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  • In MoS2 trilayers, our experiments uncovered two types of interlayer excitons with and without in-built electric dipoles. Highly tunable excitonic transitions with large in-built dipoles and oscillator strengths will result in strong exciton-exciton interactions and therefore hold great promise for non-linear optics with polaritons.Nanoscale lithography and information storage in biocompatible materials offer possibilities for applications such as bioelectronics and degradable electronics for which traditional semiconductor fabrication techniques cannot be used. Silk fibroin, a natural protein renowned for its strength and biocompatibility, has been widely studied in this context. Here, we present the use of silk film as a biofunctional medium for nanolithography and data storage. Using tip-enhanced near-field infrared nanolithography, we demonstrate versatile manipulation and characterize the topography and conformation of the silk in situ. In particular, we fabricate greyscale and dual-tone nanopatterns with full-width at half-maximum resolutions of ~35 nm, creating an erasable 'silk drive' that digital data can be written to or read from. As an optical storage medium, the silk drive can store digital and biological information with a capacity of ~64 GB inch-2 and exhibits long-term stability under various harsh conditions. As a proof-of-principle demonstration, we show that this silk drive can be biofunctionalized to exhibit chromogenic reactions, resistance to bacterial infection and heat-triggered, enzyme-assisted decomposition.The progress of plasmon-based technologies relies on an understanding of the properties of the enhanced electromagnetic fields generated by the coupling nanostrucutres1-6. Plasmon-enhanced applications include advanced spectroscopies7-10, optomechanics11, optomagnetics12 and biosensing13-17. However, precise determination of plasmon field intensity distribution within a nanogap remains challenging. Here, we demonstrate a molecular ruler made from a set of viologen-based, self-assembly monolayers with which we precisely measures field distribution within a plasmon nanocavity with ~2-Å spatial resolution. We observed an unusually large plasmon field intensity inhomogeneity that we attribute to the formation of a plasmonic comb in the nanocavity. As a consequence, we posit that the generally adopted continuous media approximation for molecular monolayers should be used carefully.There have been many attempts to visualize the inflamed joints using multiphoton microscopy. However, due to the hypervascular and multilayered structure of the inflamed synovium, intravital imaging of the deep synovial tissue has been difficult. Here, we established original intravital imaging systems to visualize synovial tissue and pathological osteoclasts at the pannus-bone interface using multiphoton microscopy. Combined with fluorescence-labeling of CTLA-4 Ig, a biological agent used for the treatment of rheumatoid arthritis, we identified that CTLA-4 Ig was distributed predominantly within the inflamed synovium and bound to CX3CR1+ macrophages and CD140a+ fibroblasts 6 h after injection, but not to mature osteoclasts. Intravital imaging of blood and lymphatic vessels in the inflamed synovium further showed that extravasated CTLA-4 Ig was immediately drained through lymphatic vessels under acute arthritic conditions, but the drainage activity was retarded under chronic conditions. These results indicate that this intravital synovial imaging system can serve as a platform for exploring the dynamics of immune cells, osteoclasts, and biological agents within the synovial microenvironment in vivo.We use aggregated and anonymized information based on international expenditures through corporate payment cards to map the network of global business travel. We combine this network with information on the industrial composition and export baskets of national economies. https://www.selleckchem.com/products/S31-201.html The business travel network helps to predict which economic activities will grow in a country, which new activities will develop and which old activities will be abandoned. In statistical terms, business travel has the most substantial impact among a range of bilateral relationships between countries, such as trade, foreign direct investments and migration. Moreover, our analysis suggests that this impact is causal business travel from countries specializing in a specific industry causes growth in that economic activity in the destination country. Our interpretation of this is that business travel helps to diffuse knowledge, and we use our estimates to assess which countries contribute or benefit the most from the diffusion of knowledge through global business travel.If the structure of language vocabularies mirrors the structure of natural divisions that are universally perceived, then the meanings of words in different languages should closely align. By contrast, if shared word meanings are a product of shared culture, history and geography, they may differ between languages in substantial but predictable ways. Here, we analysed the semantic neighbourhoods of 1,010 meanings in 41 languages. The most-aligned words were from semantic domains with high internal structure (number, quantity and kinship). Words denoting natural kinds, common actions and artefacts aligned **** less well. Languages that are more geographically proximate, more historically related and/or spoken by more-similar cultures had more aligned word meanings. These results provide evidence that the meanings of common words vary in ways that reflect the culture, history and geography of their users.The groundwater crisis in northwestern India is the result of over-exploitation of groundwater resources for irrigation. The Government of India has targeted a 20 percent improvement in irrigation groundwater use efficiency. In this perspective, and using a regional-scale calibrated and validated three-dimensional groundwater flow model, this article provides the first forecasts of water levels in the study area up to the year 2028, both with and without this improvement in use efficiency. Future water levels without any mitigation efforts are anticipated to decline by up to 2.8 m/year in some areas. A simulation with a 20 percent reduction in groundwater abstraction shows spatially varied aquifer responses. Tangible results are visible in a decade, and the water-level decline rates decrease by 36-67 percent in over-exploited areas. Although increasing irrigation use efficiency provides tangible benefits, an integrated approach to agricultural water management practice that incorporates use efficiency along with other measures like water-efficient cropping patterns and rainwater harvesting may yield better results in a shorter period.
    In MoS2 trilayers, our experiments uncovered two types of interlayer excitons with and without in-built electric dipoles. Highly tunable excitonic transitions with large in-built dipoles and oscillator strengths will result in strong exciton-exciton interactions and therefore hold great promise for non-linear optics with polaritons.Nanoscale lithography and information storage in biocompatible materials offer possibilities for applications such as bioelectronics and degradable electronics for which traditional semiconductor fabrication techniques cannot be used. Silk fibroin, a natural protein renowned for its strength and biocompatibility, has been widely studied in this context. Here, we present the use of silk film as a biofunctional medium for nanolithography and data storage. Using tip-enhanced near-field infrared nanolithography, we demonstrate versatile manipulation and characterize the topography and conformation of the silk in situ. In particular, we fabricate greyscale and dual-tone nanopatterns with full-width at half-maximum resolutions of ~35 nm, creating an erasable 'silk drive' that digital data can be written to or read from. As an optical storage medium, the silk drive can store digital and biological information with a capacity of ~64 GB inch-2 and exhibits long-term stability under various harsh conditions. As a proof-of-principle demonstration, we show that this silk drive can be biofunctionalized to exhibit chromogenic reactions, resistance to bacterial infection and heat-triggered, enzyme-assisted decomposition.The progress of plasmon-based technologies relies on an understanding of the properties of the enhanced electromagnetic fields generated by the coupling nanostrucutres1-6. Plasmon-enhanced applications include advanced spectroscopies7-10, optomechanics11, optomagnetics12 and biosensing13-17. However, precise determination of plasmon field intensity distribution within a nanogap remains challenging. Here, we demonstrate a molecular ruler made from a set of viologen-based, self-assembly monolayers with which we precisely measures field distribution within a plasmon nanocavity with ~2-Å spatial resolution. We observed an unusually large plasmon field intensity inhomogeneity that we attribute to the formation of a plasmonic comb in the nanocavity. As a consequence, we posit that the generally adopted continuous media approximation for molecular monolayers should be used carefully.There have been many attempts to visualize the inflamed joints using multiphoton microscopy. However, due to the hypervascular and multilayered structure of the inflamed synovium, intravital imaging of the deep synovial tissue has been difficult. Here, we established original intravital imaging systems to visualize synovial tissue and pathological osteoclasts at the pannus-bone interface using multiphoton microscopy. Combined with fluorescence-labeling of CTLA-4 Ig, a biological agent used for the treatment of rheumatoid arthritis, we identified that CTLA-4 Ig was distributed predominantly within the inflamed synovium and bound to CX3CR1+ macrophages and CD140a+ fibroblasts 6 h after injection, but not to mature osteoclasts. Intravital imaging of blood and lymphatic vessels in the inflamed synovium further showed that extravasated CTLA-4 Ig was immediately drained through lymphatic vessels under acute arthritic conditions, but the drainage activity was retarded under chronic conditions. These results indicate that this intravital synovial imaging system can serve as a platform for exploring the dynamics of immune cells, osteoclasts, and biological agents within the synovial microenvironment in vivo.We use aggregated and anonymized information based on international expenditures through corporate payment cards to map the network of global business travel. We combine this network with information on the industrial composition and export baskets of national economies. https://www.selleckchem.com/products/S31-201.html The business travel network helps to predict which economic activities will grow in a country, which new activities will develop and which old activities will be abandoned. In statistical terms, business travel has the most substantial impact among a range of bilateral relationships between countries, such as trade, foreign direct investments and migration. Moreover, our analysis suggests that this impact is causal business travel from countries specializing in a specific industry causes growth in that economic activity in the destination country. Our interpretation of this is that business travel helps to diffuse knowledge, and we use our estimates to assess which countries contribute or benefit the most from the diffusion of knowledge through global business travel.If the structure of language vocabularies mirrors the structure of natural divisions that are universally perceived, then the meanings of words in different languages should closely align. By contrast, if shared word meanings are a product of shared culture, history and geography, they may differ between languages in substantial but predictable ways. Here, we analysed the semantic neighbourhoods of 1,010 meanings in 41 languages. The most-aligned words were from semantic domains with high internal structure (number, quantity and kinship). Words denoting natural kinds, common actions and artefacts aligned much less well. Languages that are more geographically proximate, more historically related and/or spoken by more-similar cultures had more aligned word meanings. These results provide evidence that the meanings of common words vary in ways that reflect the culture, history and geography of their users.The groundwater crisis in northwestern India is the result of over-exploitation of groundwater resources for irrigation. The Government of India has targeted a 20 percent improvement in irrigation groundwater use efficiency. In this perspective, and using a regional-scale calibrated and validated three-dimensional groundwater flow model, this article provides the first forecasts of water levels in the study area up to the year 2028, both with and without this improvement in use efficiency. Future water levels without any mitigation efforts are anticipated to decline by up to 2.8 m/year in some areas. A simulation with a 20 percent reduction in groundwater abstraction shows spatially varied aquifer responses. Tangible results are visible in a decade, and the water-level decline rates decrease by 36-67 percent in over-exploited areas. Although increasing irrigation use efficiency provides tangible benefits, an integrated approach to agricultural water management practice that incorporates use efficiency along with other measures like water-efficient cropping patterns and rainwater harvesting may yield better results in a shorter period.
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  • AIM Parents' role as end-of-life decision-makers for their child has become largely accepted Western health-care practice. How parents subsequently view and live with the end-of-life decision (ELD) they made has not been extensively examined. To help extend understanding of this phenomenon and contribute to care, as a part of a study on end-of-life decision-making, bereaved parents were asked about the aftermath of their decision-making. METHODS A qualitative methodology was used. Semi-structured interviews were conducted with parents who had discussed ELDs for their child who had a life-limiting condition and had died. Data were thematically analysed. RESULTS Twenty-five bereaved parents participated. Results indicate that parents hold multi-faceted views about their decision-making experiences. https://www.selleckchem.com/products/bb-94.html An ELD was viewed as weighty in nature, with decisions judged against the circumstances that the child and parents found themselves in. Despite the weightiness, parents reflected positively on their decisions, regarding themselves as making the right decision. Consequently, parents' comments demonstrated being able to live with their decision. When expressed, regret related to needing an ELD, rather than the actual decision. The few parents who did not perceive themselves as their child's decision-maker subsequently articulated negative reactions. Enduring concerns held by some parents mostly related to non-decisional matters, such as the child's suffering or not knowing the cause of death. CONCLUSION Results suggest that parents can live well with the ELDs they made for their child. End-of-life decision-making knowledge is confirmed and extended, and clinical support for parents informed. © 2020 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).The lipopolysaccharide (LPS) O-antigen structure of the plant pathogen Rhizobium radiobacter strain TT9 and its possible role in a plant-microbe interaction was investigated. The analyses disclosed the presence of two O-antigens, named Poly1 and Poly2. The repetitive unit of Poly2 constitutes a 4-α-l-rhamnose linked to a 3-α-d-fucose residue. Surprisingly, Poly1 turned out to be a novel type of biopolymer in which the repeating unit is formed by a monosaccharide and an amino-acid derivative, so that the polymer has alternating glycosidic and amidic bonds joining the two units 4-amino-4-deoxy-3-O-methyl-d-fucose and (2'R,3'R,4'S)-N-methyl-3',4'-dihydroxy-3'-methyl-5'-oxoproline). Differently from the O-antigens of LPSs from other pathogenic Gram-negative bacteria, these two O-antigens do not activate the oxidative burst, an early innate immune response in the model plant Arabidopsis thaliana, explaining at least in part the ability of this R. radiobacter strain to avoid host defenses during a plant infection process. © 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.The catalytic diastereodivergent construction of stereoisomers having two or more stereogenic centers has been extensively studied. In contrast, the switchable introduction of another stereogenic element, that is, Z/E configuration involving a polysubstituted alkene group, into the optically active stereoisomers, has not been recognized yet. Disclosed here is the pseudo-stereodivergent synthesis of highly enantioenriched tetrasubstituted alkene architectures from isatin-based Morita-Baylis-Hillman carbonates and allylic derivatives, under the cooperative catalysis of a tertiary amine and a chiral iridium complex. The success of the switchable construction of the tetrasubstituted alkene motif relies on the diastereodivergent 1,3-oxo-allylation reaction between N-allylic ylides and chiral π-allyliridium complex intermediates by ligand and substrate control, followed by the stereoselective concerted 3,3-Cope rearrangement process. © 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.Stress and anxiety pose a threat to college students' academic performance as well as their long-term mental and physical health, but the time constraints of a rigorous academic schedule make it difficult to offer even brief mental health interventions. A convenience sample of full-time students at a public university was recruited for a 5-week study conducted mostly using an online platform. Participants were randomly assigned to a Mindfulness-Based Art Therapy (MBAT) intervention or a Neutral Clay Task (NCT). Anxiety, perceived stress, and salivary cortisol outcomes were measured. A total of n = 77 participants completed the study. The MBAT group experienced significant reductions in anxiety and perceived stress compared to the NCT group. Significant reductions in salivary cortisol were observed, but only time could be identified as a confounding variable. Art making alone is not enough to induce significant positive responses, but this study suggests MBAT can, and that an online intervention could offer feasible and accessible mental health services on college campuses. Further refinement of biological data collection and analysis is needed to determine what the mediating effects MBAT could have, if any, at the molecular level. © 2020 John Wiley & Sons, Ltd.Childhood trauma is associated with poor health outcomes in adulthood. Mechanisms for these associations are not well understood because past studies have focused predominantly on populations that have already developed physical and mental health problems. The present study examined the association between childhood trauma and stress-related vulnerability factors in a healthy adult sample (n = 79; 68% female, mean age = 27.5, SD = 6.5). Emotion regulation difficulties were examined as a potential mediator. Participants completed baseline laboratory assessments of reported childhood trauma, emotion regulation difficulties, prior month sleep quality, baseline impedance cardiography and behavioural tests of executive functioning (EF) and a three-day experience sampling assessment protocol that included sleep diary, reported and objective pre-sleep arousal, daily hassles and reported EF difficulties. Reported history of childhood abuse was significantly associated with difficulties in emotion regulation, self-report and objective pre-sleep arousal, diary-assessed sleep quality, daily hassles and reported EF difficulties.
    AIM Parents' role as end-of-life decision-makers for their child has become largely accepted Western health-care practice. How parents subsequently view and live with the end-of-life decision (ELD) they made has not been extensively examined. To help extend understanding of this phenomenon and contribute to care, as a part of a study on end-of-life decision-making, bereaved parents were asked about the aftermath of their decision-making. METHODS A qualitative methodology was used. Semi-structured interviews were conducted with parents who had discussed ELDs for their child who had a life-limiting condition and had died. Data were thematically analysed. RESULTS Twenty-five bereaved parents participated. Results indicate that parents hold multi-faceted views about their decision-making experiences. https://www.selleckchem.com/products/bb-94.html An ELD was viewed as weighty in nature, with decisions judged against the circumstances that the child and parents found themselves in. Despite the weightiness, parents reflected positively on their decisions, regarding themselves as making the right decision. Consequently, parents' comments demonstrated being able to live with their decision. When expressed, regret related to needing an ELD, rather than the actual decision. The few parents who did not perceive themselves as their child's decision-maker subsequently articulated negative reactions. Enduring concerns held by some parents mostly related to non-decisional matters, such as the child's suffering or not knowing the cause of death. CONCLUSION Results suggest that parents can live well with the ELDs they made for their child. End-of-life decision-making knowledge is confirmed and extended, and clinical support for parents informed. © 2020 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).The lipopolysaccharide (LPS) O-antigen structure of the plant pathogen Rhizobium radiobacter strain TT9 and its possible role in a plant-microbe interaction was investigated. The analyses disclosed the presence of two O-antigens, named Poly1 and Poly2. The repetitive unit of Poly2 constitutes a 4-α-l-rhamnose linked to a 3-α-d-fucose residue. Surprisingly, Poly1 turned out to be a novel type of biopolymer in which the repeating unit is formed by a monosaccharide and an amino-acid derivative, so that the polymer has alternating glycosidic and amidic bonds joining the two units 4-amino-4-deoxy-3-O-methyl-d-fucose and (2'R,3'R,4'S)-N-methyl-3',4'-dihydroxy-3'-methyl-5'-oxoproline). Differently from the O-antigens of LPSs from other pathogenic Gram-negative bacteria, these two O-antigens do not activate the oxidative burst, an early innate immune response in the model plant Arabidopsis thaliana, explaining at least in part the ability of this R. radiobacter strain to avoid host defenses during a plant infection process. © 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.The catalytic diastereodivergent construction of stereoisomers having two or more stereogenic centers has been extensively studied. In contrast, the switchable introduction of another stereogenic element, that is, Z/E configuration involving a polysubstituted alkene group, into the optically active stereoisomers, has not been recognized yet. Disclosed here is the pseudo-stereodivergent synthesis of highly enantioenriched tetrasubstituted alkene architectures from isatin-based Morita-Baylis-Hillman carbonates and allylic derivatives, under the cooperative catalysis of a tertiary amine and a chiral iridium complex. The success of the switchable construction of the tetrasubstituted alkene motif relies on the diastereodivergent 1,3-oxo-allylation reaction between N-allylic ylides and chiral π-allyliridium complex intermediates by ligand and substrate control, followed by the stereoselective concerted 3,3-Cope rearrangement process. © 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.Stress and anxiety pose a threat to college students' academic performance as well as their long-term mental and physical health, but the time constraints of a rigorous academic schedule make it difficult to offer even brief mental health interventions. A convenience sample of full-time students at a public university was recruited for a 5-week study conducted mostly using an online platform. Participants were randomly assigned to a Mindfulness-Based Art Therapy (MBAT) intervention or a Neutral Clay Task (NCT). Anxiety, perceived stress, and salivary cortisol outcomes were measured. A total of n = 77 participants completed the study. The MBAT group experienced significant reductions in anxiety and perceived stress compared to the NCT group. Significant reductions in salivary cortisol were observed, but only time could be identified as a confounding variable. Art making alone is not enough to induce significant positive responses, but this study suggests MBAT can, and that an online intervention could offer feasible and accessible mental health services on college campuses. Further refinement of biological data collection and analysis is needed to determine what the mediating effects MBAT could have, if any, at the molecular level. © 2020 John Wiley & Sons, Ltd.Childhood trauma is associated with poor health outcomes in adulthood. Mechanisms for these associations are not well understood because past studies have focused predominantly on populations that have already developed physical and mental health problems. The present study examined the association between childhood trauma and stress-related vulnerability factors in a healthy adult sample (n = 79; 68% female, mean age = 27.5, SD = 6.5). Emotion regulation difficulties were examined as a potential mediator. Participants completed baseline laboratory assessments of reported childhood trauma, emotion regulation difficulties, prior month sleep quality, baseline impedance cardiography and behavioural tests of executive functioning (EF) and a three-day experience sampling assessment protocol that included sleep diary, reported and objective pre-sleep arousal, daily hassles and reported EF difficulties. Reported history of childhood abuse was significantly associated with difficulties in emotion regulation, self-report and objective pre-sleep arousal, diary-assessed sleep quality, daily hassles and reported EF difficulties.
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  • thailandensis. **** immunized intranasally with individual AuNP-protein-LPS conjugates, showed variable degrees of protection against intranasal Bm infection, while an optimized combination formulation (containing protein antigens OmpW, OpcP, and Hemagglutinin, along with LPS) showed complete protection against lethality in a mouse model of inhalational glanders. Animals immunized with different nano-glycoconjugates showed robust antigen-specific antibody responses. Moreover, serum from animals immunized with the optimized nano-glycoconjugate formulation showed sustained antibody responses with increased serum-mediated inhibition of adherence and opsonophagocytic activity in vitro. This study provides the basis for the rational design and construction of a multicomponent vaccine platform against Bm.Sustained activation of NLRP3 inflammasome and release of neutrophil extracellular traps (NETs) impair wound healing of diabetic foot ulcers (DFUs). Our previous study reported that milk fat globule epidermal growth factor VIII (MFG-E8) attenuates tissue damage in systemic lupus erythematosus. However, the functional effect of MFG-E8 on "NLRP3 inflammasome-NETs" inflammatory loop in wound healing of diabetes is not completely elucidated. In this study, neutrophils from DFU patients are susceptible to undergo NETosis, releasing more NETs. The circulating levels of NET components neutrophil elastase and proteinase 3 and inflammatory cytokines IL-1β and IL-18 were significantly elevated in DFU patients compared with healthy controls or diabetic patients, in spite of higher levels of MFG-E8 in DFU patients. In Mfge8 -/- diabetic ****, skin wound displayed exaggerated inflammatory response, including leukocyte infiltration, excessive activation of NLRP3 inflammasome (release of higher IL-1β, IL-18, and TNF-α), largely lodged NETs, resulting in poor angiogenesis and wound closure. When stimulated with high-dose glucose or IL-18, MFG-E8-deficient neutrophils release more NETs than WT neutrophils. After administration of recombinant MFG-E8, IL-18-primed NETosis of WT or Mfge8 -/- neutrophils was significantly inhibited. Furthermore, NET and mCRAMP (component of NETs, the murine equivalent of cathelicidin LL-37 in human)-mediated activation of NLRP3 inflammasome and production of IL-1β/IL-18 were significantly elevated in Mfge8 -/- macrophages compared with WT macrophages, which were also significantly dampened by the administration of rmMFG-E8. Therefore, our study demonstrated that as inhibitor of the "NLRP3 inflammasome-NETs" inflammatory loop, exogenous rMFG-E8 improves angiogenesis and accelerates wound healing, highlighting possible therapeutic potential for DFUs.Gold nanoparticles (Au-NPs) have attracted attention as a promising sensitizer owing to their high atomic number (Z), and because they are considered fully multifunctional, they are preferred over other metal nanoparticles. Cold atmospheric plasma (CAP) has also recently gained attention, especially for cancer treatment, by inducing apoptosis through the formation of reactive oxygen species (ROS). In this study, the activity of different sized Au-NPs with helium-based CAP (He-CAP) was analyzed, and the underlying mechanism was investigated. Treating cells with only small Au-NPs (2 nm) significantly enhanced He-CAP-induced apoptosis. https://www.selleckchem.com/products/anacetrapib-mk-0859.html In comparison, 40 nm and 100 nm Au-NPs failed to enhance cell death. Mechanistically, the synergistic enhancement was due to 2 nm Au-NPs-induced decrease in intracellular glutathione, which led to the generation of intracellular ROS. He-CAP markedly induced ROS generation in an aqueous medium; however, treatment with He-CAP alone did not induce intracellular ROS formation. In contrast, the combined treatment significantly enhanced the intracellular formation of superoxide (O2• -) and hydroxyl radical (•OH). These findings indicate the potential therapeutic use of Au-NPs in combination with CAP and further clarify the role of Au-NPs in He-CAP-aided therapies.Acute respiratory distress syndrome (ARDS) is a devastating syndrome responsible for significant morbidity and mortality. Diffuse alveolar epithelial cell death, including but not limited to apoptosis and necroptosis, is one of the hallmarks of ARDS. Currently, no detectable markers can reflect this feature of ARDS. Hyperoxia-induced lung injury is a well-established murine model that mimics human ARDS. We found that hyperoxia and its derivative, reactive oxygen species (ROS), upregulate miR-185-5p, but not miR-185-3p, in alveolar cells. This observation is particularly more significant in alveolar type II (ATII) than alveolar type I (ATI) cells. Functionally, miR-185-5p promotes expression and activation of both receptor-interacting kinase I (RIPK1) and receptor-interacting kinase III (RIPK3), leading to phosphorylation of mixed lineage kinase domain-like (MLKL) and necroptosis. MiR-185-5p regulates this process probably via suppressing FADD and caspase-8 which are both necroptosis inhibitors. Furthermore, miR-185-5p also promotes intrinsic apoptosis, reflected by enhancing caspase-3/7 and 9 activity. Importantly, extracellular vesicle (EV)-containing miR-185-5p, but not free miR-185-5p, is detectable and significantly elevated after hyperoxia-induced cell death, both in vitro and in vivo. Collectively, hyperoxia-induced miR-185-5p regulates both necroptosis and apoptosis in ATII cells. The extracellular level of EV-cargo miR-185-5p is elevated in the setting of profound epithelial cell death.Cancer cells hijack autophagy pathway to evade anti-cancer therapeutics. Many molecular signaling pathways associated with drug-resistance converge on autophagy induction. Honokiol (HNK), a natural phenolic compound purified from Magnolia grandiflora, has recently been shown to impede breast tumorigenesis and, in the present study, we investigated whether breast cancer cells evoke autophagy to modulate therapeutic efficacy and functional networks of HNK. Indeed, breast cancer cells exhibit increased autophagosomes-accumulation, MAP1LC3B-II/LC3B-II-conversion, expression of ATG proteins as well as elevated fusion of autophagosomes and lysosomes upon HNK treatment. Breast cancer cells treated with HNK demonstrate significant growth inhibition and apoptotic induction, and these biological processes are blunted by macroautophagy/autophagy. Consequently, inhibiting autophagosome formation, abrogating autophagosome-lysosome fusion or genetic-knockout of BECN1 and ATG7 effectively increase HNK-mediated apoptotic induction and growth inhibition.
    thailandensis. Mice immunized intranasally with individual AuNP-protein-LPS conjugates, showed variable degrees of protection against intranasal Bm infection, while an optimized combination formulation (containing protein antigens OmpW, OpcP, and Hemagglutinin, along with LPS) showed complete protection against lethality in a mouse model of inhalational glanders. Animals immunized with different nano-glycoconjugates showed robust antigen-specific antibody responses. Moreover, serum from animals immunized with the optimized nano-glycoconjugate formulation showed sustained antibody responses with increased serum-mediated inhibition of adherence and opsonophagocytic activity in vitro. This study provides the basis for the rational design and construction of a multicomponent vaccine platform against Bm.Sustained activation of NLRP3 inflammasome and release of neutrophil extracellular traps (NETs) impair wound healing of diabetic foot ulcers (DFUs). Our previous study reported that milk fat globule epidermal growth factor VIII (MFG-E8) attenuates tissue damage in systemic lupus erythematosus. However, the functional effect of MFG-E8 on "NLRP3 inflammasome-NETs" inflammatory loop in wound healing of diabetes is not completely elucidated. In this study, neutrophils from DFU patients are susceptible to undergo NETosis, releasing more NETs. The circulating levels of NET components neutrophil elastase and proteinase 3 and inflammatory cytokines IL-1β and IL-18 were significantly elevated in DFU patients compared with healthy controls or diabetic patients, in spite of higher levels of MFG-E8 in DFU patients. In Mfge8 -/- diabetic mice, skin wound displayed exaggerated inflammatory response, including leukocyte infiltration, excessive activation of NLRP3 inflammasome (release of higher IL-1β, IL-18, and TNF-α), largely lodged NETs, resulting in poor angiogenesis and wound closure. When stimulated with high-dose glucose or IL-18, MFG-E8-deficient neutrophils release more NETs than WT neutrophils. After administration of recombinant MFG-E8, IL-18-primed NETosis of WT or Mfge8 -/- neutrophils was significantly inhibited. Furthermore, NET and mCRAMP (component of NETs, the murine equivalent of cathelicidin LL-37 in human)-mediated activation of NLRP3 inflammasome and production of IL-1β/IL-18 were significantly elevated in Mfge8 -/- macrophages compared with WT macrophages, which were also significantly dampened by the administration of rmMFG-E8. Therefore, our study demonstrated that as inhibitor of the "NLRP3 inflammasome-NETs" inflammatory loop, exogenous rMFG-E8 improves angiogenesis and accelerates wound healing, highlighting possible therapeutic potential for DFUs.Gold nanoparticles (Au-NPs) have attracted attention as a promising sensitizer owing to their high atomic number (Z), and because they are considered fully multifunctional, they are preferred over other metal nanoparticles. Cold atmospheric plasma (CAP) has also recently gained attention, especially for cancer treatment, by inducing apoptosis through the formation of reactive oxygen species (ROS). In this study, the activity of different sized Au-NPs with helium-based CAP (He-CAP) was analyzed, and the underlying mechanism was investigated. Treating cells with only small Au-NPs (2 nm) significantly enhanced He-CAP-induced apoptosis. https://www.selleckchem.com/products/anacetrapib-mk-0859.html In comparison, 40 nm and 100 nm Au-NPs failed to enhance cell death. Mechanistically, the synergistic enhancement was due to 2 nm Au-NPs-induced decrease in intracellular glutathione, which led to the generation of intracellular ROS. He-CAP markedly induced ROS generation in an aqueous medium; however, treatment with He-CAP alone did not induce intracellular ROS formation. In contrast, the combined treatment significantly enhanced the intracellular formation of superoxide (O2• -) and hydroxyl radical (•OH). These findings indicate the potential therapeutic use of Au-NPs in combination with CAP and further clarify the role of Au-NPs in He-CAP-aided therapies.Acute respiratory distress syndrome (ARDS) is a devastating syndrome responsible for significant morbidity and mortality. Diffuse alveolar epithelial cell death, including but not limited to apoptosis and necroptosis, is one of the hallmarks of ARDS. Currently, no detectable markers can reflect this feature of ARDS. Hyperoxia-induced lung injury is a well-established murine model that mimics human ARDS. We found that hyperoxia and its derivative, reactive oxygen species (ROS), upregulate miR-185-5p, but not miR-185-3p, in alveolar cells. This observation is particularly more significant in alveolar type II (ATII) than alveolar type I (ATI) cells. Functionally, miR-185-5p promotes expression and activation of both receptor-interacting kinase I (RIPK1) and receptor-interacting kinase III (RIPK3), leading to phosphorylation of mixed lineage kinase domain-like (MLKL) and necroptosis. MiR-185-5p regulates this process probably via suppressing FADD and caspase-8 which are both necroptosis inhibitors. Furthermore, miR-185-5p also promotes intrinsic apoptosis, reflected by enhancing caspase-3/7 and 9 activity. Importantly, extracellular vesicle (EV)-containing miR-185-5p, but not free miR-185-5p, is detectable and significantly elevated after hyperoxia-induced cell death, both in vitro and in vivo. Collectively, hyperoxia-induced miR-185-5p regulates both necroptosis and apoptosis in ATII cells. The extracellular level of EV-cargo miR-185-5p is elevated in the setting of profound epithelial cell death.Cancer cells hijack autophagy pathway to evade anti-cancer therapeutics. Many molecular signaling pathways associated with drug-resistance converge on autophagy induction. Honokiol (HNK), a natural phenolic compound purified from Magnolia grandiflora, has recently been shown to impede breast tumorigenesis and, in the present study, we investigated whether breast cancer cells evoke autophagy to modulate therapeutic efficacy and functional networks of HNK. Indeed, breast cancer cells exhibit increased autophagosomes-accumulation, MAP1LC3B-II/LC3B-II-conversion, expression of ATG proteins as well as elevated fusion of autophagosomes and lysosomes upon HNK treatment. Breast cancer cells treated with HNK demonstrate significant growth inhibition and apoptotic induction, and these biological processes are blunted by macroautophagy/autophagy. Consequently, inhibiting autophagosome formation, abrogating autophagosome-lysosome fusion or genetic-knockout of BECN1 and ATG7 effectively increase HNK-mediated apoptotic induction and growth inhibition.
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  • © 2020 The Authors. STEM CELLS TRANSLATIONAL MEDICINE published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.Intercellular communication orchestrates effective immune responses against disease-causing agents. Extracellular vesicles (EVs) are potent mediators of cell-cell communication. EVs carry bioactive molecules, including microRNAs, which modulate gene expression and function in the recipient cell. Here, we show that formation of cognate primary T-B lymphocyte immune contacts promotes transfer of a very restricted set of T-cell EV-microRNAs (mmu-miR20-a-5p, mmu-miR-25-3p, and mmu-miR-155-3p) to the B cell. Transferred EV-microRNAs target key genes that control B-cell function, including pro-apoptotic BIM and the cell cycle regulator PTEN. EV-microRNAs transferred during T-B cognate interactions also promote survival, proliferation, and antibody class switching. Using mouse chimeras with Rab27KO EV-deficient T cells, we demonstrate that the transfer of small EVs is required for germinal center reaction and antibody production in vivo, revealing a mechanism that controls B-cell responses via the transfer of EV-microRNAs of T-cell origin. These findings also provide mechanistic insight into the Griscelli syndrome, associated with a mutation in the Rab27a gene, and might explain antibody defects observed in this pathogenesis and other immune-related and inflammatory disorders. © 2020 The Authors. Published under the terms of the CC BY 4.0 license.The HoBi-like pestivirus (HoBiPeV), currently classified as Pestivirus H species, is a pathogen associated with a broad spectrum of clinical manifestations in ruminants, particularly in cattle. Since HoBiPeV complete genome sequencing data is scarce, in the present study we described five nearly complete new Brazilian HoBiPeV genomes and further perform a more complete genetic and evolutionary characterization with all additional genome sequences available in the GenBank database. Entropy and selection pressure analysis showed the E2 gene, a surface glycoprotein, is the most variable gene, which also displays the greatest number of sites under positive selection. Phylogenetic and Bayesian inference based on complete genome and Npro gene, respectively, from all HoBiPeV sequences available so far, confirms the existence of three main clades (a, b, and c). The abovementioned analysis suggests that this pestivirus species probably emerged in Asia and spread to different regions including Brazil, where only strains belonging to specific genetic group 'a' have been found. The hypothesis of the HoBiPeV introduction in Brazil (between 1,890 and 1,962), formulated based on Bayesian inference, coincides with a period of intensive importation of water buffalo (Bubalus arnee) and indicine cattle (Bos taurus indicus) from Asia to Brazil, suggesting that this could be the origin of the current Brazilian HoBiPeV genetic group 'a'. © 2020 Blackwell Verlag GmbH.Mitochondrial DNA (mtDNA) encodes a subset of the genes which are responsible for oxidative phosphorylation. Pathogenic mutations in the human mtDNA are often heteroplasmic, where wild-type mtDNA species co-exist with the pathogenic mtDNA and a bioenergetic defect is only seen when the pathogenic mtDNA percentage surpasses a threshold for biochemical manifestations. mtDNA segregation during germline development can explain some of the extreme variation in heteroplasmy from one generation to the next. Patients with high heteroplasmy for deleterious mtDNA species will likely suffer from bona-fide mitochondrial diseases, which currently have no cure. Shifting mtDNA heteroplasmy toward the wild-type mtDNA species could provide a therapeutic option to patients. Mitochondrially targeted engineered nucleases, such as mitoTALENs and mitoZFNs, have been used in vitro in human cells harboring pathogenic patient-derived mtDNA mutations and more recently in vivo in a mouse model of a pathogenic mtDNA point mutation. These gene therapy tools for shifting mtDNA heteroplasmy can also be used in conjunction with other therapies aimed at eliminating and/or preventing the transfer of pathogenic mtDNA from mother to child. © 2020 The Authors.Our previous work indicated exposure of Human liver cell 7702 (HL7702) cells to Microcystin-leucine-arginine (**-LR) for 24 hours can disrupt insulin (INS) signaling by the hyperphosphorylation of specific proteins. https://www.selleckchem.com/products/Tretinoin(Aberela).html For further exploring the time-dependent effect posed by **-LR on this pathway, in the current study, HL7702 cells together with **** were exposed to the **-LR with different concentrations under short-term treatment, and then, protein phosphatase 2A (PP2A) activity and expression of proteins related to INS signaling, as well as the characteristics of their action in the liver, were investigated. The results indicated, in HL7702 cells with 0.5, 1, and 6 hours of treatment by **-LR, PP2A activity showed an obvious decrease in a time and concentration-dependent manner. While the total protein level of Akt, glycogen synthase kinase 3 (GSK-3), and glycogen synthase remained unchanged, GSK-3 and Akt phosphorylation increased significantly. In livers of **** with 1 hour of intraperitoneal injection with **-LR, a similar change in these proteins was observed. In addition, the levels of total IRS1 and p-IRS1 at serine sites showed decreasing and increasing trends,respectively, and the hematoxylin and eosin staining showed that liver tissues of **** in the maximum-dose group exhibited obvious hepatocyte degeneration and hemorrhage. Our results further proved that short-term treatment with **-LR can inhibit PP2A activity and disrupt INS signaling proteins' phosphorylation level, thereby interfering with the INS pathway. Our findings provide a helpful understanding of the toxic effects posed by **-LR on the glucose metabolism of liver via interference with the INS signaling pathway. © 2020 Wiley Periodicals, Inc.BACKGROUND AND AIMS Fractional lasers have become increasingly popular for treating atrophic scars, but their effectiveness is limited for deeper scars. We developed a novel technique (manual fractional thermal contraction technology, MFTCT) using an ultra-pulse CO2 laser and evaluated its efficacy and safety for treating atrophic facial scars. METHODS A total of 44 patients with atrophic facial scars were treated with MFTCT every 8 weeks for 1-4 times. Overall scar improvement was assessed by photographs taken at baseline and 3 months after the last treatment according to the 4-point global assessment scale (GAS) and ECCA grading scale. Improvements in color, distortion, and texture were assessed by the modified Manchester Scar Scale and scored individually from 1 to 4. Pain degrees and adverse reactions during and after treatment were recorded. RESULTS A total of 44 patients completed the treatment and follow-ups; of them, 89% reported at least 50% overall improvement after the last treatment. The mean ECCA scores fell from 67.
    © 2020 The Authors. STEM CELLS TRANSLATIONAL MEDICINE published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.Intercellular communication orchestrates effective immune responses against disease-causing agents. Extracellular vesicles (EVs) are potent mediators of cell-cell communication. EVs carry bioactive molecules, including microRNAs, which modulate gene expression and function in the recipient cell. Here, we show that formation of cognate primary T-B lymphocyte immune contacts promotes transfer of a very restricted set of T-cell EV-microRNAs (mmu-miR20-a-5p, mmu-miR-25-3p, and mmu-miR-155-3p) to the B cell. Transferred EV-microRNAs target key genes that control B-cell function, including pro-apoptotic BIM and the cell cycle regulator PTEN. EV-microRNAs transferred during T-B cognate interactions also promote survival, proliferation, and antibody class switching. Using mouse chimeras with Rab27KO EV-deficient T cells, we demonstrate that the transfer of small EVs is required for germinal center reaction and antibody production in vivo, revealing a mechanism that controls B-cell responses via the transfer of EV-microRNAs of T-cell origin. These findings also provide mechanistic insight into the Griscelli syndrome, associated with a mutation in the Rab27a gene, and might explain antibody defects observed in this pathogenesis and other immune-related and inflammatory disorders. © 2020 The Authors. Published under the terms of the CC BY 4.0 license.The HoBi-like pestivirus (HoBiPeV), currently classified as Pestivirus H species, is a pathogen associated with a broad spectrum of clinical manifestations in ruminants, particularly in cattle. Since HoBiPeV complete genome sequencing data is scarce, in the present study we described five nearly complete new Brazilian HoBiPeV genomes and further perform a more complete genetic and evolutionary characterization with all additional genome sequences available in the GenBank database. Entropy and selection pressure analysis showed the E2 gene, a surface glycoprotein, is the most variable gene, which also displays the greatest number of sites under positive selection. Phylogenetic and Bayesian inference based on complete genome and Npro gene, respectively, from all HoBiPeV sequences available so far, confirms the existence of three main clades (a, b, and c). The abovementioned analysis suggests that this pestivirus species probably emerged in Asia and spread to different regions including Brazil, where only strains belonging to specific genetic group 'a' have been found. The hypothesis of the HoBiPeV introduction in Brazil (between 1,890 and 1,962), formulated based on Bayesian inference, coincides with a period of intensive importation of water buffalo (Bubalus arnee) and indicine cattle (Bos taurus indicus) from Asia to Brazil, suggesting that this could be the origin of the current Brazilian HoBiPeV genetic group 'a'. © 2020 Blackwell Verlag GmbH.Mitochondrial DNA (mtDNA) encodes a subset of the genes which are responsible for oxidative phosphorylation. Pathogenic mutations in the human mtDNA are often heteroplasmic, where wild-type mtDNA species co-exist with the pathogenic mtDNA and a bioenergetic defect is only seen when the pathogenic mtDNA percentage surpasses a threshold for biochemical manifestations. mtDNA segregation during germline development can explain some of the extreme variation in heteroplasmy from one generation to the next. Patients with high heteroplasmy for deleterious mtDNA species will likely suffer from bona-fide mitochondrial diseases, which currently have no cure. Shifting mtDNA heteroplasmy toward the wild-type mtDNA species could provide a therapeutic option to patients. Mitochondrially targeted engineered nucleases, such as mitoTALENs and mitoZFNs, have been used in vitro in human cells harboring pathogenic patient-derived mtDNA mutations and more recently in vivo in a mouse model of a pathogenic mtDNA point mutation. These gene therapy tools for shifting mtDNA heteroplasmy can also be used in conjunction with other therapies aimed at eliminating and/or preventing the transfer of pathogenic mtDNA from mother to child. © 2020 The Authors.Our previous work indicated exposure of Human liver cell 7702 (HL7702) cells to Microcystin-leucine-arginine (MC-LR) for 24 hours can disrupt insulin (INS) signaling by the hyperphosphorylation of specific proteins. https://www.selleckchem.com/products/Tretinoin(Aberela).html For further exploring the time-dependent effect posed by MC-LR on this pathway, in the current study, HL7702 cells together with mice were exposed to the MC-LR with different concentrations under short-term treatment, and then, protein phosphatase 2A (PP2A) activity and expression of proteins related to INS signaling, as well as the characteristics of their action in the liver, were investigated. The results indicated, in HL7702 cells with 0.5, 1, and 6 hours of treatment by MC-LR, PP2A activity showed an obvious decrease in a time and concentration-dependent manner. While the total protein level of Akt, glycogen synthase kinase 3 (GSK-3), and glycogen synthase remained unchanged, GSK-3 and Akt phosphorylation increased significantly. In livers of mice with 1 hour of intraperitoneal injection with MC-LR, a similar change in these proteins was observed. In addition, the levels of total IRS1 and p-IRS1 at serine sites showed decreasing and increasing trends,respectively, and the hematoxylin and eosin staining showed that liver tissues of mice in the maximum-dose group exhibited obvious hepatocyte degeneration and hemorrhage. Our results further proved that short-term treatment with MC-LR can inhibit PP2A activity and disrupt INS signaling proteins' phosphorylation level, thereby interfering with the INS pathway. Our findings provide a helpful understanding of the toxic effects posed by MC-LR on the glucose metabolism of liver via interference with the INS signaling pathway. © 2020 Wiley Periodicals, Inc.BACKGROUND AND AIMS Fractional lasers have become increasingly popular for treating atrophic scars, but their effectiveness is limited for deeper scars. We developed a novel technique (manual fractional thermal contraction technology, MFTCT) using an ultra-pulse CO2 laser and evaluated its efficacy and safety for treating atrophic facial scars. METHODS A total of 44 patients with atrophic facial scars were treated with MFTCT every 8 weeks for 1-4 times. Overall scar improvement was assessed by photographs taken at baseline and 3 months after the last treatment according to the 4-point global assessment scale (GAS) and ECCA grading scale. Improvements in color, distortion, and texture were assessed by the modified Manchester Scar Scale and scored individually from 1 to 4. Pain degrees and adverse reactions during and after treatment were recorded. RESULTS A total of 44 patients completed the treatment and follow-ups; of them, 89% reported at least 50% overall improvement after the last treatment. The mean ECCA scores fell from 67.
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  • A supplementation of vitamin C and Zn may be beneficial in PTB treatment. Previous meta-analysis of randomized controlled trials (RCTs) reported a null effect of Zn supplementation on PTB treatment. The effect of vitamin C supplementation should be investigated by RCTs.Staphylococcus aureus is a common human pathogen that is particularly often associated with antibiotic resistance. The eradication of this ubiquitous infectious agent from its ecological niches and contaminated surfaces is especially complicated by excessive biofilm formation and persisting cells, which evade the antibacterial activity of conventional antibiotics. Here, we present an alternative view of the problem of specific S. aureus eradication. The constitutive heterologous production of highly specific bacteriolytic protease lysostaphin in yeast Pichia pastoris provides an efficient biocontrol agent, specifically killing S. aureus in coculture. A yeast-based anti-S. aureus probiotic was efficient in a high range of temperatures and target-to-effector ratios, indicating its robustness and versatility in eliminating S. aureus cells. The efficient eradication of S. aureus by live lysostaphin-producing P. pastoris was achieved at high scales, providing a simple, biocompatible and cost-effective strategy for S. aureus lysis in bioproduction and surface decontamination. Future biomedical applications based on designer yeast biocontrol agents require evaluation in in vivo models. However, we believe that this strategy is very promising since it provides highly safe, efficient and selective genetically programmed probiotics and targeted biocontrol agents.Muscle cell plasma membrane is frequently damaged by mechanical activity, and its repair requires the membrane protein dysferlin. We previously identified that, similar to dysferlin deficit, lack of annexin A2 (AnxA2) also impairs repair of skeletal myofibers. Here, we have studied the mechanism of AnxA2-mediated muscle cell membrane repair in cultured muscle cells. We find that injury-triggered increase in cytosolic calcium causes AnxA2 to bind dysferlin and accumulate on dysferlin-containing vesicles as well as with dysferlin at the site of membrane injury. AnxA2 accumulates on the injured plasma membrane in cholesterol-rich lipid microdomains and requires Src kinase activity and the presence of cholesterol. Lack of AnxA2 and its failure to translocate to the plasma membrane, both prevent calcium-triggered dysferlin translocation to the plasma membrane and compromise repair of the injured plasma membrane. Our studies identify that Anx2 senses calcium increase and injury-triggered change in plasma membrane cholesterol to facilitate dysferlin delivery and repair of the injured plasma membrane.Barcode medication administration (BCMA) is advocated as a technology that reduces medication errors relating to incorrect patient identity, drug or dose. Little is known, however, about the impact it has on nursing workflow. Our aim was to investigate the impact of BCMA on nursing activity and workflow. A comparative study was conducted on two similar surgical wards within an acute UK hospital. We observed nurses during drug rounds on a non-BCMA ward and a BCMA ward. Data were collected on drug round duration, timeliness of medication administration, patient identification, medication verification and general workflow patterns. BCMA appears not to alter drug round duration, although it may reduce the administration time per dose. Workflow was more streamlined, with less use of the medicines room. The rate of patient identification increased from 74% (of 47) patients to 100% (of 43), with 95% of 255 scannable medication doses verified using the system. This study suggests that BCMA does not affect drug round duration; further research is required to determine the impact it has on timeliness of medication administration. There was reduced variability in the medication administration workflow of nurses, along with an increased patient identification rate and high medication scan rate, representing potential benefits to patient safety.Several epidemiological studies found an association between acute exposure to fine particulate matter of less than 2.5 μm and 10 μm in aerodynamic diameter (PM2.5 and PM10) and cardiovascular diseases, ventricular fibrillation incidence and mortality. The effects of pollution on atrial fibrillation (AF) beyond the first several hours of exposure remain controversial. A total of 145 patients with implantable cardioverter-defibrillators (ICDs), cardiac resynchronization therapy defibrillators (ICD-CRT), or pacemakers were enrolled in this multicentric prospective study. Daily levels of PM2.5 and PM10 were collected from monitoring stations within 20 km of the patient's residence. A Firth Logistic Regression model was used to evaluate the association between AF and daily exposure to PM2.5 and PM10. Exposure levels to PM2.5 and PM10 were moderate, being above the World Health Organization (WHO) PM2.5 and PM10 thresholds of 25 μg/m3 and 50 μg/m3, respectively, on 26% and 18% of the follow-up days. An association was found between daily levels of PM2.5 and PM10 and AF (95% confidence intervals (CIs) of 1.34-2.40 and 1.44-4.28, respectively) for an increase of 50 µg/m3 above the WHO threshold. Daily exposure to moderate PM2.5 and PM10 levels is associated with AF in patients who are not prone to AF.
    We assessed the association between the use of metformin and other antihyperglycemic medications on overall survival in diabetic patients with pancreatic cancer.

    Patients with pancreatic cancer and diabetes between 2000 and 2015 were identified from the Lithuanian Cancer Registry and the National Health Insurance Fund database. Cohort members were classified into six groups according to type 2 diabetes mellitus treatment sulfonylurea monotherapy; metformin monotherapy; insulin monotherapy; metformin and sulfonylurea combination; metformin and other antihyperglycemic medications; all other combinations of oral antihyperglycemic medications. Survival was calculated from the date of cancer diagnosis to the date of death or the end of follow-up (31 December 2018).

    Study group included 454 diabetic patients with pancreatic cancer. We found no statistically significant differences in overall survival between patients by glucose-lowering therapy. https://www.selleckchem.com/products/ots514.html However, highest mortality risk was observed in patients on insulin monotherapy, and better survival was observed in the groups of patients using antihyperglycemic medication combinations, metformin alone, and metformin in combination with sulfonylurea.
    A supplementation of vitamin C and Zn may be beneficial in PTB treatment. Previous meta-analysis of randomized controlled trials (RCTs) reported a null effect of Zn supplementation on PTB treatment. The effect of vitamin C supplementation should be investigated by RCTs.Staphylococcus aureus is a common human pathogen that is particularly often associated with antibiotic resistance. The eradication of this ubiquitous infectious agent from its ecological niches and contaminated surfaces is especially complicated by excessive biofilm formation and persisting cells, which evade the antibacterial activity of conventional antibiotics. Here, we present an alternative view of the problem of specific S. aureus eradication. The constitutive heterologous production of highly specific bacteriolytic protease lysostaphin in yeast Pichia pastoris provides an efficient biocontrol agent, specifically killing S. aureus in coculture. A yeast-based anti-S. aureus probiotic was efficient in a high range of temperatures and target-to-effector ratios, indicating its robustness and versatility in eliminating S. aureus cells. The efficient eradication of S. aureus by live lysostaphin-producing P. pastoris was achieved at high scales, providing a simple, biocompatible and cost-effective strategy for S. aureus lysis in bioproduction and surface decontamination. Future biomedical applications based on designer yeast biocontrol agents require evaluation in in vivo models. However, we believe that this strategy is very promising since it provides highly safe, efficient and selective genetically programmed probiotics and targeted biocontrol agents.Muscle cell plasma membrane is frequently damaged by mechanical activity, and its repair requires the membrane protein dysferlin. We previously identified that, similar to dysferlin deficit, lack of annexin A2 (AnxA2) also impairs repair of skeletal myofibers. Here, we have studied the mechanism of AnxA2-mediated muscle cell membrane repair in cultured muscle cells. We find that injury-triggered increase in cytosolic calcium causes AnxA2 to bind dysferlin and accumulate on dysferlin-containing vesicles as well as with dysferlin at the site of membrane injury. AnxA2 accumulates on the injured plasma membrane in cholesterol-rich lipid microdomains and requires Src kinase activity and the presence of cholesterol. Lack of AnxA2 and its failure to translocate to the plasma membrane, both prevent calcium-triggered dysferlin translocation to the plasma membrane and compromise repair of the injured plasma membrane. Our studies identify that Anx2 senses calcium increase and injury-triggered change in plasma membrane cholesterol to facilitate dysferlin delivery and repair of the injured plasma membrane.Barcode medication administration (BCMA) is advocated as a technology that reduces medication errors relating to incorrect patient identity, drug or dose. Little is known, however, about the impact it has on nursing workflow. Our aim was to investigate the impact of BCMA on nursing activity and workflow. A comparative study was conducted on two similar surgical wards within an acute UK hospital. We observed nurses during drug rounds on a non-BCMA ward and a BCMA ward. Data were collected on drug round duration, timeliness of medication administration, patient identification, medication verification and general workflow patterns. BCMA appears not to alter drug round duration, although it may reduce the administration time per dose. Workflow was more streamlined, with less use of the medicines room. The rate of patient identification increased from 74% (of 47) patients to 100% (of 43), with 95% of 255 scannable medication doses verified using the system. This study suggests that BCMA does not affect drug round duration; further research is required to determine the impact it has on timeliness of medication administration. There was reduced variability in the medication administration workflow of nurses, along with an increased patient identification rate and high medication scan rate, representing potential benefits to patient safety.Several epidemiological studies found an association between acute exposure to fine particulate matter of less than 2.5 μm and 10 μm in aerodynamic diameter (PM2.5 and PM10) and cardiovascular diseases, ventricular fibrillation incidence and mortality. The effects of pollution on atrial fibrillation (AF) beyond the first several hours of exposure remain controversial. A total of 145 patients with implantable cardioverter-defibrillators (ICDs), cardiac resynchronization therapy defibrillators (ICD-CRT), or pacemakers were enrolled in this multicentric prospective study. Daily levels of PM2.5 and PM10 were collected from monitoring stations within 20 km of the patient's residence. A Firth Logistic Regression model was used to evaluate the association between AF and daily exposure to PM2.5 and PM10. Exposure levels to PM2.5 and PM10 were moderate, being above the World Health Organization (WHO) PM2.5 and PM10 thresholds of 25 μg/m3 and 50 μg/m3, respectively, on 26% and 18% of the follow-up days. An association was found between daily levels of PM2.5 and PM10 and AF (95% confidence intervals (CIs) of 1.34-2.40 and 1.44-4.28, respectively) for an increase of 50 µg/m3 above the WHO threshold. Daily exposure to moderate PM2.5 and PM10 levels is associated with AF in patients who are not prone to AF. We assessed the association between the use of metformin and other antihyperglycemic medications on overall survival in diabetic patients with pancreatic cancer. Patients with pancreatic cancer and diabetes between 2000 and 2015 were identified from the Lithuanian Cancer Registry and the National Health Insurance Fund database. Cohort members were classified into six groups according to type 2 diabetes mellitus treatment sulfonylurea monotherapy; metformin monotherapy; insulin monotherapy; metformin and sulfonylurea combination; metformin and other antihyperglycemic medications; all other combinations of oral antihyperglycemic medications. Survival was calculated from the date of cancer diagnosis to the date of death or the end of follow-up (31 December 2018). Study group included 454 diabetic patients with pancreatic cancer. We found no statistically significant differences in overall survival between patients by glucose-lowering therapy. https://www.selleckchem.com/products/ots514.html However, highest mortality risk was observed in patients on insulin monotherapy, and better survival was observed in the groups of patients using antihyperglycemic medication combinations, metformin alone, and metformin in combination with sulfonylurea.
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  • 72%, Deviant Tones = -17.80%, Congruent Words = -28.78%, Incongruent Words = -29.61%) compared to the individual distant channels. Measured vs predicted ERP amplitudes were highly and significantly correlated with control for the N100 (R = 0.5, padj less then 0.05) P300 (R = 0.75, padj less then 0.01), and N400 (R = 0.75, padj less then 0.01) ERPs. CONCLUSION ERP waveforms at distant channels can be combined using a neural network autoencoder to model the control channel features with better precision than those at individual distant channels. This is the first demonstration of feasibility of predicting evoked potentials and brain vital signs using signals recorded from more distant, practical locations. SIGNIFICANCE This solves a key engineering challenge for applications that require portability, comfort, and speed of measurement as design priorities for measurement of event-related potentials across a range of individuals, settings, and circumstances.OBJECTIVE Unipolar intracardiac electrograms (uEGMs) measured inside the atria during electro-anatomic mapping contain diagnostic information about cardiac excitation and tissue properties. The ventricular far field (VFF) caused by ventricular depolarization compromises these signals. Current signal processing techniques require several seconds of local uEGMs to remove the VFF component and thus prolong the clinical mapping procedure. We developed an approach to remove the VFF component using data obtained during initial anatomy acquisition. METHODS We developed two models which can approximate the spatio-temporal distribution of the VFF component based on acquired EGM data Polynomial fit, and dipole fit. Both were benchmarked based on simulated cardiac excitation in two models of the human heart and applied to clinical data. RESULTS VFF data acquired in one atrium were used to estimate model parameters. Under realistic noise conditions, a dipole model approximated the VFF with a median deviation of 0.029mV, yielding a median VFF attenuation of 142. https://www.selleckchem.com/ In a different setup, only VFF data acquired at distances of more than 5mm to the atrial endocardium were used to estimate the model parameters. The VFF component was then extrapolated for a layer of 5mm thickness lining the endocardial tissue. A median deviation of 0.082mV (median VFF attenuation of 49x) was achieved under realistic noise conditions. CONCLUSION It is feasible to model the VFF component in a personalized way and effectively remove it from uEGMs. SIGNIFICANCE Application of our novel, simple and computationally inexpensive methods allows immediate diagnostic assessment of uEGM data without prolonging data acquisition.Multi-wavelength cameras play an essential role in remote photoplethysmography (PPG). Whereas these are readily available for visible light, this is not the case for near infrared (NIR). We propose to modify existing RGB cameras to make them suited for NIR-PPG. In particular, we exploit the spectral leakage of the RGB channels in infrared in combination with a narrow dual-band filter. Such camera modification is simple, cost-effective, easy to implement, and it is shown to attain a pulse rate extraction performance comparable to that of multiple narrow-band NIR cameras.OBJECTIVE A challenging task for an electroencephalography (EEG)-based asynchronous brain-computer interface (BCI) is to effectively distinguish between the idle state and the control state while maintaining a short response time and a high accuracy when commands are issued in the control state. This study proposes a novel hybrid asynchronous BCI system based on a combination of steady-state visual evoked potentials (SSVEPs) in the EEG signal and blink-related electrooculography (EOG) signals. METHODS Twelve buttons corresponding to 12 characters are included in the graphical user interface (GUI). These buttons flicker at different fixed frequencies and phases to evoke SSVEPs and are simultaneously highlighted by changing their sizes. The user can select a character by focusing on its frequency-phase stimulus and simultaneously blinking his/her eyes in accordance with its highlighting as his/her EEG and EOG signals are recorded. A multifrequency band-based canonical correlation analysis (CCA) method is applied to the EEG data to detect the evoked SSVEPs, whereas the EOG data are analyzed to identify the user's blinks. Finally, the target character is identified based on the SSVEP and blink detection results. RESULTS Ten healthy subjects participated in our experiments and achieved an average information transfer rate (ITR) of 105.52 bits/min, an average accuracy of 95.42%, an average response time of 1.34 s and an average false-positive rate (FPR) of 0.8%. CONCLUSION The proposed BCI generates multiple commands with a high ITR and low FPR. SIGNIFICANCE The hybrid asynchronous BCI has great potential for practical applications in communication and control.OBJECTIVES The objective of this study was to report normal echocardiographic values in healthy guinea pigs. ANIMALS, MATERIALS, AND METHODS Twenty-two privately owned, apparently healthy, conscious guinea pigs underwent complete transthoracic echocardiography. Left ventricular (LV), right ventricular, left atrial, and aortic root dimensions were measured, as were forward flow velocities across the mitral, aortic, and pulmonic valves. The effects of age, body weight, sex, and heart rate on these variables were also investigated. RESULTS The median age (interquartile range) was 3.0 (1.8-4.0) years with a body weight of 902 (822-998) grams. Echocardiography was feasible in all conscious animals. Early and late diastolic transmitral flow waves were summated in 17 of 22 individuals. In the remaining five animals, the two waves were reversed (E wave-to-A wave velocity less than 1.0). A positive correlation was detected between body weight and LV internal diameter at end-diastole and end-systole and left atrial diameter (P  less then  0.05). Heart rate was negatively correlated with LV internal diameter at end-systole (r = -0.463, P = 0.035). Age was positively correlated with LV posterior wall thickness at end-diastole and aortic diameter (P  less then  0.05). LV internal diameter at end-systole was larger in males than in females (P = 0.012), while fractional shortening was lower (P = 0.008). CONCLUSIONS Descriptive echocardiography ranges in apparently healthy awake guinea pigs have been provided and can be used for cardiac assessment in these pet animals.
    72%, Deviant Tones = -17.80%, Congruent Words = -28.78%, Incongruent Words = -29.61%) compared to the individual distant channels. Measured vs predicted ERP amplitudes were highly and significantly correlated with control for the N100 (R = 0.5, padj less then 0.05) P300 (R = 0.75, padj less then 0.01), and N400 (R = 0.75, padj less then 0.01) ERPs. CONCLUSION ERP waveforms at distant channels can be combined using a neural network autoencoder to model the control channel features with better precision than those at individual distant channels. This is the first demonstration of feasibility of predicting evoked potentials and brain vital signs using signals recorded from more distant, practical locations. SIGNIFICANCE This solves a key engineering challenge for applications that require portability, comfort, and speed of measurement as design priorities for measurement of event-related potentials across a range of individuals, settings, and circumstances.OBJECTIVE Unipolar intracardiac electrograms (uEGMs) measured inside the atria during electro-anatomic mapping contain diagnostic information about cardiac excitation and tissue properties. The ventricular far field (VFF) caused by ventricular depolarization compromises these signals. Current signal processing techniques require several seconds of local uEGMs to remove the VFF component and thus prolong the clinical mapping procedure. We developed an approach to remove the VFF component using data obtained during initial anatomy acquisition. METHODS We developed two models which can approximate the spatio-temporal distribution of the VFF component based on acquired EGM data Polynomial fit, and dipole fit. Both were benchmarked based on simulated cardiac excitation in two models of the human heart and applied to clinical data. RESULTS VFF data acquired in one atrium were used to estimate model parameters. Under realistic noise conditions, a dipole model approximated the VFF with a median deviation of 0.029mV, yielding a median VFF attenuation of 142. https://www.selleckchem.com/ In a different setup, only VFF data acquired at distances of more than 5mm to the atrial endocardium were used to estimate the model parameters. The VFF component was then extrapolated for a layer of 5mm thickness lining the endocardial tissue. A median deviation of 0.082mV (median VFF attenuation of 49x) was achieved under realistic noise conditions. CONCLUSION It is feasible to model the VFF component in a personalized way and effectively remove it from uEGMs. SIGNIFICANCE Application of our novel, simple and computationally inexpensive methods allows immediate diagnostic assessment of uEGM data without prolonging data acquisition.Multi-wavelength cameras play an essential role in remote photoplethysmography (PPG). Whereas these are readily available for visible light, this is not the case for near infrared (NIR). We propose to modify existing RGB cameras to make them suited for NIR-PPG. In particular, we exploit the spectral leakage of the RGB channels in infrared in combination with a narrow dual-band filter. Such camera modification is simple, cost-effective, easy to implement, and it is shown to attain a pulse rate extraction performance comparable to that of multiple narrow-band NIR cameras.OBJECTIVE A challenging task for an electroencephalography (EEG)-based asynchronous brain-computer interface (BCI) is to effectively distinguish between the idle state and the control state while maintaining a short response time and a high accuracy when commands are issued in the control state. This study proposes a novel hybrid asynchronous BCI system based on a combination of steady-state visual evoked potentials (SSVEPs) in the EEG signal and blink-related electrooculography (EOG) signals. METHODS Twelve buttons corresponding to 12 characters are included in the graphical user interface (GUI). These buttons flicker at different fixed frequencies and phases to evoke SSVEPs and are simultaneously highlighted by changing their sizes. The user can select a character by focusing on its frequency-phase stimulus and simultaneously blinking his/her eyes in accordance with its highlighting as his/her EEG and EOG signals are recorded. A multifrequency band-based canonical correlation analysis (CCA) method is applied to the EEG data to detect the evoked SSVEPs, whereas the EOG data are analyzed to identify the user's blinks. Finally, the target character is identified based on the SSVEP and blink detection results. RESULTS Ten healthy subjects participated in our experiments and achieved an average information transfer rate (ITR) of 105.52 bits/min, an average accuracy of 95.42%, an average response time of 1.34 s and an average false-positive rate (FPR) of 0.8%. CONCLUSION The proposed BCI generates multiple commands with a high ITR and low FPR. SIGNIFICANCE The hybrid asynchronous BCI has great potential for practical applications in communication and control.OBJECTIVES The objective of this study was to report normal echocardiographic values in healthy guinea pigs. ANIMALS, MATERIALS, AND METHODS Twenty-two privately owned, apparently healthy, conscious guinea pigs underwent complete transthoracic echocardiography. Left ventricular (LV), right ventricular, left atrial, and aortic root dimensions were measured, as were forward flow velocities across the mitral, aortic, and pulmonic valves. The effects of age, body weight, sex, and heart rate on these variables were also investigated. RESULTS The median age (interquartile range) was 3.0 (1.8-4.0) years with a body weight of 902 (822-998) grams. Echocardiography was feasible in all conscious animals. Early and late diastolic transmitral flow waves were summated in 17 of 22 individuals. In the remaining five animals, the two waves were reversed (E wave-to-A wave velocity less than 1.0). A positive correlation was detected between body weight and LV internal diameter at end-diastole and end-systole and left atrial diameter (P  less then  0.05). Heart rate was negatively correlated with LV internal diameter at end-systole (r = -0.463, P = 0.035). Age was positively correlated with LV posterior wall thickness at end-diastole and aortic diameter (P  less then  0.05). LV internal diameter at end-systole was larger in males than in females (P = 0.012), while fractional shortening was lower (P = 0.008). CONCLUSIONS Descriptive echocardiography ranges in apparently healthy awake guinea pigs have been provided and can be used for cardiac assessment in these pet animals.
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  • Both soils, the vertical profile distribution of OBT concentration showed no consistent tendency, and there were no significant differences in the HTO and OBT concentrations between different soil layers, except for the highest concentration. Whether uncultivated soil or cultivated soil, HTO activity concentrations showed an apparent spatial distribution and seasonal variability, decreasing with the distance to the release sources and with sampling time, while OBT concentrations showed lower spatial and seasonal variability than HTO. In most cases, the OBT/HTO ratios were less than 1, with average values of 1.01 ± 0.48 and 1.06 ± 0.86 for cultivated soil and cultivated soil samples, respectively. The results of this work suggest that farming may affect tritium behavior in soil, while the spatial and temporal distribution of tritium is only slightly impacted.
    The present study analyzed different protocols of administration of boronophenylalanine (BPA) and sodium butyrate (NaB) to increase the **** efficacy for poorly differentiated thyroid cancer (PDTC).

    Nude **** implanted with human PDTC cells (WRO) were distributed into four protocols 1) BPA; 2) BPA+ip NaB; 3) BPA+oral NaB; 4) Control. Biodistribution and histologic studies were performed. LAT (BPA transporter) isoforms gene expression was assessed by RT-PCR.

    Tumor growth delay was observed in animals of the Protocol #3 (p<0.05). NaB (Protocol #2) increased tumor boron uptake 2-h post BPA injection (p < 0.05). On the other hand, NaB upregulated the expression of all the isoforms of the LAT transporter in vitro. Histologic studies showed a significant decrease of mitotic activity and an increase of vacuoles in tumors of Protocol #3. Neutrons alone or combined with NaB caused some tumor growth delay (p<0.05), while in the **** and ****+NaB groups, there was a halt in tumor growth in 70 and 80% of the animals, respectively.

    Intraperitoneally administration of NaB increased boron uptake while oral administration for a longer period of time induced tumor growth delay previous to BPA administration. The use of NaB via ip would optimize the irradiation results.
    Intraperitoneally administration of NaB increased boron uptake while oral administration for a longer period of time induced tumor growth delay previous to BPA administration. The use of NaB via ip would optimize the irradiation results.Behavioral learning is driven by adaptive changes in the activation of behaviorally relevant neuronal ensembles. https://www.selleckchem.com/products/otx015.html This learning-specific reorganization of neuronal circuits is correlated with activity-dependent modifications of synaptic dynamics. However, a definitive causal link remains to be established. How is synaptic plasticity distributed among circuits to eventually shape behavioral learning? A multi-scale understanding of the progressive plasticity is hindered by the lack of techniques for monitoring and manipulating these events. The current rise of synaptic optogenetics, especially combined with brain-wide circuit imaging, opens an entirely new avenue for studying causality at multiple scales. In this review, we summarize these technical achievements and discuss challenges in linking the plasticity across levels to elucidate the multi-scale mechanisms of learning.Honey and its phenolic compounds specifically chrysin are focused as nutritional supplements and likewise as valued phytochemicals, nutraceuticals, and phytopharmaceuticals alone, or adjuvant with some conventional medications to cause synergistic therapeutic or cytotoxic effects. Through the verified beneficial strategies combat several disturbances, phenolic compounds play fundamental functions in the avoidance and treatment of disorders. Oxidative stress, inflammation, and apoptosis are the three most imperative physiological reactions in the prevalence of numerous ailments. Honey, chrysin, and other phenolic compounds detected in honey can modify clinical conditions via modulation of these contrivances and correlated signaling pathways. The current study desires to review the therapeutic effects of honey and its allied molecular mechanisms. Evidenced-base studies show that honey would represent therapeutic potential against various types of cancer and tumor proliferation (colorectal cancer, breast cancer, bladder cancer, leukemia, glioma, hepatocellular cancer, pancreatic cancer, and melanoma), wounds, diabetes mellitus, neurological (depression, Parkinson disease, and Alzheimer's disease), respiratory, gastrointestinal (peptic ulcer and ulcerative colitis), cardiovascular disorders, renal injuries, liver diseases and many other kinds of physiological dysfunctionalities through various molecular mechanisms contributed with oxidative stress, inflammatory process, and apoptosis.Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor impairments. Most PD drugs act by improving motor impairments, whereas very few drugs that efficiently recover PD-related neuropathological features, particularly α-synuclein-related toxicity, have been developed. In this study, we found that papaverine (PAP) attenuated behavioral deficits and protected against nigrostriatal dopaminergic degeneration in the subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid (MPTP/P) mouse model of PD. Histological analysis of tissue dissected from **** sacrificed nearly 3 weeks after the completion of treatment revealed that PAP significantly ameliorated microglia/astrocyte activation in the striatum and substantia nigra of MPTP/P-treated ****. In addition, PAP diminished α-synuclein expression and aggregation in this model. Furthermore, PAP inhibited the phosphorylation of α-synuclein at serine 129, which may underlie the observed reduction in α-synuclein aggregation. PAP also reduced the expression of matrix metalloproteinase-3 (MMP-3), and the MMP3-positive area co-labeled with thioflavin-S. Taken together, our data suggest that PAP inhibits dopaminergic neuronal cell death and α-synuclein aggregation by suppressing neuroinflammation and MMP-3 expression in the subacute MPTP/P mouse model of PD. Accordingly, PAP may be a promising drug for the treatment of PD.
    Both soils, the vertical profile distribution of OBT concentration showed no consistent tendency, and there were no significant differences in the HTO and OBT concentrations between different soil layers, except for the highest concentration. Whether uncultivated soil or cultivated soil, HTO activity concentrations showed an apparent spatial distribution and seasonal variability, decreasing with the distance to the release sources and with sampling time, while OBT concentrations showed lower spatial and seasonal variability than HTO. In most cases, the OBT/HTO ratios were less than 1, with average values of 1.01 ± 0.48 and 1.06 ± 0.86 for cultivated soil and cultivated soil samples, respectively. The results of this work suggest that farming may affect tritium behavior in soil, while the spatial and temporal distribution of tritium is only slightly impacted. The present study analyzed different protocols of administration of boronophenylalanine (BPA) and sodium butyrate (NaB) to increase the BNCT efficacy for poorly differentiated thyroid cancer (PDTC). Nude mice implanted with human PDTC cells (WRO) were distributed into four protocols 1) BPA; 2) BPA+ip NaB; 3) BPA+oral NaB; 4) Control. Biodistribution and histologic studies were performed. LAT (BPA transporter) isoforms gene expression was assessed by RT-PCR. Tumor growth delay was observed in animals of the Protocol #3 (p<0.05). NaB (Protocol #2) increased tumor boron uptake 2-h post BPA injection (p < 0.05). On the other hand, NaB upregulated the expression of all the isoforms of the LAT transporter in vitro. Histologic studies showed a significant decrease of mitotic activity and an increase of vacuoles in tumors of Protocol #3. Neutrons alone or combined with NaB caused some tumor growth delay (p<0.05), while in the BNCT and BNCT+NaB groups, there was a halt in tumor growth in 70 and 80% of the animals, respectively. Intraperitoneally administration of NaB increased boron uptake while oral administration for a longer period of time induced tumor growth delay previous to BPA administration. The use of NaB via ip would optimize the irradiation results. Intraperitoneally administration of NaB increased boron uptake while oral administration for a longer period of time induced tumor growth delay previous to BPA administration. The use of NaB via ip would optimize the irradiation results.Behavioral learning is driven by adaptive changes in the activation of behaviorally relevant neuronal ensembles. https://www.selleckchem.com/products/otx015.html This learning-specific reorganization of neuronal circuits is correlated with activity-dependent modifications of synaptic dynamics. However, a definitive causal link remains to be established. How is synaptic plasticity distributed among circuits to eventually shape behavioral learning? A multi-scale understanding of the progressive plasticity is hindered by the lack of techniques for monitoring and manipulating these events. The current rise of synaptic optogenetics, especially combined with brain-wide circuit imaging, opens an entirely new avenue for studying causality at multiple scales. In this review, we summarize these technical achievements and discuss challenges in linking the plasticity across levels to elucidate the multi-scale mechanisms of learning.Honey and its phenolic compounds specifically chrysin are focused as nutritional supplements and likewise as valued phytochemicals, nutraceuticals, and phytopharmaceuticals alone, or adjuvant with some conventional medications to cause synergistic therapeutic or cytotoxic effects. Through the verified beneficial strategies combat several disturbances, phenolic compounds play fundamental functions in the avoidance and treatment of disorders. Oxidative stress, inflammation, and apoptosis are the three most imperative physiological reactions in the prevalence of numerous ailments. Honey, chrysin, and other phenolic compounds detected in honey can modify clinical conditions via modulation of these contrivances and correlated signaling pathways. The current study desires to review the therapeutic effects of honey and its allied molecular mechanisms. Evidenced-base studies show that honey would represent therapeutic potential against various types of cancer and tumor proliferation (colorectal cancer, breast cancer, bladder cancer, leukemia, glioma, hepatocellular cancer, pancreatic cancer, and melanoma), wounds, diabetes mellitus, neurological (depression, Parkinson disease, and Alzheimer's disease), respiratory, gastrointestinal (peptic ulcer and ulcerative colitis), cardiovascular disorders, renal injuries, liver diseases and many other kinds of physiological dysfunctionalities through various molecular mechanisms contributed with oxidative stress, inflammatory process, and apoptosis.Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor impairments. Most PD drugs act by improving motor impairments, whereas very few drugs that efficiently recover PD-related neuropathological features, particularly α-synuclein-related toxicity, have been developed. In this study, we found that papaverine (PAP) attenuated behavioral deficits and protected against nigrostriatal dopaminergic degeneration in the subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid (MPTP/P) mouse model of PD. Histological analysis of tissue dissected from mice sacrificed nearly 3 weeks after the completion of treatment revealed that PAP significantly ameliorated microglia/astrocyte activation in the striatum and substantia nigra of MPTP/P-treated mice. In addition, PAP diminished α-synuclein expression and aggregation in this model. Furthermore, PAP inhibited the phosphorylation of α-synuclein at serine 129, which may underlie the observed reduction in α-synuclein aggregation. PAP also reduced the expression of matrix metalloproteinase-3 (MMP-3), and the MMP3-positive area co-labeled with thioflavin-S. Taken together, our data suggest that PAP inhibits dopaminergic neuronal cell death and α-synuclein aggregation by suppressing neuroinflammation and MMP-3 expression in the subacute MPTP/P mouse model of PD. Accordingly, PAP may be a promising drug for the treatment of PD.
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  • Administering an abbreviated global cognitive test, such as the Montreal Cognitive Assessment (****), is necessary for the recommended first-level diagnostic criteria for mild cognitive impairment (MCI) in Parkinson's disease (PD). Level II requires administering cognitive functioning neuropsychological tests. The ****'s suitability for identifying PD-MCI is questionable and, despite the importance of cognitive deficits reflected through daily functioning in identifying PD-MCI, knowledge about it is scarce.

    To explore neuropsychological test scores of patients with PD who were categorized based on their **** scores and to analyze correlations between this categorization and patients' self-reports about daily functional-related cognitive abilities.

    A total of 78 patients aged 42 to 78 years participated 46 with low **** scores (22-25) and 32 with high **** scores (26-30). Medical assessments and level II neuropsychological assessment tools were administered along with standardized self-report questionnaith PD who are at risk for cognitive decline.
    Patients with Parkinson's disease (PD) present with a broad spectrum of nonmotor features including autonomic disorders. More severe autonomic dysfunction in PD is associated with increased cognitive deficits. The presence of cerebral small-vessel disease, measured by T2-weighted magnetic resonance imaging white matter hyperintensity (WMH) burden, is also observed in patients with PD with faster cognitive decline.

    To investigate whether baseline orthostatic hypotension and autonomic dysfunction in early-stage PD affect later cognitive decline via mediation through cerebral small-vessel disease.

    De novo PD patients (N = 365) and age-matched controls (N = 174) with baseline T2-weighted/ fluid-attenuated inversion recovery scans were selected from the Parkinson's Progression Markers Initiative. WMHs were automatically segmented. Mediation analysis was used to assess whether WMH load mediates the effect of orthostatic hypotension and autonomic dysfunction (measured by Scales for Outcomes in Parkinson's Disec hypotension and partially mediate the effect of autonomic dysregulation on future cognitive decline in patients with PD. Our findings support the hypothesis that autonomic dysfunction in early clinical stages predisposes the brain to WMHs through dysregulation of the blood flow in the small vessels. This in turn increases the risk of future cognitive impairment in early PD.
    People with Parkinson's disease (PD) can develop multidomain cognitive impairments; however, it is unclear whether different pathologies underlie domain-specific cognitive dysfunction.

    We investigated the contribution of vascular copathology severity and location, as measured by MRI white matter hyperintensities (WMHs), to domain-specific cognitive impairment in PD.

    We studied 85 PD (66.6 ± 9.2 years) and 18 control (65.9 ± 6.6) participants. Using the Fazekas scale for rating the severity of WMH, we subdivided PD into 14 PD
    WMH
    and 71 PD
    WMH
    . Participants underwent global, executive, visuospatial, episodic memory, and language testing. We performed nonparametric permutation testing to create WMH probability maps based on PD-WMH group and cognitive test performance.

    The PD
    WMH
    group showed worse global and executive cognitive performance than the PD
    WMH
    group. On individual tests, the PD
    WMH
    group showed worse Montreal Cognitive Assessment (****), Stroop, Symbol Digit Modalities Test (Simity to vascular lesions could contribute to these specific cognitive impairments. https://www.selleckchem.com/products/epacadostat-incb024360.html Early treatment of vascular disease might mitigate some executive dysfunction in a subset of patients with PD.
    Poor medication adherence in chronic illnesses such as Parkinson's disease (PD) is a significant but potentially addressable issue if core components are systematically measured.

    To assess whether rating scales used in PD adequately cover essential components of medication adherence.

    We accessed 5 databases targeting articles published before October 2019 and using rating scales to measure medication adherence in PD. The ABC Taxonomy from the European Ascertaining Barriers to Compliance Consortium and World Health Organization recommendations were used as the evaluation standard of 5 essential adherence dimensions (patient-based, health system-based, social-based, therapy-based, and health condition-based), 3 phases (initiation, implementation, and discontinuation), and 2 factors (intentional and nonintentional).

    We screened 192 and selected 16 studies, collectively using 5 medication adherence rating scales. No scale covered all essential components of medication adherence (dimensions, phases, factors). The Morisky Medication Adherence Scales were the most frequently used (11 studies), but they measure only 2 dimensions and phases. The Stendal Adherence to Medication Score (used in 1 study) measured all phases but only 2 dimensions, and the Brief Medication Questionnaire (used in 3 studies) measured 3 dimensions and 2 phases. Distinctions between intentional and nonintentional factors were not completely considered in any scale.

    Although multiple studies target medication adherence in PD, the used scales did not measure all recommended components, highlighting the need to develop a sensitive, specific, and comprehensive tool for measuring medication adherence among patients with PD.
    Although multiple studies target medication adherence in PD, the used scales did not measure all recommended components, highlighting the need to develop a sensitive, specific, and comprehensive tool for measuring medication adherence among patients with PD.
    Cardiorespiratory impairments are considered the main cause of mortality in the late stages of Parkinson's. Aerobic exercise has been shown to improve pulmonary function in asthmatic patients and in healthy people. However, effects of aerobic exercise on cardiopulmonary function in people with Parkinson's have not been investigated. Therefore, this study aimed to review the effects of aerobic exercise on cardiopulmonary function in people with Parkinson's.

    A systematic search was conducted using MEDLINE, AMED, CINHAL Plus, and relevant associated keywords, from January 1970 to January 2020. Inclusion criteria for the studies were aerobic exercise as part of the intervention, pulmonary function test, and/or cardiopulmonary exercise test as outcome measures.

    In total, 329 citations were identified from the search, of which nine were included in this review. In general, aerobic exercise was found to have positive effects on cardiac function for people with Parkinson's, but there is a lack of studies on the effects of aerobic exercise on pulmonary function.
    Administering an abbreviated global cognitive test, such as the Montreal Cognitive Assessment (MoCA), is necessary for the recommended first-level diagnostic criteria for mild cognitive impairment (MCI) in Parkinson's disease (PD). Level II requires administering cognitive functioning neuropsychological tests. The MoCA's suitability for identifying PD-MCI is questionable and, despite the importance of cognitive deficits reflected through daily functioning in identifying PD-MCI, knowledge about it is scarce. To explore neuropsychological test scores of patients with PD who were categorized based on their MoCA scores and to analyze correlations between this categorization and patients' self-reports about daily functional-related cognitive abilities. A total of 78 patients aged 42 to 78 years participated 46 with low MoCA scores (22-25) and 32 with high MoCA scores (26-30). Medical assessments and level II neuropsychological assessment tools were administered along with standardized self-report questionnaith PD who are at risk for cognitive decline. Patients with Parkinson's disease (PD) present with a broad spectrum of nonmotor features including autonomic disorders. More severe autonomic dysfunction in PD is associated with increased cognitive deficits. The presence of cerebral small-vessel disease, measured by T2-weighted magnetic resonance imaging white matter hyperintensity (WMH) burden, is also observed in patients with PD with faster cognitive decline. To investigate whether baseline orthostatic hypotension and autonomic dysfunction in early-stage PD affect later cognitive decline via mediation through cerebral small-vessel disease. De novo PD patients (N = 365) and age-matched controls (N = 174) with baseline T2-weighted/ fluid-attenuated inversion recovery scans were selected from the Parkinson's Progression Markers Initiative. WMHs were automatically segmented. Mediation analysis was used to assess whether WMH load mediates the effect of orthostatic hypotension and autonomic dysfunction (measured by Scales for Outcomes in Parkinson's Disec hypotension and partially mediate the effect of autonomic dysregulation on future cognitive decline in patients with PD. Our findings support the hypothesis that autonomic dysfunction in early clinical stages predisposes the brain to WMHs through dysregulation of the blood flow in the small vessels. This in turn increases the risk of future cognitive impairment in early PD. People with Parkinson's disease (PD) can develop multidomain cognitive impairments; however, it is unclear whether different pathologies underlie domain-specific cognitive dysfunction. We investigated the contribution of vascular copathology severity and location, as measured by MRI white matter hyperintensities (WMHs), to domain-specific cognitive impairment in PD. We studied 85 PD (66.6 ± 9.2 years) and 18 control (65.9 ± 6.6) participants. Using the Fazekas scale for rating the severity of WMH, we subdivided PD into 14 PD WMH and 71 PD WMH . Participants underwent global, executive, visuospatial, episodic memory, and language testing. We performed nonparametric permutation testing to create WMH probability maps based on PD-WMH group and cognitive test performance. The PD WMH group showed worse global and executive cognitive performance than the PD WMH group. On individual tests, the PD WMH group showed worse Montreal Cognitive Assessment (MoCA), Stroop, Symbol Digit Modalities Test (Simity to vascular lesions could contribute to these specific cognitive impairments. https://www.selleckchem.com/products/epacadostat-incb024360.html Early treatment of vascular disease might mitigate some executive dysfunction in a subset of patients with PD. Poor medication adherence in chronic illnesses such as Parkinson's disease (PD) is a significant but potentially addressable issue if core components are systematically measured. To assess whether rating scales used in PD adequately cover essential components of medication adherence. We accessed 5 databases targeting articles published before October 2019 and using rating scales to measure medication adherence in PD. The ABC Taxonomy from the European Ascertaining Barriers to Compliance Consortium and World Health Organization recommendations were used as the evaluation standard of 5 essential adherence dimensions (patient-based, health system-based, social-based, therapy-based, and health condition-based), 3 phases (initiation, implementation, and discontinuation), and 2 factors (intentional and nonintentional). We screened 192 and selected 16 studies, collectively using 5 medication adherence rating scales. No scale covered all essential components of medication adherence (dimensions, phases, factors). The Morisky Medication Adherence Scales were the most frequently used (11 studies), but they measure only 2 dimensions and phases. The Stendal Adherence to Medication Score (used in 1 study) measured all phases but only 2 dimensions, and the Brief Medication Questionnaire (used in 3 studies) measured 3 dimensions and 2 phases. Distinctions between intentional and nonintentional factors were not completely considered in any scale. Although multiple studies target medication adherence in PD, the used scales did not measure all recommended components, highlighting the need to develop a sensitive, specific, and comprehensive tool for measuring medication adherence among patients with PD. Although multiple studies target medication adherence in PD, the used scales did not measure all recommended components, highlighting the need to develop a sensitive, specific, and comprehensive tool for measuring medication adherence among patients with PD. Cardiorespiratory impairments are considered the main cause of mortality in the late stages of Parkinson's. Aerobic exercise has been shown to improve pulmonary function in asthmatic patients and in healthy people. However, effects of aerobic exercise on cardiopulmonary function in people with Parkinson's have not been investigated. Therefore, this study aimed to review the effects of aerobic exercise on cardiopulmonary function in people with Parkinson's. A systematic search was conducted using MEDLINE, AMED, CINHAL Plus, and relevant associated keywords, from January 1970 to January 2020. Inclusion criteria for the studies were aerobic exercise as part of the intervention, pulmonary function test, and/or cardiopulmonary exercise test as outcome measures. In total, 329 citations were identified from the search, of which nine were included in this review. In general, aerobic exercise was found to have positive effects on cardiac function for people with Parkinson's, but there is a lack of studies on the effects of aerobic exercise on pulmonary function.
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  • ty Press on behalf of the International Epidemiological Association.Although the ability of individuals with end-stage renal disease to maintain body homoeostasis is equally impaired during all weekdays, conventional haemodialysis (HD) treatment is scheduled thrice weekly, containing two short and one long interdialytic interval. This intermittent nature of HD and the consequent fluctuations in volume, metabolic parameters and electrolytes have long been hypothesized to predispose to complications. Large observational studies link the first weekday with an increased risk of cardiovascular morbidity and mortality. Several schemes of frequent and/or longer, home or in-centre HD have been introduced, aiming to alleviate the above risks by both increasing total dialysis duration and reducing the duration of interdialytic intervals. Observational studies in this field have non-uniform results, showing that enhanced frequency in home (but not in-centre) HD is associated with reduced mortality. Evidence from the randomized Daily and Nocturnal Trials of the Frequent HD Network suggest the opposite, showing mortality benefits with in-centre daily but not with home nocturnal dialysis. Secondary analyses of these trials indicate that daily and nocturnal schedules do not have equal effects on intermediate outcomes. Alternative schemes, such as thrice weekly in-centre nocturnal HD or every-other-day HD, seem to also offer improvements in several intermediate endpoints, but need further testing with randomized trials. This review summarizes the effects of frequent and/or longer HD methods on hard and intermediate outcomes, attempting to provide a balanced overview of the field. © The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.MOTIVATION For the diagnosis of cancer, manually counting nuclei on massive histopathological images is tedious and the counting results might vary due to the subjective nature of the operation. RESULTS This paper presents a new segmentation and counting method for nuclei, which can automatically provide nucleus counting results. This method segments nuclei with detected nuclei seed markers through a modified simple one-pass superpixel segmentation method. Rather than using a single pixel as a seed, we created a superseed for each nucleus to involve more information for improved segmentation results. Nucleus pixels are extracted by a newly proposed fusing method to reduce stain variations and preserve nucleus contour information. By evaluating segmentation results, the proposed method was compared to five existing methods on a dataset with 52 immunohistochemically (IHC) stained images. Our proposed method produced the highest mean F1-score of 0.668. By evaluating the counting results, another dataset with more than 30,000 IHC stained nuclei in 88 images were prepared. The correlation between automatically generated nucleus counting results and manual nucleus counting results was up to R2 = 0.901 (p  less then  0.001). By evaluating segmentation results of proposed method-based tool, we tested on a 2018 Data Science Bowl (DSB) competition dataset, three users obtained DSB score of 0.331 ± 0.006. AVAILABILITY The proposed method has been implemented as a plugin tool in ImageJ and the source code can be freely downloaded. SUPPLEMENTARY INFORMATION Supplementary data are available at https//www.dropbox.com/sh/e7oz4nhp3gekvk4/AAC-xuqg5DUx0H5JdqPApbWTa?dl=0s online. © The Author(s) (2020). Published by Oxford University Press. All rights reserved. For Permissions, please email journals.permissions@oup.com.Research on health systems in resource-limited settings has garnered considerable attention, but the dispensing of individual prescriptions has not been thoroughly explored as a specific bottleneck to effective delivery of care. The rise of human immunodeficiency virus/tuberculosis prevalence and non-communicable diseases in the Kingdom of eSwatini has introduced significant pressures on health facilities to meet patient demands for lifelong medications. Because automated pill counting methods are impracticable and expensive, most prescriptions are made by means of manually counting individual prescriptions using a plastic dish and spatula. The aim of this work was to examine the perceptions of health providers of causes for pill counting errors, and pill counting's impact on clinic workflow. Our study took place in 13 randomly selected public health facilities in eSwatini, stratified by three groups based on monthly patient volumes. Thirty-one participants who count pills regularly and 13 clinic supervisors ng the burden of pill counting could lead to improved clinic quality and possibly improve patient outcomes. © The Author(s) 2020. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine. All rights reserved. https://www.selleckchem.com/products/ficz.html For permissions, please e-mail journals.permissions@oup.com.In this article, I provide a phenomenological exploration of the role played by narrativity in shaping affective experience. I start by surveying and identifying different ways in which linguistic and narrative expression contribute to structure and regulate emotions, and I then expand on these insights by taking into consideration the phenomenology of borderline personality disorder. Disruptions of narrative abilities have been shown to be central to the illness, and I argue that these disruptions are at the origin of a number of alterations of affective experience. In particular, I suggest that due to the narrative "fragmentation" characteristic of the disorder, the emotions experienced by borderline patients can be less differentiated and have a predominantly bodily and unregulated character. © The Author(s) 2020. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.BACKGROUND Bouillon cubes are a potential vehicle for iron fortification. They are currently fortified with ferric pyrophosphate (FePP), which is known to be poorly absorbed. The objective of this study was to assess the iron absorption of Aspergillus oryzae grown in FePP (ASP-p) and compare it with FePP and ferrous sulfate (FeSO4)-fortified bouillon cubes. METHODS In 2 single-blinded, crossover studies, healthy women with serum ferritin concentrations less then 40 μg/L were randomly assigned to consume a rice-vegetable meal with iron-fortified chicken bouillon. Subjects in study I (n = 17, 18-26 y) consumed iron from both iron sources as 57FePP and 58ASP-p (intrinsically labeled with 58FePP) with a meal containing 4.2 mg of total iron provided for 3 d. Study II (n = 18, 18-29 y) was similar except that subjects consumed 57FeSO4 and 58ASP-p. Whole-blood stable isotope enrichment after 14 d was used to measure fractional iron absorption. Hemoglobin, hematocrit, serum ferritin, hepcidin, and serum C-reactive protein were analyzed at baseline and at 14 d.
    ty Press on behalf of the International Epidemiological Association.Although the ability of individuals with end-stage renal disease to maintain body homoeostasis is equally impaired during all weekdays, conventional haemodialysis (HD) treatment is scheduled thrice weekly, containing two short and one long interdialytic interval. This intermittent nature of HD and the consequent fluctuations in volume, metabolic parameters and electrolytes have long been hypothesized to predispose to complications. Large observational studies link the first weekday with an increased risk of cardiovascular morbidity and mortality. Several schemes of frequent and/or longer, home or in-centre HD have been introduced, aiming to alleviate the above risks by both increasing total dialysis duration and reducing the duration of interdialytic intervals. Observational studies in this field have non-uniform results, showing that enhanced frequency in home (but not in-centre) HD is associated with reduced mortality. Evidence from the randomized Daily and Nocturnal Trials of the Frequent HD Network suggest the opposite, showing mortality benefits with in-centre daily but not with home nocturnal dialysis. Secondary analyses of these trials indicate that daily and nocturnal schedules do not have equal effects on intermediate outcomes. Alternative schemes, such as thrice weekly in-centre nocturnal HD or every-other-day HD, seem to also offer improvements in several intermediate endpoints, but need further testing with randomized trials. This review summarizes the effects of frequent and/or longer HD methods on hard and intermediate outcomes, attempting to provide a balanced overview of the field. © The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.MOTIVATION For the diagnosis of cancer, manually counting nuclei on massive histopathological images is tedious and the counting results might vary due to the subjective nature of the operation. RESULTS This paper presents a new segmentation and counting method for nuclei, which can automatically provide nucleus counting results. This method segments nuclei with detected nuclei seed markers through a modified simple one-pass superpixel segmentation method. Rather than using a single pixel as a seed, we created a superseed for each nucleus to involve more information for improved segmentation results. Nucleus pixels are extracted by a newly proposed fusing method to reduce stain variations and preserve nucleus contour information. By evaluating segmentation results, the proposed method was compared to five existing methods on a dataset with 52 immunohistochemically (IHC) stained images. Our proposed method produced the highest mean F1-score of 0.668. By evaluating the counting results, another dataset with more than 30,000 IHC stained nuclei in 88 images were prepared. The correlation between automatically generated nucleus counting results and manual nucleus counting results was up to R2 = 0.901 (p  less then  0.001). By evaluating segmentation results of proposed method-based tool, we tested on a 2018 Data Science Bowl (DSB) competition dataset, three users obtained DSB score of 0.331 ± 0.006. AVAILABILITY The proposed method has been implemented as a plugin tool in ImageJ and the source code can be freely downloaded. SUPPLEMENTARY INFORMATION Supplementary data are available at https//www.dropbox.com/sh/e7oz4nhp3gekvk4/AAC-xuqg5DUx0H5JdqPApbWTa?dl=0s online. © The Author(s) (2020). Published by Oxford University Press. All rights reserved. For Permissions, please email journals.permissions@oup.com.Research on health systems in resource-limited settings has garnered considerable attention, but the dispensing of individual prescriptions has not been thoroughly explored as a specific bottleneck to effective delivery of care. The rise of human immunodeficiency virus/tuberculosis prevalence and non-communicable diseases in the Kingdom of eSwatini has introduced significant pressures on health facilities to meet patient demands for lifelong medications. Because automated pill counting methods are impracticable and expensive, most prescriptions are made by means of manually counting individual prescriptions using a plastic dish and spatula. The aim of this work was to examine the perceptions of health providers of causes for pill counting errors, and pill counting's impact on clinic workflow. Our study took place in 13 randomly selected public health facilities in eSwatini, stratified by three groups based on monthly patient volumes. Thirty-one participants who count pills regularly and 13 clinic supervisors ng the burden of pill counting could lead to improved clinic quality and possibly improve patient outcomes. © The Author(s) 2020. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine. All rights reserved. https://www.selleckchem.com/products/ficz.html For permissions, please e-mail journals.permissions@oup.com.In this article, I provide a phenomenological exploration of the role played by narrativity in shaping affective experience. I start by surveying and identifying different ways in which linguistic and narrative expression contribute to structure and regulate emotions, and I then expand on these insights by taking into consideration the phenomenology of borderline personality disorder. Disruptions of narrative abilities have been shown to be central to the illness, and I argue that these disruptions are at the origin of a number of alterations of affective experience. In particular, I suggest that due to the narrative "fragmentation" characteristic of the disorder, the emotions experienced by borderline patients can be less differentiated and have a predominantly bodily and unregulated character. © The Author(s) 2020. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.BACKGROUND Bouillon cubes are a potential vehicle for iron fortification. They are currently fortified with ferric pyrophosphate (FePP), which is known to be poorly absorbed. The objective of this study was to assess the iron absorption of Aspergillus oryzae grown in FePP (ASP-p) and compare it with FePP and ferrous sulfate (FeSO4)-fortified bouillon cubes. METHODS In 2 single-blinded, crossover studies, healthy women with serum ferritin concentrations less then 40 μg/L were randomly assigned to consume a rice-vegetable meal with iron-fortified chicken bouillon. Subjects in study I (n = 17, 18-26 y) consumed iron from both iron sources as 57FePP and 58ASP-p (intrinsically labeled with 58FePP) with a meal containing 4.2 mg of total iron provided for 3 d. Study II (n = 18, 18-29 y) was similar except that subjects consumed 57FeSO4 and 58ASP-p. Whole-blood stable isotope enrichment after 14 d was used to measure fractional iron absorption. Hemoglobin, hematocrit, serum ferritin, hepcidin, and serum C-reactive protein were analyzed at baseline and at 14 d.
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