous values.
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