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  • Phonon transport in the nano-system has been studied using well-designed nanostructured materials to observe and control the interesting phonon behaviors like ballistic phonon transport. Recently, we observed drastic thermal conductivity reduction in the films containing well-controlled nanodots. Here, we investigate whether this comes from the interference effect in ballistic phonon transport by comparing the thermal properties of the Si or Si0.75Ge0.25 films containing Ge nanodots. The experimentally-obtained thermal resistance of the nanodot layer shows peculiar nanodot size dependence in the Si films and a constant value in the SiGe films. From the phonon simulation results, interestingly, it is clearly found that in the nanostructured Si film, phonons travel in a non-diffusive way (ballistic phonon transport). On the other hand, in the nanostructured SiGe film, although simple diffusive phonon transport occurs, extremely-low thermal conductivity (∼0.81 W m-1 K-1) close to that of amorphous Si0.7Ge0.3 (∼0.7 W m-1 K-1) is achieved due to the combination of the alloy phonon scattering and Ge nanodot scattering.Mass spectrometry (MS)-based proteomics has enabled the identification and quantification of thousands of proteins from complex proteomes in a single experiment. However, its performance for mass-limited proteome samples (e.g., single cells and tissue samples from laser capture microdissection) is still not satisfying. The development of novel proteomic methodologies with better overall sensitivity is vital. During the last several years, substantial technical progress has been achieved for the preparation and liquid-phase separation-MS characterization of mass-limited proteome samples. In this review, we summarize recent technological progress of sample preparation, liquid chromatography (LC)-MS, capillary zone electrophoresis (CZE)-MS and MS instrumentation for bottom-up proteomics of trace biological samples, highlight some exciting applications of the novel techniques for single-cell proteomics, and provide a very brief perspective about the field at the end.Pharmacological chaperones (PCs) are low-molecular weight chemical molecules used in patients for the treatment of some rare diseases caused primarily by protein instability. A controlled and on-demand release of PCs via nanoparticles is an alternative for cases in which long treatments are needed and prolonged oral administration could have adverse effects. In this work, pyrimethamine (PYR), which is a potent PC consisting of pyrimidine-2,4-diamine substituted at position 5 by a p-chlorophenyl group and at position 6 by an ethyl group, was successfully loaded in electroresponsive poly(3,4-ethylenedioxythiophene) nanoparticles (PEDOT NPs). The PYR-loading capacity was 11.4 ± 1.5%, with both loaded and unloaded PEDOT NPs exhibiting similar sizes (215 ± 3 and 203 ± 1 nm, respectively) and net surface charges (-26 ± 7 and -29 ± 6 mV, respectively). In the absence of electrical stimulus, the release of PC from loaded NPs is very low (1.6% in 24 h and 18% in 80 days) in aqueous environments. Instead, electrical stimuli that sustained for 30 min enhanced the release of PYR, which was ∼50% when the voltage was scanned from -0.5 V to 0.5 V (cyclic voltammetry) and ∼35% when a constant voltage of 1.0 V was applied (chronoamperometry).The photodissociation dynamics of strong-field ionized methyl iodide (CH3I) were probed using intense extreme ultraviolet (XUV) radiation produced by the SPring-8 Angstrom Compact free electron LAser (SACLA). Strong-field ionization and subsequent fragmentation of CH3I was initiated by an intense femtosecond infrared (IR) pulse. The ensuing fragmentation and charge transfer processes following multiple ionization by the XUV pulse at a range of pump-probe delays were followed in a multi-mass ion velocity-map imaging (VMI) experiment. Simultaneous imaging of a wide range of resultant ions allowed for additional insight into the complex dynamics by elucidating correlations between the momenta of different fragment ions using time-resolved recoil-frame covariance imaging analysis. The comprehensive picture of the photodynamics that can be extracted provides promising evidence that the techniques described here could be applied to study ultrafast photochemistry in a range of molecular systems at high count rates using state-of-the-art advanced light sources.Enzyme-nanoparticle interactions can give rise to a range of new phenomena, most notably significant enzymatic rate enhancement. Accordingly, the careful study and optimization of such systems is likely to give rise to advanced biosensing applications. Herein, we report a systematic study of the interactions between nuclease enzymes and oligonucleotide-coated gold nanoparticles (spherical nucleic acids, SNAs), with the aim of revealing phenomena worthy of evolution into functional nanosystems. Specifically, we study two nucleases, an exonuclease (ExoIII) and an endonuclease (Nt.BspQI), via fluorescence-based kinetic experiments, varying parameters including enzyme and substrate concentrations, and nanoparticle size and surface coverage in non-recycling and a recycling formats. We demonstrate the tuning of nuclease activity by SNA characteristics and show that the modular units of SNAs can be leveraged to either accelerate or suppress nuclease kinetics. Additionally, we observe that the enzymes are capable of cleaving restriction sites buried deep in the oligonucleotide surface layer and that enzymatic rate enhancement occurs in the target recycling format but not in the non-recycling format. Furthermore, we demonstrate a new SNA phenomenon, we term 'target stacking', whereby nucleic acid hybridization efficiency increases as enzyme cleavage proceeds during the beginning of a reaction. This investigation provides important data to guide the design of novel SNAs in biosensing and in vitro diagnostic applications.Tunable electronic properties of low-dimensional materials have been the object of extensive research, as such properties are highly desirable in order to provide flexibility in the design and optimization of functional devices. In this study, we account for the fact that such properties can be tuned by embedding diverse metal atoms and theoretically study a series of new organometallic porous sheets based on two-dimensional tetraoxa[8]circulene (TOC) polymers doped with alkali or alkaline-earth metals. The results reveal that the metal-decorated sheets change their electronic structure from semiconducting to metallic behaviour due to n-doping. Complete active space self-consistent field (CASSCF) calculations reveal a unique open-shell singlet ground state in the TOC-Ca complex, which is formed by two closed-shell species. Moreover, Ca becomes a doublet state, which is promising for magnetic quantum bit applications due to the long spin coherence time. https://www.selleckchem.com/products/cremophor-el.html Ca-doped TOC also demonstrates a high density of states in the vicinity of the Fermi level and induced superconductivity.
    Phonon transport in the nano-system has been studied using well-designed nanostructured materials to observe and control the interesting phonon behaviors like ballistic phonon transport. Recently, we observed drastic thermal conductivity reduction in the films containing well-controlled nanodots. Here, we investigate whether this comes from the interference effect in ballistic phonon transport by comparing the thermal properties of the Si or Si0.75Ge0.25 films containing Ge nanodots. The experimentally-obtained thermal resistance of the nanodot layer shows peculiar nanodot size dependence in the Si films and a constant value in the SiGe films. From the phonon simulation results, interestingly, it is clearly found that in the nanostructured Si film, phonons travel in a non-diffusive way (ballistic phonon transport). On the other hand, in the nanostructured SiGe film, although simple diffusive phonon transport occurs, extremely-low thermal conductivity (∼0.81 W m-1 K-1) close to that of amorphous Si0.7Ge0.3 (∼0.7 W m-1 K-1) is achieved due to the combination of the alloy phonon scattering and Ge nanodot scattering.Mass spectrometry (MS)-based proteomics has enabled the identification and quantification of thousands of proteins from complex proteomes in a single experiment. However, its performance for mass-limited proteome samples (e.g., single cells and tissue samples from laser capture microdissection) is still not satisfying. The development of novel proteomic methodologies with better overall sensitivity is vital. During the last several years, substantial technical progress has been achieved for the preparation and liquid-phase separation-MS characterization of mass-limited proteome samples. In this review, we summarize recent technological progress of sample preparation, liquid chromatography (LC)-MS, capillary zone electrophoresis (CZE)-MS and MS instrumentation for bottom-up proteomics of trace biological samples, highlight some exciting applications of the novel techniques for single-cell proteomics, and provide a very brief perspective about the field at the end.Pharmacological chaperones (PCs) are low-molecular weight chemical molecules used in patients for the treatment of some rare diseases caused primarily by protein instability. A controlled and on-demand release of PCs via nanoparticles is an alternative for cases in which long treatments are needed and prolonged oral administration could have adverse effects. In this work, pyrimethamine (PYR), which is a potent PC consisting of pyrimidine-2,4-diamine substituted at position 5 by a p-chlorophenyl group and at position 6 by an ethyl group, was successfully loaded in electroresponsive poly(3,4-ethylenedioxythiophene) nanoparticles (PEDOT NPs). The PYR-loading capacity was 11.4 ± 1.5%, with both loaded and unloaded PEDOT NPs exhibiting similar sizes (215 ± 3 and 203 ± 1 nm, respectively) and net surface charges (-26 ± 7 and -29 ± 6 mV, respectively). In the absence of electrical stimulus, the release of PC from loaded NPs is very low (1.6% in 24 h and 18% in 80 days) in aqueous environments. Instead, electrical stimuli that sustained for 30 min enhanced the release of PYR, which was ∼50% when the voltage was scanned from -0.5 V to 0.5 V (cyclic voltammetry) and ∼35% when a constant voltage of 1.0 V was applied (chronoamperometry).The photodissociation dynamics of strong-field ionized methyl iodide (CH3I) were probed using intense extreme ultraviolet (XUV) radiation produced by the SPring-8 Angstrom Compact free electron LAser (SACLA). Strong-field ionization and subsequent fragmentation of CH3I was initiated by an intense femtosecond infrared (IR) pulse. The ensuing fragmentation and charge transfer processes following multiple ionization by the XUV pulse at a range of pump-probe delays were followed in a multi-mass ion velocity-map imaging (VMI) experiment. Simultaneous imaging of a wide range of resultant ions allowed for additional insight into the complex dynamics by elucidating correlations between the momenta of different fragment ions using time-resolved recoil-frame covariance imaging analysis. The comprehensive picture of the photodynamics that can be extracted provides promising evidence that the techniques described here could be applied to study ultrafast photochemistry in a range of molecular systems at high count rates using state-of-the-art advanced light sources.Enzyme-nanoparticle interactions can give rise to a range of new phenomena, most notably significant enzymatic rate enhancement. Accordingly, the careful study and optimization of such systems is likely to give rise to advanced biosensing applications. Herein, we report a systematic study of the interactions between nuclease enzymes and oligonucleotide-coated gold nanoparticles (spherical nucleic acids, SNAs), with the aim of revealing phenomena worthy of evolution into functional nanosystems. Specifically, we study two nucleases, an exonuclease (ExoIII) and an endonuclease (Nt.BspQI), via fluorescence-based kinetic experiments, varying parameters including enzyme and substrate concentrations, and nanoparticle size and surface coverage in non-recycling and a recycling formats. We demonstrate the tuning of nuclease activity by SNA characteristics and show that the modular units of SNAs can be leveraged to either accelerate or suppress nuclease kinetics. Additionally, we observe that the enzymes are capable of cleaving restriction sites buried deep in the oligonucleotide surface layer and that enzymatic rate enhancement occurs in the target recycling format but not in the non-recycling format. Furthermore, we demonstrate a new SNA phenomenon, we term 'target stacking', whereby nucleic acid hybridization efficiency increases as enzyme cleavage proceeds during the beginning of a reaction. This investigation provides important data to guide the design of novel SNAs in biosensing and in vitro diagnostic applications.Tunable electronic properties of low-dimensional materials have been the object of extensive research, as such properties are highly desirable in order to provide flexibility in the design and optimization of functional devices. In this study, we account for the fact that such properties can be tuned by embedding diverse metal atoms and theoretically study a series of new organometallic porous sheets based on two-dimensional tetraoxa[8]circulene (TOC) polymers doped with alkali or alkaline-earth metals. The results reveal that the metal-decorated sheets change their electronic structure from semiconducting to metallic behaviour due to n-doping. Complete active space self-consistent field (CASSCF) calculations reveal a unique open-shell singlet ground state in the TOC-Ca complex, which is formed by two closed-shell species. Moreover, Ca becomes a doublet state, which is promising for magnetic quantum bit applications due to the long spin coherence time. https://www.selleckchem.com/products/cremophor-el.html Ca-doped TOC also demonstrates a high density of states in the vicinity of the Fermi level and induced superconductivity.
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  • Type 2 Diabetes Mellitus (T2DM) is a chronic disease which corresponds to 90% of the worldwide cases of diabetes, mainly due to epigenetic factors such as unhealthy lifestyles. First line therapeutic approaches are based on lifestyle changes, most of the time complemented with medication mostly associated with several side effects and high costs. As a result, the scientific community is constantly working for the discovery and development of natural therapeutic strategies that provide lower financial impact and minimize side effects. This review focus on these nature-based therapeutic strategies for prevention and control of T2DM, with a special emphasis on natural compounds that present pharmacological activity as dipeptidyl peptidase-4 (DPP4), alpha-amylase, alpha-glucosidase, lipase, and protein tyrosine phosphatase 1B (PTP1B) inhibitors.This experimental research highlights the applicability of laser cutting to cement-based materials using multimode fiber lasers. A 9 kW multimode fiber laser is used, and the experimental variables are the water-to-cement ratio, laser speed, and material compositions such as cement paste, cement mortar and ultra high performance concrete (UHPC). The laser cutting performance on the cement-based materials is investigated in the downward laser direction. The kerf width and penetration depth of the cement-based materials are quantitatively evaluated with the parameters in the surface and cross section of the specimens after the laser cutting. Moreover, the material removal zone of each specimen is compared in terms of the penetration shapes in the cross-sectional view. Based on experimental observations, the interaction mechanism between the laser and cement-based materials is proposed.Autotaxin (ATX) is considered as an interesting drug target for the therapy of several diseases. The goal of the research was to detect new ATX inhibitors which have novel scaffolds by using virtual screening. First, based on two diverse receptor-ligand complexes, 14 pharmacophore models were developed, and the 14 models were verified through a big test database. Those pharmacophore models were utilized to accomplish virtual screening. Next, for the purpose of predicting the probable binding poses of compounds and then carrying out further virtual screening, docking-based virtual screening was performed. Moreover, an excellent 3D QSAR model was established, and 3D QSAR-based virtual screening was applied for predicting the activity values of compounds which got through the above two-round screenings. A correlation coefficient r2, which equals 0.988, was supplied by the 3D QSAR model for the training set, and the correlation coefficient r2 equaling 0.808 for the test set means that the developed 3D QSAR model is an excellent model. After the filtering was done by the combinatory virtual screening, which is based on the pharmacophore modelling, docking study, and 3D QSAR modelling, we chose nine potent inhibitors with novel scaffolds finally. Furthermore, two potent compounds have been particularly discussed.Changes in a certain parameter are often a few magnitudes smaller than the base value of the parameter, specifying significant requirements for the dynamic range and noise levels of the measurement system. In case of electrical bioimpedance acquisition, the variations can be 1000 times smaller than the entire measured value. Synchronous or lock-in measurement of these variations is discussed in the current paper, and novel measurement solutions are presented. Proposed methods are simple and robust when compared to other applicable solutions. A common feature shared by all members of the group of the proposed solutions is differentiation. It is achieved by calculating the differences between synchronously acquired consecutive samples, with lock-in integration and analog differentiation. All these methods enable inherent separation of variations from the static component of the signal. The variable component of the bioimpedance can, thus, be acquired using the full available dynamic range of the apparatus for its detection. Additive disturbing signals and omnipresent wideband noise are considered and the method for their reduction is proposed.Synovium-induced angiogenesis is central to osteoarthritis (OA) pathogenesis and thus a promising therapeutic target. The adipokine apelin (APLN) is involved in both OA pathogenesis and angiogenesis. We examined the role of APLN in synovium-induced angiogenesis by investigating the crosstalk between APLN and vascular endothelial growth factor (VEGF) expression in human OA synovial fibroblasts (OASFs). We found higher levels of APLN and VEGF expression in OA samples compared with normal samples. APLN-induced stimulation of VEGF expression and VEGF-dependent angiogenesis in OASFs was mitigated by FAK/Src/Akt signaling. APLN also inhibited levels of microRNA-150-5p (miR-150-5p), which represses VEGF production and angiogenesis. Analyses of an OA animal model showed that shAPLN transfection of OASFs rescued pathologic changes in OA cartilage and histology. Here, we found APLN enhances VEGF expression and angiogenesis via FAK/Src/Akt cascade and via downstream suppression of miR-150-5p expression. These findings help to clarify the pathogenesis of adipokine-induced angiogenesis in OA synovium.Diet-related immunometabolic-based diseases are associated with chronic inflammation in metabolic tissues, and infiltrated macrophages have been suggested as mediators for tissue- damaging inflammation. Growing evidence implicates Chenopodium quinoa and Salvia hispanica L. https://www.selleckchem.com/products/sr18662.html as important contributors to immunonutritional health. However, the functional roles of the immunonutritional protease inhibitors (PPIs) found in these crops on the macrophages' metabolic and phenotypic adaptation remain to be elucidated. The salt soluble fraction of proteins was extracted and analyzed confirming the presence of 11S and 2S albumin. The less then 30 kDa fraction of the extract from both crops was subjected to simulated gastrointestinal digestion, where (RP-LC-MS/MS analyses) polypeptides from 2S-type of proteins were found, along with the 2S albumin (13 kDa) for S. hispanica in the bioaccessible fraction (BAF). Using human-like macrophage cells to deepen our understanding of the modulatory effects of this BAF, FACS analyses revealed their potential as TLR4 agonists, favoring increased phenotypic CD68/CD206 ratios.
    Type 2 Diabetes Mellitus (T2DM) is a chronic disease which corresponds to 90% of the worldwide cases of diabetes, mainly due to epigenetic factors such as unhealthy lifestyles. First line therapeutic approaches are based on lifestyle changes, most of the time complemented with medication mostly associated with several side effects and high costs. As a result, the scientific community is constantly working for the discovery and development of natural therapeutic strategies that provide lower financial impact and minimize side effects. This review focus on these nature-based therapeutic strategies for prevention and control of T2DM, with a special emphasis on natural compounds that present pharmacological activity as dipeptidyl peptidase-4 (DPP4), alpha-amylase, alpha-glucosidase, lipase, and protein tyrosine phosphatase 1B (PTP1B) inhibitors.This experimental research highlights the applicability of laser cutting to cement-based materials using multimode fiber lasers. A 9 kW multimode fiber laser is used, and the experimental variables are the water-to-cement ratio, laser speed, and material compositions such as cement paste, cement mortar and ultra high performance concrete (UHPC). The laser cutting performance on the cement-based materials is investigated in the downward laser direction. The kerf width and penetration depth of the cement-based materials are quantitatively evaluated with the parameters in the surface and cross section of the specimens after the laser cutting. Moreover, the material removal zone of each specimen is compared in terms of the penetration shapes in the cross-sectional view. Based on experimental observations, the interaction mechanism between the laser and cement-based materials is proposed.Autotaxin (ATX) is considered as an interesting drug target for the therapy of several diseases. The goal of the research was to detect new ATX inhibitors which have novel scaffolds by using virtual screening. First, based on two diverse receptor-ligand complexes, 14 pharmacophore models were developed, and the 14 models were verified through a big test database. Those pharmacophore models were utilized to accomplish virtual screening. Next, for the purpose of predicting the probable binding poses of compounds and then carrying out further virtual screening, docking-based virtual screening was performed. Moreover, an excellent 3D QSAR model was established, and 3D QSAR-based virtual screening was applied for predicting the activity values of compounds which got through the above two-round screenings. A correlation coefficient r2, which equals 0.988, was supplied by the 3D QSAR model for the training set, and the correlation coefficient r2 equaling 0.808 for the test set means that the developed 3D QSAR model is an excellent model. After the filtering was done by the combinatory virtual screening, which is based on the pharmacophore modelling, docking study, and 3D QSAR modelling, we chose nine potent inhibitors with novel scaffolds finally. Furthermore, two potent compounds have been particularly discussed.Changes in a certain parameter are often a few magnitudes smaller than the base value of the parameter, specifying significant requirements for the dynamic range and noise levels of the measurement system. In case of electrical bioimpedance acquisition, the variations can be 1000 times smaller than the entire measured value. Synchronous or lock-in measurement of these variations is discussed in the current paper, and novel measurement solutions are presented. Proposed methods are simple and robust when compared to other applicable solutions. A common feature shared by all members of the group of the proposed solutions is differentiation. It is achieved by calculating the differences between synchronously acquired consecutive samples, with lock-in integration and analog differentiation. All these methods enable inherent separation of variations from the static component of the signal. The variable component of the bioimpedance can, thus, be acquired using the full available dynamic range of the apparatus for its detection. Additive disturbing signals and omnipresent wideband noise are considered and the method for their reduction is proposed.Synovium-induced angiogenesis is central to osteoarthritis (OA) pathogenesis and thus a promising therapeutic target. The adipokine apelin (APLN) is involved in both OA pathogenesis and angiogenesis. We examined the role of APLN in synovium-induced angiogenesis by investigating the crosstalk between APLN and vascular endothelial growth factor (VEGF) expression in human OA synovial fibroblasts (OASFs). We found higher levels of APLN and VEGF expression in OA samples compared with normal samples. APLN-induced stimulation of VEGF expression and VEGF-dependent angiogenesis in OASFs was mitigated by FAK/Src/Akt signaling. APLN also inhibited levels of microRNA-150-5p (miR-150-5p), which represses VEGF production and angiogenesis. Analyses of an OA animal model showed that shAPLN transfection of OASFs rescued pathologic changes in OA cartilage and histology. Here, we found APLN enhances VEGF expression and angiogenesis via FAK/Src/Akt cascade and via downstream suppression of miR-150-5p expression. These findings help to clarify the pathogenesis of adipokine-induced angiogenesis in OA synovium.Diet-related immunometabolic-based diseases are associated with chronic inflammation in metabolic tissues, and infiltrated macrophages have been suggested as mediators for tissue- damaging inflammation. Growing evidence implicates Chenopodium quinoa and Salvia hispanica L. https://www.selleckchem.com/products/sr18662.html as important contributors to immunonutritional health. However, the functional roles of the immunonutritional protease inhibitors (PPIs) found in these crops on the macrophages' metabolic and phenotypic adaptation remain to be elucidated. The salt soluble fraction of proteins was extracted and analyzed confirming the presence of 11S and 2S albumin. The less then 30 kDa fraction of the extract from both crops was subjected to simulated gastrointestinal digestion, where (RP-LC-MS/MS analyses) polypeptides from 2S-type of proteins were found, along with the 2S albumin (13 kDa) for S. hispanica in the bioaccessible fraction (BAF). Using human-like macrophage cells to deepen our understanding of the modulatory effects of this BAF, FACS analyses revealed their potential as TLR4 agonists, favoring increased phenotypic CD68/CD206 ratios.
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  • Hepatitis C virus (HCV) infection is a major cause of chronic liver disease and associated cirrhosis, and hepatocellular carcinoma worldwide. At present, there is no prophylactic vaccine against HCV due to the lack of in vivo and in vitro model systems. Although most recombinants of all major HCV genotypes replicate in Huh-7 cell line and derivatives, these cells are human hepatoma-derived cell line. Therefore, the development of un-tumor-derived cell systems facilitating the entire HCV life cycle is urgently needed. In this study, we aimed to establish a novel tree shrew-derived bone marrow-derived mesenchymal stem cell (BM-MSC) system to reconstruct the HCV life cycle. We transduction cluster of differentiation 81 (CD81), occludin (OCLN), and microRNA-122 (miR-122) into BM-****, then used a well-established HCV, produced from the J6/JFH1-Huh7.5.1 culture system, to infect the cells. We observed that BM-**** transduction with CD81/OCLN or CD81/OCLN/miR-122 support HCV RNA replication and infectious virus production. We also found that the addition of exogenous vascular endothelial growth factor (VEGF) can enhance HCV infectivity in BM-****, with HCV virus load up to 105 copies/mL. In conclusion, we identified the minimum essential factors required for HCV replication in tree shrew-derived nonhuman nonhepatic BM-****. Further, we identified that exogenous addition of VEGF, and exogenous expression of CD81, OCLN, and miR-122, facilitates efficient viral replication and production of infectious particles. Our results describe a novel cell system capable of supporting the entire HCV life cycle, which may provide an essential tool for anti-HCV drug discovery, vaccine development, and study of pathogenesis. © 2020 Wiley Periodicals, Inc.OBJECTIVES Evodiamine (Evo) possesses strong anti-inflammatory activity. In this study, we determine the antiarthritic effect of Evo. METHODS Evo was administered to rats with adjuvant-induced arthritis (AA). We evaluated arthritis symptoms & histopathological changes and measured inflammatory cell infiltration, pro-inflammatory cytokine production and Th17 & Treg percentages in arthritic rats. KEY FINDINGS Evo significantly improved the clinical signs of AA in rats, including decreases in paw swelling, the polyarthritis index and the number of swollen paw joints. Based on the histopathological analysis, Evo improved synovial inflammation and bone injury by inhibiting inflammatory cell infiltration, synoviocyte proliferation, pannus formation and cartilage erosion. Furthermore, the numbers of synovial CD3+ or CD68+ inflammatory cells were reduced, and the elevated levels of tumour necrosis factor-α, interleukin-1β (IL-1β) and IL-6 were restored to control levels by the Evo treatment. In addition, Evo therapy regulated the abnormal differentiation of Treg and Th17 cells, decreasing IL-17 production and increasing IL-10 levels. Finally, Evo inhibited Stat3 phosphorylation and induced Stat5 phosphorylation in rats with AA. CONCLUSIONS Based on our results, Evo is a promising antiarthritic agent, potentially due to its inhibitory effect on synovial inflammation and regulatory effects on Treg and Th17 differentiation. © 2020 Royal Pharmaceutical Society.Behavioral economic theory has proved useful for understanding the influence of delay and probability on sexual health decision-making. Demand is another principle at the intersection of microeconomics and psychology that has helped advance research relevant to health behaviors. The purpose of the present study was to develop and test a demand measure related to sexual health decision-making and the influence of sexually transmitted infection (STI) risk. Participants (N = 438) recruited using Amazon Mechanical Turk completed a commodity purchase task assessing hypothetical condom demand. Condom demand was evaluated at varied prices for use with hypothetical sexual partners that varied in STI risk. https://www.selleckchem.com/products/Taurine.html Demand was characterized by prototypic decreases in consumption with increases in cost. Higher partner STI risk was associated with greater intentions for condom-protected sex at no cost and smaller decreases in condom demand with increases in cost. Price sensitivity was also related to individual difference factors relevant to sexual health (e.g., alcohol use severity, lower STI knowledge). This study supports the utility of a condom purchase task for indexing condom valuation and capturing individual difference and contextual risk factors relevant to STI transmission. Future studies may leverage this methodology as a means to study sexual health decision-making. © 2020 Society for the Experimental Analysis of Behavior.INTRODUCTION The aim of this study was to investigate reasons why people consulted an occupational therapist following cancer treatment, and to examine the outcome of occupational therapy interventions, in the context of multidisciplinary rehabilitation. METHODS Data from 181 patients were collected retrospectively. The International Classification of Human Functioning and Health (ICF) was used to describe the reasons for occupational therapy consultation. Patients had completed the Canadian Occupational Performance Measurement (COPM) before and after the occupational therapy intervention. Change scores were calculated with a 95% confidence interval and a two-sided p-value obtained from a paired t-test. RESULTS The reasons for occupational therapy consultation were predominantly within the ICF domain "Activities and Participation". On average, patients improved 3.0 points (95% CI 2.8-3.2) on the performance scale of the COPM, and 3.4 points (95% CI 3.2-3.7) on the satisfaction scale (both p =  less then .001). CONCLUSION The result of this study supports the added value of occupational therapy to cancer rehabilitation, and emphasise the positive effect of occupational therapy on everyday functioning. Controlled clinical studies are needed to strengthen the evidence. © 2020 Occupational Therapy Australia.PURPOSE Tattoo fiducials are commonly used in radiotherapy patient alignment, and recent studies have examined the use of UV-excited luminescent tattoo ink as a cosmetic substitute to make these visible under UV illumination. The goal of this study was to show how luminescent tattoo inks could be excited with MV radiation and imaged during beam delivery for direct visualization of field position. METHODS A survey of nine UV-sensitive tattoo inks with various emission spectra were investigated using both UV and MV excitation. Images of liquid solutions were collected under MV excitation using an intensified-CMOS imager. Solid skin-simulating phantoms were imaged with both surface-painted ink and in situ tattooing during dose delivery by both a clinical linear accelerator and cobalt-60 source. RESULTS The UV inks have peak fluorescence emission ranging from approximately 440 to 600 nm with lifetimes near 11-16 μs. The luminescence intensity is approximately 6x higher during the x-ray pulse than after the pulse, however, the signal-to-noise is only approximately twice as large.
    Hepatitis C virus (HCV) infection is a major cause of chronic liver disease and associated cirrhosis, and hepatocellular carcinoma worldwide. At present, there is no prophylactic vaccine against HCV due to the lack of in vivo and in vitro model systems. Although most recombinants of all major HCV genotypes replicate in Huh-7 cell line and derivatives, these cells are human hepatoma-derived cell line. Therefore, the development of un-tumor-derived cell systems facilitating the entire HCV life cycle is urgently needed. In this study, we aimed to establish a novel tree shrew-derived bone marrow-derived mesenchymal stem cell (BM-MSC) system to reconstruct the HCV life cycle. We transduction cluster of differentiation 81 (CD81), occludin (OCLN), and microRNA-122 (miR-122) into BM-MSCs, then used a well-established HCV, produced from the J6/JFH1-Huh7.5.1 culture system, to infect the cells. We observed that BM-MSCs transduction with CD81/OCLN or CD81/OCLN/miR-122 support HCV RNA replication and infectious virus production. We also found that the addition of exogenous vascular endothelial growth factor (VEGF) can enhance HCV infectivity in BM-MSCs, with HCV virus load up to 105 copies/mL. In conclusion, we identified the minimum essential factors required for HCV replication in tree shrew-derived nonhuman nonhepatic BM-MSCs. Further, we identified that exogenous addition of VEGF, and exogenous expression of CD81, OCLN, and miR-122, facilitates efficient viral replication and production of infectious particles. Our results describe a novel cell system capable of supporting the entire HCV life cycle, which may provide an essential tool for anti-HCV drug discovery, vaccine development, and study of pathogenesis. © 2020 Wiley Periodicals, Inc.OBJECTIVES Evodiamine (Evo) possesses strong anti-inflammatory activity. In this study, we determine the antiarthritic effect of Evo. METHODS Evo was administered to rats with adjuvant-induced arthritis (AA). We evaluated arthritis symptoms & histopathological changes and measured inflammatory cell infiltration, pro-inflammatory cytokine production and Th17 & Treg percentages in arthritic rats. KEY FINDINGS Evo significantly improved the clinical signs of AA in rats, including decreases in paw swelling, the polyarthritis index and the number of swollen paw joints. Based on the histopathological analysis, Evo improved synovial inflammation and bone injury by inhibiting inflammatory cell infiltration, synoviocyte proliferation, pannus formation and cartilage erosion. Furthermore, the numbers of synovial CD3+ or CD68+ inflammatory cells were reduced, and the elevated levels of tumour necrosis factor-α, interleukin-1β (IL-1β) and IL-6 were restored to control levels by the Evo treatment. In addition, Evo therapy regulated the abnormal differentiation of Treg and Th17 cells, decreasing IL-17 production and increasing IL-10 levels. Finally, Evo inhibited Stat3 phosphorylation and induced Stat5 phosphorylation in rats with AA. CONCLUSIONS Based on our results, Evo is a promising antiarthritic agent, potentially due to its inhibitory effect on synovial inflammation and regulatory effects on Treg and Th17 differentiation. © 2020 Royal Pharmaceutical Society.Behavioral economic theory has proved useful for understanding the influence of delay and probability on sexual health decision-making. Demand is another principle at the intersection of microeconomics and psychology that has helped advance research relevant to health behaviors. The purpose of the present study was to develop and test a demand measure related to sexual health decision-making and the influence of sexually transmitted infection (STI) risk. Participants (N = 438) recruited using Amazon Mechanical Turk completed a commodity purchase task assessing hypothetical condom demand. Condom demand was evaluated at varied prices for use with hypothetical sexual partners that varied in STI risk. https://www.selleckchem.com/products/Taurine.html Demand was characterized by prototypic decreases in consumption with increases in cost. Higher partner STI risk was associated with greater intentions for condom-protected sex at no cost and smaller decreases in condom demand with increases in cost. Price sensitivity was also related to individual difference factors relevant to sexual health (e.g., alcohol use severity, lower STI knowledge). This study supports the utility of a condom purchase task for indexing condom valuation and capturing individual difference and contextual risk factors relevant to STI transmission. Future studies may leverage this methodology as a means to study sexual health decision-making. © 2020 Society for the Experimental Analysis of Behavior.INTRODUCTION The aim of this study was to investigate reasons why people consulted an occupational therapist following cancer treatment, and to examine the outcome of occupational therapy interventions, in the context of multidisciplinary rehabilitation. METHODS Data from 181 patients were collected retrospectively. The International Classification of Human Functioning and Health (ICF) was used to describe the reasons for occupational therapy consultation. Patients had completed the Canadian Occupational Performance Measurement (COPM) before and after the occupational therapy intervention. Change scores were calculated with a 95% confidence interval and a two-sided p-value obtained from a paired t-test. RESULTS The reasons for occupational therapy consultation were predominantly within the ICF domain "Activities and Participation". On average, patients improved 3.0 points (95% CI 2.8-3.2) on the performance scale of the COPM, and 3.4 points (95% CI 3.2-3.7) on the satisfaction scale (both p =  less then .001). CONCLUSION The result of this study supports the added value of occupational therapy to cancer rehabilitation, and emphasise the positive effect of occupational therapy on everyday functioning. Controlled clinical studies are needed to strengthen the evidence. © 2020 Occupational Therapy Australia.PURPOSE Tattoo fiducials are commonly used in radiotherapy patient alignment, and recent studies have examined the use of UV-excited luminescent tattoo ink as a cosmetic substitute to make these visible under UV illumination. The goal of this study was to show how luminescent tattoo inks could be excited with MV radiation and imaged during beam delivery for direct visualization of field position. METHODS A survey of nine UV-sensitive tattoo inks with various emission spectra were investigated using both UV and MV excitation. Images of liquid solutions were collected under MV excitation using an intensified-CMOS imager. Solid skin-simulating phantoms were imaged with both surface-painted ink and in situ tattooing during dose delivery by both a clinical linear accelerator and cobalt-60 source. RESULTS The UV inks have peak fluorescence emission ranging from approximately 440 to 600 nm with lifetimes near 11-16 μs. The luminescence intensity is approximately 6x higher during the x-ray pulse than after the pulse, however, the signal-to-noise is only approximately twice as large.
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  • The Drosophila nervous system is a valuable model to examine the mechanisms of activity-dependent synaptic modification (plasticity) owing to its relatively simple organization and the availability of powerful genetic tools. The larval neuromuscular junction (NMJ) in particular is an accessible model for the study of synaptic development and plasticity. In addition to the NMJ, huge strides have also been made on understanding activity-dependent synaptic plasticity in the Drosophila olfactory and visual systems. In this review, we focus mainly on the underlying processes of activity-dependent synaptic plasticity at both pre-synaptic and post-synaptic terminals, and summarize current knowledge on activity-dependent synaptic plasticity in different parts of the Drosophila melanogaster nervous system (larval NMJ, olfactory system, larval visual system, and adult visual system). We also examine links between synaptic development and activity-dependent synaptic plasticity, and the relationships between morphological and physiological plasticity. We provide a point of view from which we discern that the underlying mechanism of activity-dependent plasticity may be common throughout the nervous systems in Drosophila melanogaster. Copyright © 2020 Bai and Suzuki.Ticks and the diseases they transmit are of huge veterinary, medical and economic importance worldwide. Control of ticks attacking livestock and companion animals is achieved primarily by application of chemical or plant-based acaricides. However, ticks can rapidly develop resistance to any new product brought onto the market, necessitating an ongoing search for novel active compounds and alternative approaches to tick control. Many aspects of tick and tick-borne pathogen research have been facilitated by the application of continuous cell lines derived from some of the most economically important tick species. These include cell lines derived from acaricide-susceptible and resistant ticks, cell sub-lines with in vitro-generated acaricide resistance, and genetically modified tick cells. Although not a replacement for the whole organism, tick cell lines enable studies at the cellular and molecular level and provide a more accessible, more ethical and less expensive in vitro alternative to in vivo tick feeding experiments. Here we review the role played by tick cell lines in studies on acaricide resistance, mode-of-action of acaricides, identification of potential novel control targets through better understanding of tick metabolism, and anti-tick vaccine development, that may lead to new approaches to control ticks and tick-borne diseases. Copyright © 2020 Al-Rofaai and ****-Sakyi.The strength of cardiorespiratory interactions diminishes with age. Physical exercise can reduce the rate of this trend. Inspiratory muscle training (IMT) is a technique capable of improving cardiorespiratory interactions. This study evaluates the effect of IMT on cardiorespiratory coupling in amateur cyclists. Thirty male young healthy cyclists underwent a sham IMT of very low intensity (SHAM, n = 9), an IMT of moderate intensity at 60% of the maximal inspiratory pressure (MIP60, n = 10) and an IMT of high intensity at the critical inspiratory pressure (CIP, n = 11). Electrocardiogram, non-invasive arterial pressure, and thoracic respiratory movement (RM) were recorded before (PRE) and after (POST) training at rest in supine position (REST) and during active standing (STAND). The beat-to-beat series of heart period (HP) and systolic arterial pressure (SAP) were analyzed with the RM signal via a traditional non-causal approach, such as squared coherence function, and via a causal model-based transfer entropy in MIP60 group might be the genuine effect of some rearrangements at the level of central respiratory network and its interactions with sympathetic drive and vagal activity. Copyright © 2020 Abreu, Catai, Cairo, Rehder-Santos, Silva, Signini, Sakaguchi and Porta.Ostrinia furnacalis, an important pest of corn, has substantial detrimental effects on corn production. The mitogen-activated protein kinase (MAPK) signaling pathway plays a pivotal role in an insect's resistance to environmental stress. The expression levels of JNK and p38 have been well recorded in several insects under different environmental stressors, at different developmental stages, and in various tissue types; however, there is limited information on JNK and p38 in agricultural insects. To clarify the mechanism whereby O. furnacalis responds to environmental stress, we cloned JNK and p38 from O. https://www.selleckchem.com/products/AZD1152-HQPA.html furnacalis and subsequently named them OfJNK and Ofp38, respectively. Further, we examined the expression levels of OfJNK and Ofp38 under different environmental stressors. In this study, we obtained full-length sequences of OfJNK and Ofp38, and RT-qPCR results showed that these genes were expressed at all developmental stages, in various tissues (head, chest, abdomen, leg, wing, antennae, compound eye, midgut, and ovary) and under different environmental stressors (4°C and ultraviolet A treatment for 0, 30, 60, 90, and 120 min). The expression levels of OfJNK and Ofp38 were relatively higher in eggs and 3-day-old adult females than in other developmental stages. Moreover, the expression level of OfJNK was higher in the wings than in other tissues, whereas that of Ofp38 was significantly higher in the ovaries than in other tissues. OfJNK and Ofp38 showed high expression 90 min after being subjected to treatment at 4°C and ultraviolet A irradiation; the expression of Ofp38 peaked at 30 min, whereas that of OfJNK peaked at 60 min. These results indicate that O. furnacalis differs in terms of its response under different environmental stressors. In summary, our results will provide a foundation for additional research needed to determine the role of the MAPK signaling pathway and the underlying mechanisms by which it shows resistance to environmental stresses in insects. Copyright © 2020 Su, Meng, Yang and Zhang.The non-linear stress-strain behavior of uniaxially-stretched lung parenchyma is thought to be an emergent phenomenon arising from the ensemble behavior of its microscopic constituents. Such behavior includes the alignment and elongation of randomly oriented alveolar walls with initially flaccid fibers in the direction of strain. To account for the link between microscopic wall behavior and the macroscopic stress-strain curve, we developed an analytical model that represents both alignment and elongation of alveolar walls during uniaxial stretching. The model includes the kinetics and mechanical behavior of randomly oriented elastic alveolar walls that have a bending stiffness at their intersections. The alignment and stretch of the walls following incremental stretch of the tissue were determined based on energy minimization, and the total stress was obtained by differentiating the total energy density with respect to strain. The stress-strain curves predicted by the model were comparable to curves generated by a previously published numerical alveolar network model.
    The Drosophila nervous system is a valuable model to examine the mechanisms of activity-dependent synaptic modification (plasticity) owing to its relatively simple organization and the availability of powerful genetic tools. The larval neuromuscular junction (NMJ) in particular is an accessible model for the study of synaptic development and plasticity. In addition to the NMJ, huge strides have also been made on understanding activity-dependent synaptic plasticity in the Drosophila olfactory and visual systems. In this review, we focus mainly on the underlying processes of activity-dependent synaptic plasticity at both pre-synaptic and post-synaptic terminals, and summarize current knowledge on activity-dependent synaptic plasticity in different parts of the Drosophila melanogaster nervous system (larval NMJ, olfactory system, larval visual system, and adult visual system). We also examine links between synaptic development and activity-dependent synaptic plasticity, and the relationships between morphological and physiological plasticity. We provide a point of view from which we discern that the underlying mechanism of activity-dependent plasticity may be common throughout the nervous systems in Drosophila melanogaster. Copyright © 2020 Bai and Suzuki.Ticks and the diseases they transmit are of huge veterinary, medical and economic importance worldwide. Control of ticks attacking livestock and companion animals is achieved primarily by application of chemical or plant-based acaricides. However, ticks can rapidly develop resistance to any new product brought onto the market, necessitating an ongoing search for novel active compounds and alternative approaches to tick control. Many aspects of tick and tick-borne pathogen research have been facilitated by the application of continuous cell lines derived from some of the most economically important tick species. These include cell lines derived from acaricide-susceptible and resistant ticks, cell sub-lines with in vitro-generated acaricide resistance, and genetically modified tick cells. Although not a replacement for the whole organism, tick cell lines enable studies at the cellular and molecular level and provide a more accessible, more ethical and less expensive in vitro alternative to in vivo tick feeding experiments. Here we review the role played by tick cell lines in studies on acaricide resistance, mode-of-action of acaricides, identification of potential novel control targets through better understanding of tick metabolism, and anti-tick vaccine development, that may lead to new approaches to control ticks and tick-borne diseases. Copyright © 2020 Al-Rofaai and Bell-Sakyi.The strength of cardiorespiratory interactions diminishes with age. Physical exercise can reduce the rate of this trend. Inspiratory muscle training (IMT) is a technique capable of improving cardiorespiratory interactions. This study evaluates the effect of IMT on cardiorespiratory coupling in amateur cyclists. Thirty male young healthy cyclists underwent a sham IMT of very low intensity (SHAM, n = 9), an IMT of moderate intensity at 60% of the maximal inspiratory pressure (MIP60, n = 10) and an IMT of high intensity at the critical inspiratory pressure (CIP, n = 11). Electrocardiogram, non-invasive arterial pressure, and thoracic respiratory movement (RM) were recorded before (PRE) and after (POST) training at rest in supine position (REST) and during active standing (STAND). The beat-to-beat series of heart period (HP) and systolic arterial pressure (SAP) were analyzed with the RM signal via a traditional non-causal approach, such as squared coherence function, and via a causal model-based transfer entropy in MIP60 group might be the genuine effect of some rearrangements at the level of central respiratory network and its interactions with sympathetic drive and vagal activity. Copyright © 2020 Abreu, Catai, Cairo, Rehder-Santos, Silva, Signini, Sakaguchi and Porta.Ostrinia furnacalis, an important pest of corn, has substantial detrimental effects on corn production. The mitogen-activated protein kinase (MAPK) signaling pathway plays a pivotal role in an insect's resistance to environmental stress. The expression levels of JNK and p38 have been well recorded in several insects under different environmental stressors, at different developmental stages, and in various tissue types; however, there is limited information on JNK and p38 in agricultural insects. To clarify the mechanism whereby O. furnacalis responds to environmental stress, we cloned JNK and p38 from O. https://www.selleckchem.com/products/AZD1152-HQPA.html furnacalis and subsequently named them OfJNK and Ofp38, respectively. Further, we examined the expression levels of OfJNK and Ofp38 under different environmental stressors. In this study, we obtained full-length sequences of OfJNK and Ofp38, and RT-qPCR results showed that these genes were expressed at all developmental stages, in various tissues (head, chest, abdomen, leg, wing, antennae, compound eye, midgut, and ovary) and under different environmental stressors (4°C and ultraviolet A treatment for 0, 30, 60, 90, and 120 min). The expression levels of OfJNK and Ofp38 were relatively higher in eggs and 3-day-old adult females than in other developmental stages. Moreover, the expression level of OfJNK was higher in the wings than in other tissues, whereas that of Ofp38 was significantly higher in the ovaries than in other tissues. OfJNK and Ofp38 showed high expression 90 min after being subjected to treatment at 4°C and ultraviolet A irradiation; the expression of Ofp38 peaked at 30 min, whereas that of OfJNK peaked at 60 min. These results indicate that O. furnacalis differs in terms of its response under different environmental stressors. In summary, our results will provide a foundation for additional research needed to determine the role of the MAPK signaling pathway and the underlying mechanisms by which it shows resistance to environmental stresses in insects. Copyright © 2020 Su, Meng, Yang and Zhang.The non-linear stress-strain behavior of uniaxially-stretched lung parenchyma is thought to be an emergent phenomenon arising from the ensemble behavior of its microscopic constituents. Such behavior includes the alignment and elongation of randomly oriented alveolar walls with initially flaccid fibers in the direction of strain. To account for the link between microscopic wall behavior and the macroscopic stress-strain curve, we developed an analytical model that represents both alignment and elongation of alveolar walls during uniaxial stretching. The model includes the kinetics and mechanical behavior of randomly oriented elastic alveolar walls that have a bending stiffness at their intersections. The alignment and stretch of the walls following incremental stretch of the tissue were determined based on energy minimization, and the total stress was obtained by differentiating the total energy density with respect to strain. The stress-strain curves predicted by the model were comparable to curves generated by a previously published numerical alveolar network model.
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  • fecting the tuning of motivated behaviors. This review analyzes the contribution of the kappa opioid system to the dopaminergic correlates of compulsive behaviors. Copyright © 2020 Escobar, Casanova, Andrés and Fuentealba.Background Obesity is associated with an elevated risk of respiratory infections and inflammatory lung diseases. The objective was to investigate (i) the effects of adipokines (adiponectin (APN), leptin, chemerin, and visfatin) on the production of cytokines by unstimulated and poly(IC)- and TNF-α-activated human primary bronchial epithelial cells (hBECs), (ii) the cells' expression of the APN receptors (AdipoR1 and AdipoR2), and (iii) the cells' production of APN. Methods The hBECs were isolated from patients undergoing surgery for lung carcinoma. The cells were then cultured with human recombinant adipokines in the absence or presence of TNF-α or poly(IC) for 24 h. Supernatant levels of cytokines (IL-6, CCL2, CCL5, CCL20, CXCL1, CXCL8) and APN were measured using ELISAs. The mRNA levels of AdipoR1 and AdipoR2 in hBECs were determined using a real-time quantitative PCR. Results Of the four adipokines tested, only APN significantly influenced the basal production and the TNF-α poly(IC)-induced production of cytokines by hBECs. APN (3-30 µg.ml-1) was associated with greater basal production of IL-6, CCL20, and CXCL8, lower basal production of CCL2 and CXCL1 and no difference in CCL5 production. APN inhibited the poly(IC)-induced production of these five cytokines and the TNF-α-induced production of CCL2 and CXCL1. AdipoR1 and AdipoR2 were both expressed in hBECs. In contrast to human bronchial explants, isolated hBECs did not produce APN. Conclusions The APN concentrations are abnormally low in obese individuals, and this fall may contribute to the susceptibility to viral lung infections and the severity of these infections in obese individuals. Copyright © 2020 Salvator, Grassin-Delyle, Naline, Brollo, Fournier, Couderc and Devillier.The incidences of diabetic mellitus and other metabolic diseases such as hypertension and hyperlipidemia are increasing worldwide; however, the current treatment is not able to control the rapidly increasing trend in diabetes mortality and morbidity. Studies related to the effectiveness of extracts and pure compounds obtained from plants have shown promising responses in preclinical and clinical studies related to these metabolic diseases. Plants belonging to the genus Berberis (Family Berberidaceae) are widely distributed with nearly 550 species worldwide. Extracts and compounds obtained from Berberis species, especially Berberine alkaloid, showed effectiveness in the management of diabetes and other metabolic diseases. Various pharmacological experiments have been performed to evaluate the effects of Berberis extracts, berberine, and its natural and chemically synthesized derivatives against various cell and animal disease models with promising results. Various clinical trials conducted so far also showed preventive effects of Berberis extracts and berberine against metabolic diseases. The present review focuses on i) research updates on traditional uses, ii) phytopharmacology and clinical studies on Berberis species, and iii) active metabolites in the prevention and treatment of diabetes and other metabolic diseases with a detailed mechanism of action. Furthermore, the review critically analyzes current research gaps in the therapeutic use of Berberis species and berberine and provides future recommendations. Copyright © 2020 Belwal, Bisht, Devkota, Ullah, Khan, Pandey, Bhatt and Echeverría.[This corrects the article DOI 10.3389/fnagi.2019.00343.]. Copyright © 2020 Smolek, Cubinkova, Brezovakova, Valachova, Szalay, Zilka and Jadhav.The study investigated the consequences of age-related decline in inhibition processes on intentional switching between bimanual coordination patterns. Fifteen young (24±2.8 years) and 20 older adults (69±5.3 years) performed Stroop tasks and bimanual coordination tasks. Stroop tasks included neutral, congruent, and incongruent conditions. Response time and error rate were measured. Bimanual coordination tasks consisted of performing in-phase (IP) and anti-phase (AP) patterns. Participants were requested to switch as quickly as possible from one pattern to the other, resulting in two different switching directions (AP to IP; IP to AP). Mean and standard deviation (SD) of the continuous relative phase (CRP) were calculated pre- and post-switching for each participant. Total switching time (TST) was measured. The switching phase was also decomposed into reaction time (RT) and reversal time (REvT). Pearson correlation analyses were performed to test for correlations between (i) SD of CRP and response time in Strat inhibition processes are involved in switching between bimanual coordination patterns, at least to trigger the early phase of switching. They also support the hypothesis that inhibition processes are more involved in maintaining the AP pattern and switching to the IP pattern. Finally, age-related changes in switching times seem to be prominently mediated by alterations of inhibition processes. Copyright © 2020 Temprado, Torre, Langeard, Julien-Vintrou, Devillers-Réolon, Sleimen-Malkoun and Berton.An intrinsic problem when using hemodynamic responses for the brain-machine interface is the slow nature of the physiological process. In this paper, a novel method that estimates the oxyhemoglobin changes caused by neuronal activations is proposed and validated. https://www.selleckchem.com/products/methyl-b-cyclodextrin.html In monitoring the time responses of blood-oxygen-level-dependent signals with functional near-infrared spectroscopy (fNIRS), the early trajectories of both oxy- and deoxy-hemoglobins in their phase space are scrutinized. Furthermore, to reduce the detection time, a prediction method based upon a kernel-based recursive least squares (KRLS) algorithm is implemented. In validating the proposed approach, the fNIRS signals of finger tapping tasks measured from the left motor cortex are examined. The results show that the KRLS algorithm using the Gaussian kernel yields the best fitting for both ΔHbO (i.e., 87.5%) and ΔHbR (i.e., 85.2%) at q = 15 steps ahead (i.e., 1.63 s ahead at a sampling frequency of 9.19 Hz). This concludes that a neuronal activation can be concluded in about 0.
    fecting the tuning of motivated behaviors. This review analyzes the contribution of the kappa opioid system to the dopaminergic correlates of compulsive behaviors. Copyright © 2020 Escobar, Casanova, Andrés and Fuentealba.Background Obesity is associated with an elevated risk of respiratory infections and inflammatory lung diseases. The objective was to investigate (i) the effects of adipokines (adiponectin (APN), leptin, chemerin, and visfatin) on the production of cytokines by unstimulated and poly(IC)- and TNF-α-activated human primary bronchial epithelial cells (hBECs), (ii) the cells' expression of the APN receptors (AdipoR1 and AdipoR2), and (iii) the cells' production of APN. Methods The hBECs were isolated from patients undergoing surgery for lung carcinoma. The cells were then cultured with human recombinant adipokines in the absence or presence of TNF-α or poly(IC) for 24 h. Supernatant levels of cytokines (IL-6, CCL2, CCL5, CCL20, CXCL1, CXCL8) and APN were measured using ELISAs. The mRNA levels of AdipoR1 and AdipoR2 in hBECs were determined using a real-time quantitative PCR. Results Of the four adipokines tested, only APN significantly influenced the basal production and the TNF-α poly(IC)-induced production of cytokines by hBECs. APN (3-30 µg.ml-1) was associated with greater basal production of IL-6, CCL20, and CXCL8, lower basal production of CCL2 and CXCL1 and no difference in CCL5 production. APN inhibited the poly(IC)-induced production of these five cytokines and the TNF-α-induced production of CCL2 and CXCL1. AdipoR1 and AdipoR2 were both expressed in hBECs. In contrast to human bronchial explants, isolated hBECs did not produce APN. Conclusions The APN concentrations are abnormally low in obese individuals, and this fall may contribute to the susceptibility to viral lung infections and the severity of these infections in obese individuals. Copyright © 2020 Salvator, Grassin-Delyle, Naline, Brollo, Fournier, Couderc and Devillier.The incidences of diabetic mellitus and other metabolic diseases such as hypertension and hyperlipidemia are increasing worldwide; however, the current treatment is not able to control the rapidly increasing trend in diabetes mortality and morbidity. Studies related to the effectiveness of extracts and pure compounds obtained from plants have shown promising responses in preclinical and clinical studies related to these metabolic diseases. Plants belonging to the genus Berberis (Family Berberidaceae) are widely distributed with nearly 550 species worldwide. Extracts and compounds obtained from Berberis species, especially Berberine alkaloid, showed effectiveness in the management of diabetes and other metabolic diseases. Various pharmacological experiments have been performed to evaluate the effects of Berberis extracts, berberine, and its natural and chemically synthesized derivatives against various cell and animal disease models with promising results. Various clinical trials conducted so far also showed preventive effects of Berberis extracts and berberine against metabolic diseases. The present review focuses on i) research updates on traditional uses, ii) phytopharmacology and clinical studies on Berberis species, and iii) active metabolites in the prevention and treatment of diabetes and other metabolic diseases with a detailed mechanism of action. Furthermore, the review critically analyzes current research gaps in the therapeutic use of Berberis species and berberine and provides future recommendations. Copyright © 2020 Belwal, Bisht, Devkota, Ullah, Khan, Pandey, Bhatt and Echeverría.[This corrects the article DOI 10.3389/fnagi.2019.00343.]. Copyright © 2020 Smolek, Cubinkova, Brezovakova, Valachova, Szalay, Zilka and Jadhav.The study investigated the consequences of age-related decline in inhibition processes on intentional switching between bimanual coordination patterns. Fifteen young (24±2.8 years) and 20 older adults (69±5.3 years) performed Stroop tasks and bimanual coordination tasks. Stroop tasks included neutral, congruent, and incongruent conditions. Response time and error rate were measured. Bimanual coordination tasks consisted of performing in-phase (IP) and anti-phase (AP) patterns. Participants were requested to switch as quickly as possible from one pattern to the other, resulting in two different switching directions (AP to IP; IP to AP). Mean and standard deviation (SD) of the continuous relative phase (CRP) were calculated pre- and post-switching for each participant. Total switching time (TST) was measured. The switching phase was also decomposed into reaction time (RT) and reversal time (REvT). Pearson correlation analyses were performed to test for correlations between (i) SD of CRP and response time in Strat inhibition processes are involved in switching between bimanual coordination patterns, at least to trigger the early phase of switching. They also support the hypothesis that inhibition processes are more involved in maintaining the AP pattern and switching to the IP pattern. Finally, age-related changes in switching times seem to be prominently mediated by alterations of inhibition processes. Copyright © 2020 Temprado, Torre, Langeard, Julien-Vintrou, Devillers-Réolon, Sleimen-Malkoun and Berton.An intrinsic problem when using hemodynamic responses for the brain-machine interface is the slow nature of the physiological process. In this paper, a novel method that estimates the oxyhemoglobin changes caused by neuronal activations is proposed and validated. https://www.selleckchem.com/products/methyl-b-cyclodextrin.html In monitoring the time responses of blood-oxygen-level-dependent signals with functional near-infrared spectroscopy (fNIRS), the early trajectories of both oxy- and deoxy-hemoglobins in their phase space are scrutinized. Furthermore, to reduce the detection time, a prediction method based upon a kernel-based recursive least squares (KRLS) algorithm is implemented. In validating the proposed approach, the fNIRS signals of finger tapping tasks measured from the left motor cortex are examined. The results show that the KRLS algorithm using the Gaussian kernel yields the best fitting for both ΔHbO (i.e., 87.5%) and ΔHbR (i.e., 85.2%) at q = 15 steps ahead (i.e., 1.63 s ahead at a sampling frequency of 9.19 Hz). This concludes that a neuronal activation can be concluded in about 0.
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  • ld be concerning. Based on these data, BSFL meal and oil did not affect general health and could be included safely in dog diets.
    The HeartMate 3 left ventricular assist device was first implanted in 2014 and received the Conformité Européenne mark in 2015. Since then, several trials demonstrated its high haemocompatibility associated with good survival and low adverse events rates. Herein, we report our institutional experience with patients supported with HeartMate 3 for 5 years.

    This prospective cohort study included patients receiving a HeartMate 3 implantation in 2014 as part of the HeartMate 3 Conformité Européenne Mark clinical trial. Patients had follow-up visits every 3 months while on left ventricular assist device support, and all patients completed the 5-year follow-up. The primary end point was survival at 5 years. Secondary end points included adverse events, health status and quality of life.

    Eight patients (men 75%) aged 59 years (min-max 52-66 years) were enrolled. At 5 years, survival was 100%. Patients remained on support for a median time of 1825 days (min-max 101-1825 days); 2 patients successfully received cardiac transplants. No right heart failure, haemolysis, pump thrombosis, pump malfunction or neurological events occurred in any patients. A driveline infection was observed in 6 patients (0.25 events/patient-year). Compared to baseline, a significant improvement in quality of life and in New York Heart Association functional class was noted after the implant and for the whole follow-up time. A slight decline in kidney function and in the 6-min walk test results occurred after 3 years.

    This study reports the longest single-centre follow-up of the HeartMate 3, showing excellent haemocompatibility over time with high survival and low complication rates at 5 years.
    This study reports the longest single-centre follow-up of the HeartMate 3, showing excellent haemocompatibility over time with high survival and low complication rates at 5 years.France has been at the epicenter of the worldwide debate about hydroxychloroquine, as the main advocacy for its use to treat COVID-19 comes from a research unit led by Didier Raoult in Marseille. Among a national panel of 2940 general practitioners, we found that physicians in the areas most strongly affected by the epidemic or closest to the epicenter of the controversy reported that the hydroxychloroquine debate had made it difficult for them to deal with patients' treatment requests. Their adherence to official recommendations was also lower. It will be necessary to examine the conditions producing so strong a conflict.As consequence of the various genomic sequencing projects, an increasing volume of biological sequence data is being produced. Although machine learning algorithms have been successfully applied to a large number of genomic sequence-related problems, the results are largely affected by the type and number of features extracted. This effect has motivated new algorithms and pipeline proposals, mainly involving feature extraction problems, in which extracting significant discriminatory information from a biological set is challenging. Considering this, our work proposes a new study of feature extraction approaches based on mathematical features (numerical mapping with Fourier, entropy and complex networks). https://www.selleckchem.com/products/pf-06463922.html As a case study, we analyze long non-coding RNA sequences. Moreover, we separated this work into three studies. First, we assessed our proposal with the most addressed problem in our review, e.g. lncRNA and mRNA; second, we also validate the mathematical features in different classification problems, to predict the class of lncRNA, e.g. circular RNAs sequences; third, we analyze its robustness in scenarios with imbalanced data. The experimental results demonstrated three main contributions first, an in-depth study of several mathematical features; second, a new feature extraction pipeline; and third, its high performance and robustness for distinct RNA sequence classification. Availability https//github.com/Bonidia/FeatureExtraction_BiologicalSequences.
    The emergence of antibiotic-resistant species calls for fast and reliable phenotypic susceptibility testing to adapt clinical management as fast as possible.

    We assessed the real-life performance of EUCAST rapid antimicrobial susceptibility testing (RAST) and analysed its impact on patient management.

    RAST was performed on clinical blood cultures containing Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa or Acinetobacter baumannii complex. Categorical agreement with VITEK2 was analysed. A pre-post quasi-experimental observational study was designed to compare antibiotic treatment in sepsis patients in the RAST patient group (n = 51) and a historical control cohort (n = 54).

    In total, 436 isolates, corresponding to 2314 disc diameters, were measured; 18.4% of these measurements were in the area of technical uncertainty. For the 81.6% categorical results, which could be compared, 94.7% were in agreement, whereas 5.3% of the results were not. In the RAST group, optimal therapy was initiat.A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was 'Is left ventricular superior to right ventricular pacing in children with congenital or postoperative complete heart block?' Altogether, 19 papers were found using the reported search, of which 9 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Two large multicentric showed that site of pacing was the major determinant of left ventricular (LV) function with LV pacing being superior to RV pacing, though the number of patients paced via LV was lesser in comparison to right ventricular (RV). There were 2 prospective, 2 retrospective and 1 cross-sectional studies with fewer patients that demonstrated superiority of LV over RV pacing in preserving LV function. Only 1 small-scale retrospective study showed similar results of LV and RV pacing on LV function.
    ld be concerning. Based on these data, BSFL meal and oil did not affect general health and could be included safely in dog diets. The HeartMate 3 left ventricular assist device was first implanted in 2014 and received the Conformité Européenne mark in 2015. Since then, several trials demonstrated its high haemocompatibility associated with good survival and low adverse events rates. Herein, we report our institutional experience with patients supported with HeartMate 3 for 5 years. This prospective cohort study included patients receiving a HeartMate 3 implantation in 2014 as part of the HeartMate 3 Conformité Européenne Mark clinical trial. Patients had follow-up visits every 3 months while on left ventricular assist device support, and all patients completed the 5-year follow-up. The primary end point was survival at 5 years. Secondary end points included adverse events, health status and quality of life. Eight patients (men 75%) aged 59 years (min-max 52-66 years) were enrolled. At 5 years, survival was 100%. Patients remained on support for a median time of 1825 days (min-max 101-1825 days); 2 patients successfully received cardiac transplants. No right heart failure, haemolysis, pump thrombosis, pump malfunction or neurological events occurred in any patients. A driveline infection was observed in 6 patients (0.25 events/patient-year). Compared to baseline, a significant improvement in quality of life and in New York Heart Association functional class was noted after the implant and for the whole follow-up time. A slight decline in kidney function and in the 6-min walk test results occurred after 3 years. This study reports the longest single-centre follow-up of the HeartMate 3, showing excellent haemocompatibility over time with high survival and low complication rates at 5 years. This study reports the longest single-centre follow-up of the HeartMate 3, showing excellent haemocompatibility over time with high survival and low complication rates at 5 years.France has been at the epicenter of the worldwide debate about hydroxychloroquine, as the main advocacy for its use to treat COVID-19 comes from a research unit led by Didier Raoult in Marseille. Among a national panel of 2940 general practitioners, we found that physicians in the areas most strongly affected by the epidemic or closest to the epicenter of the controversy reported that the hydroxychloroquine debate had made it difficult for them to deal with patients' treatment requests. Their adherence to official recommendations was also lower. It will be necessary to examine the conditions producing so strong a conflict.As consequence of the various genomic sequencing projects, an increasing volume of biological sequence data is being produced. Although machine learning algorithms have been successfully applied to a large number of genomic sequence-related problems, the results are largely affected by the type and number of features extracted. This effect has motivated new algorithms and pipeline proposals, mainly involving feature extraction problems, in which extracting significant discriminatory information from a biological set is challenging. Considering this, our work proposes a new study of feature extraction approaches based on mathematical features (numerical mapping with Fourier, entropy and complex networks). https://www.selleckchem.com/products/pf-06463922.html As a case study, we analyze long non-coding RNA sequences. Moreover, we separated this work into three studies. First, we assessed our proposal with the most addressed problem in our review, e.g. lncRNA and mRNA; second, we also validate the mathematical features in different classification problems, to predict the class of lncRNA, e.g. circular RNAs sequences; third, we analyze its robustness in scenarios with imbalanced data. The experimental results demonstrated three main contributions first, an in-depth study of several mathematical features; second, a new feature extraction pipeline; and third, its high performance and robustness for distinct RNA sequence classification. Availability https//github.com/Bonidia/FeatureExtraction_BiologicalSequences. The emergence of antibiotic-resistant species calls for fast and reliable phenotypic susceptibility testing to adapt clinical management as fast as possible. We assessed the real-life performance of EUCAST rapid antimicrobial susceptibility testing (RAST) and analysed its impact on patient management. RAST was performed on clinical blood cultures containing Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa or Acinetobacter baumannii complex. Categorical agreement with VITEK2 was analysed. A pre-post quasi-experimental observational study was designed to compare antibiotic treatment in sepsis patients in the RAST patient group (n = 51) and a historical control cohort (n = 54). In total, 436 isolates, corresponding to 2314 disc diameters, were measured; 18.4% of these measurements were in the area of technical uncertainty. For the 81.6% categorical results, which could be compared, 94.7% were in agreement, whereas 5.3% of the results were not. In the RAST group, optimal therapy was initiat.A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was 'Is left ventricular superior to right ventricular pacing in children with congenital or postoperative complete heart block?' Altogether, 19 papers were found using the reported search, of which 9 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Two large multicentric showed that site of pacing was the major determinant of left ventricular (LV) function with LV pacing being superior to RV pacing, though the number of patients paced via LV was lesser in comparison to right ventricular (RV). There were 2 prospective, 2 retrospective and 1 cross-sectional studies with fewer patients that demonstrated superiority of LV over RV pacing in preserving LV function. Only 1 small-scale retrospective study showed similar results of LV and RV pacing on LV function.
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  • However, DL-PCBs 77, 81 and 126 were all negative in both cell lines. In a human hepatoma (C3A) cell line, PCB 105 and 118 induced micronuclei marginally, while with ethanol pretreatment (to stabilize CYP2E1) both compounds induced micronuclei efficiently, and co-exposure to trans-1,2-dichloroethylene (a selective CYP2E1 inhibitor) led to clearly negative results with both compounds. Finally, both PCB 105 and 118 induced PIG-A gene mutations in C3A cells, which was blocked by trans-1,2-dichloroethylene. In summary, in silico and experimental results consistently suggest that DL- PCBs 105 and 118 may be activated by human CYP2E1 for mutagenic activities. Previous studies have focused on the impact of visibility level on drivers' behavior and their safety in foggy weather. However, other important environmental factors such as road alignment have not been considered. This paper aims to propose a methodology in investigating rear-end collision avoidance behavior under varied foggy conditions, with focusing on changes in visibility and road alignment in this study. A driving simulator experiment with a mixed 2 × 4 × 6 factor design was conducted using an advanced high-fidelity driving simulator. The design matrix includes two safety-critical conditions, four visibility conditions, and six road alignment situations (in terms of the road curve and slope). Behavior variables from different dimensions were identified and compared under varied conditions. To estimate the safety of drivers, a time-based measurement, speed reduction time, is selected among the variables as a measure of safety. The survival analysis approach was introduced to model the relationship between environmental factors and driver safety, using speed reduction time as the survival time. Both the Kaplan-Meier method and the COX model were applied and compared. Results generally suggest that reduced visibility leads to more dangerous rear-end collision avoidance behavior from different aspects. Though findings are mixed regarding the road alignment, the impact of the road alignment was found to be significant. Interestingly, conditions of downward slope were found to be safer. Overall, the COX model outperformed the Kaplan-Meier method in understanding the impact of environmental factors, and it can be applied to investigate other contributing factors for freeway safety under foggy weather conditions. Within the last decades the incidence of workspace injuries and fatalities in the UK construction industry has declined markedly following the developments in occupational health and safety (OHS) management systems. However, safety statistics have reached a plateau and actions for further improvement of OHS management systems are called for. OHS is a form of organizational expertise that has both tacit and explicit dimensions and is situated in the ongoing practices. There is a need for institutionalization and for the transfer of knowledge across and along construction supply chains to reduce OHS risks and facilitate cultural change. The focus of this article is the factors that facilitate OHS knowledge transfer in and between organizations involved in construction projects. An interpretative methodology is used in this research to embrace tacit aspects of knowledge transfer and application. Thematic analysis is supported by a cognitive mapping technique that allows understanding of interrelationships among the concepts expressed by the respondents. This paper demonstrates inconsistency in OHS practices in construction organizations and highlights the importance of cultivating a positive safety culture to encourage transfer of lessons learnt from good practices, incidents, near misses and failures between projects, from projects to programmes and across supply chains. Governmental health and safety regulations, norms and guidelines do not include all possible safety issues specific to different working environments and tied to work contexts. https://www.selleckchem.com/products/cytosporone-b.html The OHS system should encourage employees to report near misses, incidents and failures in a 'no-blame' context and to take appropriate actions. This research provides foundation for construction project practitioners to adopt more socially oriented approaches towards promoting learning-rich organizational contexts to overcome variation in the OHS and move beyond the current plateau reached in safety statistics. BACKGROUND Several factors may influence the decision to drink-drive (DD) in young drivers, such as the amount of alcohol consumed, exposure to an in-vehicle alcohol feedback device, and subjective responses to alcohol. Understanding of their influence on DD is lacking and may be key for targeted intervention. This randomized controlled, double-blinded, driving simulation experiment tested three main hypotheses; young drivers are more likely to engage in DD with i) lower alcohol dose; ii) lack of exposure to an in-vehicle alcohol feedback (FB) device; and iii) lower subjective responses to alcohol intoxication (SR). Interactions between the decision to DD and SR, FB and sex were also explored. METHODS Males (n = 80) and females (n = 80) aged 20-24 years old were randomly assigned to two conditions i) alcohol dose (0.45 g/kg or 0.65 g/kg); and ii) exposure to an in-vehicle alcohol feedback device (no or yes). Assessment of participants' SR following alcohol intake was based upon two measures i) subjective intoect = .054, p  less then  .001, 95 % CI = .026-.083). CONCLUSIONS Lower SR was found to be associated with a greater likelihood of the decision to DD in young drivers, while exposure to an in-vehicle FB device had no effect on DD. Importantly, FB exposure appeared to disrupt the relationship between lower SR and the decision to DD, signaling that FB may be selectively effective for young drivers possessing lower SR. Future studies are needed to clarify whether FB technology, and other interventions, can be targeted to deter DD in the young drivers most likely to benefit. OBJECTIVE Identifiable individual-level driver licensing and motor vehicle crash data are essential to advancing transportation safety research. However, epidemiologic studies using such data are rare, which may reflect their inaccessibility. We conducted a legal mapping study to evaluate US state laws regulating access to driver licensing and motor vehicle crash data for use in scientific research. METHODS Legal statutes regulating the release of driver licensing and motor vehicle crash data for all 50 US states and the District of Columbia (D.C.) were retrieved. Legal text was evaluated to determine whether these jurisdictions authorize release of identifiable individual-level licensing and crash data for use in non-governmental research. RESULTS Thirty-six states and D.C. explicitly authorize release of identifiable individual-level licensing data to researchers. Only five states and D.C. authorize release of identifiable individual-level crash records. No states explicitly prohibit the release of individual-level data about licensing records and only three states prohibit release of individual-level crash record data, meaning that in many states it is ambiguous whether and when releasing such data to researchers is permitted.
    However, DL-PCBs 77, 81 and 126 were all negative in both cell lines. In a human hepatoma (C3A) cell line, PCB 105 and 118 induced micronuclei marginally, while with ethanol pretreatment (to stabilize CYP2E1) both compounds induced micronuclei efficiently, and co-exposure to trans-1,2-dichloroethylene (a selective CYP2E1 inhibitor) led to clearly negative results with both compounds. Finally, both PCB 105 and 118 induced PIG-A gene mutations in C3A cells, which was blocked by trans-1,2-dichloroethylene. In summary, in silico and experimental results consistently suggest that DL- PCBs 105 and 118 may be activated by human CYP2E1 for mutagenic activities. Previous studies have focused on the impact of visibility level on drivers' behavior and their safety in foggy weather. However, other important environmental factors such as road alignment have not been considered. This paper aims to propose a methodology in investigating rear-end collision avoidance behavior under varied foggy conditions, with focusing on changes in visibility and road alignment in this study. A driving simulator experiment with a mixed 2 × 4 × 6 factor design was conducted using an advanced high-fidelity driving simulator. The design matrix includes two safety-critical conditions, four visibility conditions, and six road alignment situations (in terms of the road curve and slope). Behavior variables from different dimensions were identified and compared under varied conditions. To estimate the safety of drivers, a time-based measurement, speed reduction time, is selected among the variables as a measure of safety. The survival analysis approach was introduced to model the relationship between environmental factors and driver safety, using speed reduction time as the survival time. Both the Kaplan-Meier method and the COX model were applied and compared. Results generally suggest that reduced visibility leads to more dangerous rear-end collision avoidance behavior from different aspects. Though findings are mixed regarding the road alignment, the impact of the road alignment was found to be significant. Interestingly, conditions of downward slope were found to be safer. Overall, the COX model outperformed the Kaplan-Meier method in understanding the impact of environmental factors, and it can be applied to investigate other contributing factors for freeway safety under foggy weather conditions. Within the last decades the incidence of workspace injuries and fatalities in the UK construction industry has declined markedly following the developments in occupational health and safety (OHS) management systems. However, safety statistics have reached a plateau and actions for further improvement of OHS management systems are called for. OHS is a form of organizational expertise that has both tacit and explicit dimensions and is situated in the ongoing practices. There is a need for institutionalization and for the transfer of knowledge across and along construction supply chains to reduce OHS risks and facilitate cultural change. The focus of this article is the factors that facilitate OHS knowledge transfer in and between organizations involved in construction projects. An interpretative methodology is used in this research to embrace tacit aspects of knowledge transfer and application. Thematic analysis is supported by a cognitive mapping technique that allows understanding of interrelationships among the concepts expressed by the respondents. This paper demonstrates inconsistency in OHS practices in construction organizations and highlights the importance of cultivating a positive safety culture to encourage transfer of lessons learnt from good practices, incidents, near misses and failures between projects, from projects to programmes and across supply chains. Governmental health and safety regulations, norms and guidelines do not include all possible safety issues specific to different working environments and tied to work contexts. https://www.selleckchem.com/products/cytosporone-b.html The OHS system should encourage employees to report near misses, incidents and failures in a 'no-blame' context and to take appropriate actions. This research provides foundation for construction project practitioners to adopt more socially oriented approaches towards promoting learning-rich organizational contexts to overcome variation in the OHS and move beyond the current plateau reached in safety statistics. BACKGROUND Several factors may influence the decision to drink-drive (DD) in young drivers, such as the amount of alcohol consumed, exposure to an in-vehicle alcohol feedback device, and subjective responses to alcohol. Understanding of their influence on DD is lacking and may be key for targeted intervention. This randomized controlled, double-blinded, driving simulation experiment tested three main hypotheses; young drivers are more likely to engage in DD with i) lower alcohol dose; ii) lack of exposure to an in-vehicle alcohol feedback (FB) device; and iii) lower subjective responses to alcohol intoxication (SR). Interactions between the decision to DD and SR, FB and sex were also explored. METHODS Males (n = 80) and females (n = 80) aged 20-24 years old were randomly assigned to two conditions i) alcohol dose (0.45 g/kg or 0.65 g/kg); and ii) exposure to an in-vehicle alcohol feedback device (no or yes). Assessment of participants' SR following alcohol intake was based upon two measures i) subjective intoect = .054, p  less then  .001, 95 % CI = .026-.083). CONCLUSIONS Lower SR was found to be associated with a greater likelihood of the decision to DD in young drivers, while exposure to an in-vehicle FB device had no effect on DD. Importantly, FB exposure appeared to disrupt the relationship between lower SR and the decision to DD, signaling that FB may be selectively effective for young drivers possessing lower SR. Future studies are needed to clarify whether FB technology, and other interventions, can be targeted to deter DD in the young drivers most likely to benefit. OBJECTIVE Identifiable individual-level driver licensing and motor vehicle crash data are essential to advancing transportation safety research. However, epidemiologic studies using such data are rare, which may reflect their inaccessibility. We conducted a legal mapping study to evaluate US state laws regulating access to driver licensing and motor vehicle crash data for use in scientific research. METHODS Legal statutes regulating the release of driver licensing and motor vehicle crash data for all 50 US states and the District of Columbia (D.C.) were retrieved. Legal text was evaluated to determine whether these jurisdictions authorize release of identifiable individual-level licensing and crash data for use in non-governmental research. RESULTS Thirty-six states and D.C. explicitly authorize release of identifiable individual-level licensing data to researchers. Only five states and D.C. authorize release of identifiable individual-level crash records. No states explicitly prohibit the release of individual-level data about licensing records and only three states prohibit release of individual-level crash record data, meaning that in many states it is ambiguous whether and when releasing such data to researchers is permitted.
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  • 3% and superior bending durability of ≈98.5% after 1000 cycles of harsh bending tests are achieved. The nanoscale pores and the capability of the porous structure to impede crack generation and propagation enable the nanoporous Au electrode to be recycled and result in excellent bending durability. © 2020 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.Piezoelectric polymers are well-recognized to hold great promise for a wide range of flexible, wearable, and biocompatible applications. Among the known piezoelectric polymers, ferroelectric polymers represented by poly(vinylidene fluoride) and its copolymer poly(vinylidene fluoride-co-trifluoroethylene) possess the best piezoelectric coefficients. https://www.selleckchem.com/products/su056.html However, the physical origin of negative longitudinal piezoelectric coefficients occurring in the polymers remains elusive. To address this long-standing challenge, several theoretical models proposed over the past decades, which are controversial in nature, have been revisited and reviewed. It is concluded that negative longitudinal piezoelectric coefficients arise from the negative longitudinal electrostriction in the crystalline domain of the polymers, independent of amorphous and crystalline-amorphous interfacial regions. The crystalline origin of piezoelectricity offers unprecedented opportunities to improve electromechanical properties of polymers via structural engineering, i.e., design of morphotropic phase boundaries in ferroelectric polymers. © 2020 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.Visible light-driving syntheses have emerged as a powerful tool for organic synthesis and for the preparation of macromolecules under mild and environmentally benign conditions. However, precious but nonreusable photosensitizers or photocatalysts are often required to activate the reaction, limiting its practicality. Here, it is reported that poly(1,4-diphenylbutadiyne) (PDPB) nanofibers exhibit remarkable activity in driving the living free radical polymerization under visible light. Moreover, PDPB nanofibers are very stable under irradiation of visible light and can be reused without appreciable loss of activity even after repeated cycling. The nanofiber will be a promising photocatalyst with excellent reusability and stability for the reactions driven by visible light. © 2020 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.As the most versatile and promising cell source, stem cells have been studied in regenerative medicine for two decades. Currently available culturing techniques utilize a 2D or 3D microenvironment for supporting the growth and proliferation of stem cells. However, these culture systems fail to fully reflect the supportive biological environment in which stem cells reside in vivo, which contain dynamic biophysical growth cues. Herein, a 4D programmable culture substrate with a self-morphing capability is presented as a means to enhance dynamic cell growth and induce differentiation of stem cells. To function as a model system, a 4D neural culture substrate is fabricated using a combination of printing and imprinting techniques keyed to the different biological features of neural stem cells (NSCs) at different differentiation stages. Results show the 4D culture substrate demonstrates a time-dependent self-morphing process that plays an essential role in regulating NSC behaviors in a spatiotemporal manner and enhances neural differentiation of NSCs along with significant axonal alignment. This study of a customized, dynamic substrate revolutionizes current stem cell therapies, and can further have a far-reaching impact on improving tissue regeneration and mimicking specific disease progression, as well as other impacts on materials and life science research. © 2020 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.Extracellular vesicles (EVs) are endogenous membrane-derived vesicles that shuttle bioactive molecules between glia and neurons, thereby promoting neuronal survival and plasticity in the central nervous system (CNS) and contributing to neurodegenerative conditions. Although EVs hold great potential as CNS theranostic nanocarriers, the specific molecular factors that regulate neuronal EV uptake and release are currently unknown. A combination of patch-clamp electrophysiology and pH-sensitive dye imaging is used to examine stimulus-evoked EV release in individual neurons in real time. Whereas spontaneous electrical activity and the application of a high-frequency stimulus induce a slow and prolonged fusion of multivesicular bodies (MVBs) with the plasma membrane (PM) in a subset of cells, the neurotrophic factor basic fibroblast growth factor (bFGF) greatly increases the rate of stimulus-evoked MVB-PM fusion events and, consequently, the abundance of EVs in the culture medium. Proteomic analysis of neuronal EVs demonstrates bFGF increases the abundance of the v-SNARE vesicle-associated membrane protein 3 (VAMP3, cellubrevin) on EVs. Conversely, knocking-down VAMP3 in cultured neurons attenuates the effect of bFGF on EV release. The results determine the temporal characteristics of MVB-PM fusion in hippocampal neurons and reveal a new function for bFGF signaling in controlling neuronal EV release. © 2020 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.Controlling the growth behavior of organic semiconductors (OSCs) is essential because it determines their optoelectronic properties. In order to accomplish this, graphene templates with electronic-state tunability are used to affect the growth of OSCs by controlling the van der Waals interaction between OSC ad-molecules and graphene. However, in many graphene-molecule systems, the charge transfer between an ad-molecule and a graphene template causes another important interaction. This charge-transfer-induced interaction is never considered in the growth scheme of OSCs. Here, the effects of charge transfer on the formation of graphene-OSC heterostructures are investigated, using fullerene (C60) as a model compound. By in situ electrical doping of a graphene template to suppress the charge transfer between C60 ad-molecules and graphene, the layer-by-layer growth of a C60 film on graphene can be achieved. Under this condition, the graphene-C60 interface is free of Fermi-level pinning; thus, barristors fabricated on the graphene-C60 interface show a nearly ideal Schottky-Mott limit with efficient modulation of the charge-injection barrier.
    3% and superior bending durability of ≈98.5% after 1000 cycles of harsh bending tests are achieved. The nanoscale pores and the capability of the porous structure to impede crack generation and propagation enable the nanoporous Au electrode to be recycled and result in excellent bending durability. © 2020 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.Piezoelectric polymers are well-recognized to hold great promise for a wide range of flexible, wearable, and biocompatible applications. Among the known piezoelectric polymers, ferroelectric polymers represented by poly(vinylidene fluoride) and its copolymer poly(vinylidene fluoride-co-trifluoroethylene) possess the best piezoelectric coefficients. https://www.selleckchem.com/products/su056.html However, the physical origin of negative longitudinal piezoelectric coefficients occurring in the polymers remains elusive. To address this long-standing challenge, several theoretical models proposed over the past decades, which are controversial in nature, have been revisited and reviewed. It is concluded that negative longitudinal piezoelectric coefficients arise from the negative longitudinal electrostriction in the crystalline domain of the polymers, independent of amorphous and crystalline-amorphous interfacial regions. The crystalline origin of piezoelectricity offers unprecedented opportunities to improve electromechanical properties of polymers via structural engineering, i.e., design of morphotropic phase boundaries in ferroelectric polymers. © 2020 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.Visible light-driving syntheses have emerged as a powerful tool for organic synthesis and for the preparation of macromolecules under mild and environmentally benign conditions. However, precious but nonreusable photosensitizers or photocatalysts are often required to activate the reaction, limiting its practicality. Here, it is reported that poly(1,4-diphenylbutadiyne) (PDPB) nanofibers exhibit remarkable activity in driving the living free radical polymerization under visible light. Moreover, PDPB nanofibers are very stable under irradiation of visible light and can be reused without appreciable loss of activity even after repeated cycling. The nanofiber will be a promising photocatalyst with excellent reusability and stability for the reactions driven by visible light. © 2020 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.As the most versatile and promising cell source, stem cells have been studied in regenerative medicine for two decades. Currently available culturing techniques utilize a 2D or 3D microenvironment for supporting the growth and proliferation of stem cells. However, these culture systems fail to fully reflect the supportive biological environment in which stem cells reside in vivo, which contain dynamic biophysical growth cues. Herein, a 4D programmable culture substrate with a self-morphing capability is presented as a means to enhance dynamic cell growth and induce differentiation of stem cells. To function as a model system, a 4D neural culture substrate is fabricated using a combination of printing and imprinting techniques keyed to the different biological features of neural stem cells (NSCs) at different differentiation stages. Results show the 4D culture substrate demonstrates a time-dependent self-morphing process that plays an essential role in regulating NSC behaviors in a spatiotemporal manner and enhances neural differentiation of NSCs along with significant axonal alignment. This study of a customized, dynamic substrate revolutionizes current stem cell therapies, and can further have a far-reaching impact on improving tissue regeneration and mimicking specific disease progression, as well as other impacts on materials and life science research. © 2020 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.Extracellular vesicles (EVs) are endogenous membrane-derived vesicles that shuttle bioactive molecules between glia and neurons, thereby promoting neuronal survival and plasticity in the central nervous system (CNS) and contributing to neurodegenerative conditions. Although EVs hold great potential as CNS theranostic nanocarriers, the specific molecular factors that regulate neuronal EV uptake and release are currently unknown. A combination of patch-clamp electrophysiology and pH-sensitive dye imaging is used to examine stimulus-evoked EV release in individual neurons in real time. Whereas spontaneous electrical activity and the application of a high-frequency stimulus induce a slow and prolonged fusion of multivesicular bodies (MVBs) with the plasma membrane (PM) in a subset of cells, the neurotrophic factor basic fibroblast growth factor (bFGF) greatly increases the rate of stimulus-evoked MVB-PM fusion events and, consequently, the abundance of EVs in the culture medium. Proteomic analysis of neuronal EVs demonstrates bFGF increases the abundance of the v-SNARE vesicle-associated membrane protein 3 (VAMP3, cellubrevin) on EVs. Conversely, knocking-down VAMP3 in cultured neurons attenuates the effect of bFGF on EV release. The results determine the temporal characteristics of MVB-PM fusion in hippocampal neurons and reveal a new function for bFGF signaling in controlling neuronal EV release. © 2020 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.Controlling the growth behavior of organic semiconductors (OSCs) is essential because it determines their optoelectronic properties. In order to accomplish this, graphene templates with electronic-state tunability are used to affect the growth of OSCs by controlling the van der Waals interaction between OSC ad-molecules and graphene. However, in many graphene-molecule systems, the charge transfer between an ad-molecule and a graphene template causes another important interaction. This charge-transfer-induced interaction is never considered in the growth scheme of OSCs. Here, the effects of charge transfer on the formation of graphene-OSC heterostructures are investigated, using fullerene (C60) as a model compound. By in situ electrical doping of a graphene template to suppress the charge transfer between C60 ad-molecules and graphene, the layer-by-layer growth of a C60 film on graphene can be achieved. Under this condition, the graphene-C60 interface is free of Fermi-level pinning; thus, barristors fabricated on the graphene-C60 interface show a nearly ideal Schottky-Mott limit with efficient modulation of the charge-injection barrier.
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  • conclusion, one-fourth of SARS-CoV-2 infections are remained asymptomatic throughout the course infection. Scale-up of testing, which targeting high risk populations is recommended to tackle the pandemic.In this study, a key issue to be addressed is the safe disposal of hybridoma instability. Hybridoma technology was used to produce anti-O. viverrini monoclonal antibody. Previous studies have shown that antibody production via antibody phage display can sustain the hybridoma technique. This paper presents the utility of antibody phage display technology for producing the phage displayed KKU505 Fab fragment and using experiments in concomitant with molecular simulation for characterization. The phage displayed KKU505 Fab fragment and characterization were successfully carried out. The KKU505 hybridoma cell line producing anti-O. viverrini antibody predicted to bind to myosin was used to synthesize cDNA so as to amplify the heavy chain and the light chain sequences. The KKU505 displayed phage was constructed and characterized by a molecular modeling in which the KKU505 Fab fragment and -O. viverrini myosin head were docked computationally and it is assumed that the Fab fragment was specific to -O. viverrini on the basis of mass spectrometry and Western blot. This complex interaction was confirmed by molecular simulation. Furthermore, the KKU505 displayed phage was validated using indirect enzyme-linked immunosorbent assays (ELISA) and immunohistochemistry. It is worthy to note that ELISA and immunohistochemistry results confirmed that the Fab fragment was specific to the -O. viverrini antigen. Results indicated that the approach presented herein can generate anti-O. viverrini antibody via the phage display technology. This study integrates the use of phage display technology together with molecular simulation for further development of monoclonal antibody production. Furthermore, the presented work has profound implications for antibody production, particularly by solving the problem of hybridoma stability issues.Neonatal hypothermia is a great concern with near epidemic levels globally. In Kenya, its prevalence is as high as 87% with limited local data on the associated factors such as adherence to warm chain guidelines as recommended by the World Health Organisation (WHO) is limited. This study aimed to determine the prevalence of hypothermia and level of adherence to the WHO thermal care guidelines among newborns admitted at Moi Teaching and Referral Hospital (MTRH). It adopted a prospective study design of following up neonates for the first 24 hours of admission to the MTRH newborn unit. Thermometry, interview of mothers and observation of thermal care practices was done. Descriptive and inferential statistical techniques were adopted. Specifically, Pearson's chi-square test of associations between predictors of neonatal hypothermia and management outcomes was conducted with their corresponding risk estimates at 95% confidence interval. Among the 372 participants, 64.5% (n = 240) were born at MTRH, 47.6% (177) were preterm and 53.2% (198) had birth weights below 2500 grams. Admission hypothermia was noted among 73.7% (274) and 13% (49) died on the first day of admission. Only 7.8% (29) newborns accessed optimal thermal care. Prematurity, day one mortality and adherence to the warm chain were significantly (p less then 0.001) associated with admission hypothermia. https://www.selleckchem.com/products/JNJ-26481585.html Inappropriate thermal appliance, inadequate clothing and late breastfeeding significantly increased the risk of neonatal hypothermia. Absence of admission hypothermia increased the likelihood of neonatal survival more than twenty-fold (AOR = 20.91, 95% CI 2.15-153.62). Three out four neonates enrolled had admission hypothermia which was significantly associated with prematurity, lack of adherence to warm chain and increased risk of neonatal mortality on the first day of life. There was low adherence to the WHO thermal care guidelines. This should be optimized among preterm neonates to improve likelihood of survival.
    This study aimed to capture the acceptability prior to, during and after the implementation of the first year of MDA rounds conducted under the Magude project, a malaria elimination project in southern Mozambique.

    This was a mixed-methods study, consisting of focus group discussions (FGDs) prior to the implementation of MDA rounds (September 2015), non-participant observations (NPOs) conducted during the MDA rounds (November 2015 -beginning of February 2016), and semi-structured interviews (SSIs) after the second round (end of February 2016). Community leaders, women in reproductive age, general members of the community, traditional healers and health professionals were recruited to capture the opinions of all representing key members of the community. A generic outline of nodes and codes was designed to analyze FGDs and SSI separately. Qualitative and quantitative NPO information was analyzed following a content analysis approach.

    222 participants took part in the FGDs (n = 154), and SSIs (n = 68); andn of antimalarial MDAs in southern Mozambique should focus on locally adapted strategies that engage the community to minimize absenteeism and refusals to the intervention.
    Magude's community generally accepted the first and second antimalarial MDA rounds, and the procedures associated to the intervention. Future implementation of antimalarial MDAs in southern Mozambique should focus on locally adapted strategies that engage the community to minimize absenteeism and refusals to the intervention.**** pain and intervertebral disc degeneration are prevalent, costly, and widely treated by manual therapies, yet the underlying causes of these diseases are indeterminate as are the scientific bases for such treatments. The present studies characterize the effects of repetitive in vivo manual loads on porcine intervertebral disc cell metabolism using RNA deep sequencing. A single session of repetitive manual loading applied to the lumbar spine induced both up- and down-regulation of a variety of genes transcribed by cells in the ventral annuli fibrosi. The effect of manual therapy at the level of loading was greater than at a level distant to the applied load. Gene ontology and molecular pathway analyses categorized biological, molecular, and cellular functions influenced by repetitive manual loading, with over-representation of membrane, transmembrane, and pericellular activities. Weighted Gene Co-expression Network Analysis discerned enrichment in genes in pathways of inflammation and skeletogenesis. The present studies support previous findings of intervertebral disc cell mechanotransduction, and are the first to report comprehensively on the repertoire of gene targets influenced by mechanical loads associated with manual therapy interventions.
    conclusion, one-fourth of SARS-CoV-2 infections are remained asymptomatic throughout the course infection. Scale-up of testing, which targeting high risk populations is recommended to tackle the pandemic.In this study, a key issue to be addressed is the safe disposal of hybridoma instability. Hybridoma technology was used to produce anti-O. viverrini monoclonal antibody. Previous studies have shown that antibody production via antibody phage display can sustain the hybridoma technique. This paper presents the utility of antibody phage display technology for producing the phage displayed KKU505 Fab fragment and using experiments in concomitant with molecular simulation for characterization. The phage displayed KKU505 Fab fragment and characterization were successfully carried out. The KKU505 hybridoma cell line producing anti-O. viverrini antibody predicted to bind to myosin was used to synthesize cDNA so as to amplify the heavy chain and the light chain sequences. The KKU505 displayed phage was constructed and characterized by a molecular modeling in which the KKU505 Fab fragment and -O. viverrini myosin head were docked computationally and it is assumed that the Fab fragment was specific to -O. viverrini on the basis of mass spectrometry and Western blot. This complex interaction was confirmed by molecular simulation. Furthermore, the KKU505 displayed phage was validated using indirect enzyme-linked immunosorbent assays (ELISA) and immunohistochemistry. It is worthy to note that ELISA and immunohistochemistry results confirmed that the Fab fragment was specific to the -O. viverrini antigen. Results indicated that the approach presented herein can generate anti-O. viverrini antibody via the phage display technology. This study integrates the use of phage display technology together with molecular simulation for further development of monoclonal antibody production. Furthermore, the presented work has profound implications for antibody production, particularly by solving the problem of hybridoma stability issues.Neonatal hypothermia is a great concern with near epidemic levels globally. In Kenya, its prevalence is as high as 87% with limited local data on the associated factors such as adherence to warm chain guidelines as recommended by the World Health Organisation (WHO) is limited. This study aimed to determine the prevalence of hypothermia and level of adherence to the WHO thermal care guidelines among newborns admitted at Moi Teaching and Referral Hospital (MTRH). It adopted a prospective study design of following up neonates for the first 24 hours of admission to the MTRH newborn unit. Thermometry, interview of mothers and observation of thermal care practices was done. Descriptive and inferential statistical techniques were adopted. Specifically, Pearson's chi-square test of associations between predictors of neonatal hypothermia and management outcomes was conducted with their corresponding risk estimates at 95% confidence interval. Among the 372 participants, 64.5% (n = 240) were born at MTRH, 47.6% (177) were preterm and 53.2% (198) had birth weights below 2500 grams. Admission hypothermia was noted among 73.7% (274) and 13% (49) died on the first day of admission. Only 7.8% (29) newborns accessed optimal thermal care. Prematurity, day one mortality and adherence to the warm chain were significantly (p less then 0.001) associated with admission hypothermia. https://www.selleckchem.com/products/JNJ-26481585.html Inappropriate thermal appliance, inadequate clothing and late breastfeeding significantly increased the risk of neonatal hypothermia. Absence of admission hypothermia increased the likelihood of neonatal survival more than twenty-fold (AOR = 20.91, 95% CI 2.15-153.62). Three out four neonates enrolled had admission hypothermia which was significantly associated with prematurity, lack of adherence to warm chain and increased risk of neonatal mortality on the first day of life. There was low adherence to the WHO thermal care guidelines. This should be optimized among preterm neonates to improve likelihood of survival. This study aimed to capture the acceptability prior to, during and after the implementation of the first year of MDA rounds conducted under the Magude project, a malaria elimination project in southern Mozambique. This was a mixed-methods study, consisting of focus group discussions (FGDs) prior to the implementation of MDA rounds (September 2015), non-participant observations (NPOs) conducted during the MDA rounds (November 2015 -beginning of February 2016), and semi-structured interviews (SSIs) after the second round (end of February 2016). Community leaders, women in reproductive age, general members of the community, traditional healers and health professionals were recruited to capture the opinions of all representing key members of the community. A generic outline of nodes and codes was designed to analyze FGDs and SSI separately. Qualitative and quantitative NPO information was analyzed following a content analysis approach. 222 participants took part in the FGDs (n = 154), and SSIs (n = 68); andn of antimalarial MDAs in southern Mozambique should focus on locally adapted strategies that engage the community to minimize absenteeism and refusals to the intervention. Magude's community generally accepted the first and second antimalarial MDA rounds, and the procedures associated to the intervention. Future implementation of antimalarial MDAs in southern Mozambique should focus on locally adapted strategies that engage the community to minimize absenteeism and refusals to the intervention.Back pain and intervertebral disc degeneration are prevalent, costly, and widely treated by manual therapies, yet the underlying causes of these diseases are indeterminate as are the scientific bases for such treatments. The present studies characterize the effects of repetitive in vivo manual loads on porcine intervertebral disc cell metabolism using RNA deep sequencing. A single session of repetitive manual loading applied to the lumbar spine induced both up- and down-regulation of a variety of genes transcribed by cells in the ventral annuli fibrosi. The effect of manual therapy at the level of loading was greater than at a level distant to the applied load. Gene ontology and molecular pathway analyses categorized biological, molecular, and cellular functions influenced by repetitive manual loading, with over-representation of membrane, transmembrane, and pericellular activities. Weighted Gene Co-expression Network Analysis discerned enrichment in genes in pathways of inflammation and skeletogenesis. The present studies support previous findings of intervertebral disc cell mechanotransduction, and are the first to report comprehensively on the repertoire of gene targets influenced by mechanical loads associated with manual therapy interventions.
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