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  • 0018) sLTF compared to vehicle (aCSF, 2 µL, n=5). Bilateral nephrectomy largely prevented sLTF, affirming necessity of peripheral RAS activation. Sufficiency of central AngII signaling was assessed in nephrectomized rats. Whereas ICV AngII (0.5 ng/0.5 µL, 30 min) in nephrectomized rats exposed to sham AIH (n=4) failed to cause SNA ramping, it rescued sLTF in nephrectomized rats exposed to 5 cycles of AIH (SSNA, P=0.0227; RSNA, P=0.0390, n=5). Findings indicate that AIH causes progressive peripheral RAS activation, which stimulates an apparent threshold level of central AT1R signaling that plays a permissive role in triggering sLTF.Ankle proprioceptive deficits can contribute to increased fall risks in the elderly population. We investigated if ankle proprioception alters with age in healthy people, n = 80, aged 19 - 80 years. https://www.selleckchem.com/products/sn-38.html Previous studies report conflicting results, but none have considered that proprioceptive performance is affected by previous muscle contractions and length changes. Participants sat with their leg extended and foot rested on a motorised foot plate. Three proprioceptive tests were performed; threshold for detection of passive movement, proprioceptive reaction time, and a test of matching joint position sense. Muscle spindle sensitivity was controlled by repetitively moving the ankle, in a set pattern, before each target angle. Reliability of these methods was tested. Linear regression of proprioceptive measures against age showed proprioceptive function was unaltered. Mean detection threshold 0.13 ± 0.10⁰ (mean±SD; R2 = 0.009, p = 0.399). Reaction time 0.251 ± 0.054 s (R2 = 0.004, p = 0.597). Joint position sense responses were regressed against target angles for each participant; mean y-intercept -13.3±9.4⁰ (R2 = 0.02, p = 0.19), slope 1.15±0.45 (R2 = 0.01, p = 0.36) and R2 0.78±0.12 (R2 = 0.019, p = 0.23). Most measures showed good to excellent reliability. Unexpectedly, our results suggest there is little effect of age on ankle proprioceptive performance in healthy community-dwelling people when proprioception is tested with passive movements and under controlled laboratory conditions. However, we cannot rule out that impairments in proprioceptive function may be evident in older people with poor function i.e. those classified as 'fallers'.Disorders of the fractality of an airway tree and a vessel tree have been studied in pulmonary diseases. Here, we successfully applied Mishima's D to the bronchial minimal inner cross-sectional area (iCSA) measured in multi-detector computed tomography (****) images of chronic obstructive pulmonary disease (COPD) and non-COPD smokers (n = 162), by defining D in the following formula; logN(≥X) = - D * logX + c, where X is a certain iCSA value, and N(≥X) is the number of airway branches having iCSA greater than or equal to X. Mathematically, this D of iCSA was associated with the expected reduction ratio of iCSA at bifurcations, which can be estimated by 2-1/D. This D of iCSA also correlated weakly with the box-counting fractal dimension and Weibel's reduction ratio over airway generations, which indicated that the airway tree was not a perfect fractal object and that the branch bifurcation was asymmetrical. The D of iCSA showed positive correlations with lung function measurements of airflow limitation in study participants. In addition, D of iCSA representing the periphery showed an association with future body mass index reduction, most likely as an indicator of energy efficacy for breathing as predicted by Hess-Murray's law. D of iCSA may be helpful to understand the pathogenesis of obstructive lung diseases.Women are at higher risk for developing heart failure with preserved ejection fraction (HFpEF). We examined the utility of peak exercise blood pressure (BP) in identifying pre-clinical features of HFpEF, namely vascular and cardiac stiffness in middle-aged women. We studied 47 healthy, non-obese middle-aged women (53 ± 5 yrs). Oxygen uptake (V̇O2) and BP were assessed at rest and maximal treadmill exercise. Resting cardiac function and stiffness were assessed by echocardiography and invasive measurement (right heart catheterization) of left ventricular (LV) filling pressure under varying preloads. LV stiffness was calculated by curve fit of the diastolic portion of the pressure-volume curve. Aortic pulse wave velocity (PWV) was measured by arterial tonometry. Body fat was measured using dual-energy X-ray absorptiometry. Subjects in the highest exercise BP tertile had peak systolic BP of 201 ± 11 mmHg compared to 142 ± 19 mmHg in the lowest tertile (p less then 0.001). Higher exercise BP was associated with increased age, percent body fat, smaller LV size, slower LV relaxation, increased LV and vascular stiffness. After adjustment, LV and arterial stiffness remained significantly associated with peak exercise BP. There was a trend towards increased body fat and slowed LV relaxation (both p less then 0.07). In otherwise healthy middle-aged women, elevated exercise BP was independently associated with increased vascular stiffness and a smaller, stiffer LV - functional and structural risk factors characteristic for stage A and B HFpEF.High-intensity exercise inhibits appetite in part via alterations in the peripheral concentrations of the appetite-regulating hormones acylated ghrelin, active glucagon-like peptide-1 (GLP-1), and active peptide tyrosine-tyrosine (PYY). Given lactate may mediate these effects, we utilized sodium bicarbonate (NaHCO3) supplementation in a double-blind, placebo controlled, crossover design to investigate lactate's purported role in exercise-induced appetite suppression. Eleven males completed two identical high-intensity interval training sessions (10 x 1 min cycling bouts at ~90% heart rate maximum interspersed with 1 min recovery), where they ingested either NaHCO3 (BICARB) or sodium chloride (NaCl) as a placebo (PLACEBO) pre-exercise. Blood lactate, acylated ghrelin, GLP-1, and PYY concentrations, as well as overall appetite were assessed pre-exercise and 0, 30, 60, and 90 min post-exercise. Blood lactate was greater immediately (P less then 0.001) and 30 min post-exercise (P=0.049) in the BICARB session with an increased (P=0.
    0018) sLTF compared to vehicle (aCSF, 2 µL, n=5). Bilateral nephrectomy largely prevented sLTF, affirming necessity of peripheral RAS activation. Sufficiency of central AngII signaling was assessed in nephrectomized rats. Whereas ICV AngII (0.5 ng/0.5 µL, 30 min) in nephrectomized rats exposed to sham AIH (n=4) failed to cause SNA ramping, it rescued sLTF in nephrectomized rats exposed to 5 cycles of AIH (SSNA, P=0.0227; RSNA, P=0.0390, n=5). Findings indicate that AIH causes progressive peripheral RAS activation, which stimulates an apparent threshold level of central AT1R signaling that plays a permissive role in triggering sLTF.Ankle proprioceptive deficits can contribute to increased fall risks in the elderly population. We investigated if ankle proprioception alters with age in healthy people, n = 80, aged 19 - 80 years. https://www.selleckchem.com/products/sn-38.html Previous studies report conflicting results, but none have considered that proprioceptive performance is affected by previous muscle contractions and length changes. Participants sat with their leg extended and foot rested on a motorised foot plate. Three proprioceptive tests were performed; threshold for detection of passive movement, proprioceptive reaction time, and a test of matching joint position sense. Muscle spindle sensitivity was controlled by repetitively moving the ankle, in a set pattern, before each target angle. Reliability of these methods was tested. Linear regression of proprioceptive measures against age showed proprioceptive function was unaltered. Mean detection threshold 0.13 ± 0.10⁰ (mean±SD; R2 = 0.009, p = 0.399). Reaction time 0.251 ± 0.054 s (R2 = 0.004, p = 0.597). Joint position sense responses were regressed against target angles for each participant; mean y-intercept -13.3±9.4⁰ (R2 = 0.02, p = 0.19), slope 1.15±0.45 (R2 = 0.01, p = 0.36) and R2 0.78±0.12 (R2 = 0.019, p = 0.23). Most measures showed good to excellent reliability. Unexpectedly, our results suggest there is little effect of age on ankle proprioceptive performance in healthy community-dwelling people when proprioception is tested with passive movements and under controlled laboratory conditions. However, we cannot rule out that impairments in proprioceptive function may be evident in older people with poor function i.e. those classified as 'fallers'.Disorders of the fractality of an airway tree and a vessel tree have been studied in pulmonary diseases. Here, we successfully applied Mishima's D to the bronchial minimal inner cross-sectional area (iCSA) measured in multi-detector computed tomography (MDCT) images of chronic obstructive pulmonary disease (COPD) and non-COPD smokers (n = 162), by defining D in the following formula; logN(≥X) = - D * logX + c, where X is a certain iCSA value, and N(≥X) is the number of airway branches having iCSA greater than or equal to X. Mathematically, this D of iCSA was associated with the expected reduction ratio of iCSA at bifurcations, which can be estimated by 2-1/D. This D of iCSA also correlated weakly with the box-counting fractal dimension and Weibel's reduction ratio over airway generations, which indicated that the airway tree was not a perfect fractal object and that the branch bifurcation was asymmetrical. The D of iCSA showed positive correlations with lung function measurements of airflow limitation in study participants. In addition, D of iCSA representing the periphery showed an association with future body mass index reduction, most likely as an indicator of energy efficacy for breathing as predicted by Hess-Murray's law. D of iCSA may be helpful to understand the pathogenesis of obstructive lung diseases.Women are at higher risk for developing heart failure with preserved ejection fraction (HFpEF). We examined the utility of peak exercise blood pressure (BP) in identifying pre-clinical features of HFpEF, namely vascular and cardiac stiffness in middle-aged women. We studied 47 healthy, non-obese middle-aged women (53 ± 5 yrs). Oxygen uptake (V̇O2) and BP were assessed at rest and maximal treadmill exercise. Resting cardiac function and stiffness were assessed by echocardiography and invasive measurement (right heart catheterization) of left ventricular (LV) filling pressure under varying preloads. LV stiffness was calculated by curve fit of the diastolic portion of the pressure-volume curve. Aortic pulse wave velocity (PWV) was measured by arterial tonometry. Body fat was measured using dual-energy X-ray absorptiometry. Subjects in the highest exercise BP tertile had peak systolic BP of 201 ± 11 mmHg compared to 142 ± 19 mmHg in the lowest tertile (p less then 0.001). Higher exercise BP was associated with increased age, percent body fat, smaller LV size, slower LV relaxation, increased LV and vascular stiffness. After adjustment, LV and arterial stiffness remained significantly associated with peak exercise BP. There was a trend towards increased body fat and slowed LV relaxation (both p less then 0.07). In otherwise healthy middle-aged women, elevated exercise BP was independently associated with increased vascular stiffness and a smaller, stiffer LV - functional and structural risk factors characteristic for stage A and B HFpEF.High-intensity exercise inhibits appetite in part via alterations in the peripheral concentrations of the appetite-regulating hormones acylated ghrelin, active glucagon-like peptide-1 (GLP-1), and active peptide tyrosine-tyrosine (PYY). Given lactate may mediate these effects, we utilized sodium bicarbonate (NaHCO3) supplementation in a double-blind, placebo controlled, crossover design to investigate lactate's purported role in exercise-induced appetite suppression. Eleven males completed two identical high-intensity interval training sessions (10 x 1 min cycling bouts at ~90% heart rate maximum interspersed with 1 min recovery), where they ingested either NaHCO3 (BICARB) or sodium chloride (NaCl) as a placebo (PLACEBO) pre-exercise. Blood lactate, acylated ghrelin, GLP-1, and PYY concentrations, as well as overall appetite were assessed pre-exercise and 0, 30, 60, and 90 min post-exercise. Blood lactate was greater immediately (P less then 0.001) and 30 min post-exercise (P=0.049) in the BICARB session with an increased (P=0.
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  • We therefore speculate that an increased anaplerotic metabolism fuels the Krebs-cycle and a corresponding higher accessibility to energy fastens the recurrence in PDAC patients. Therein, a therapeutic intervention could delay PDAC recurrence and prolong survival of affected patients or could serve as biomarker to predict recurrence in the future.Orthogonal Chirp Division Multiplexing (OCDM) is a modulation scheme which outperforms the conventional Orthogonal Frequency Division Multiplexing (OFDM) under frequency selective channels by using chirp subcarriers. However, low complexity equalization algorithms for OCDM based systems under doubly selective channels have not been investigated yet. Moreover, in OCDM, the usage of different phase matrices in modulation will lead to extra storage overhead. In this paper, we investigate an OCDM based modulation scheme termed uniform phase-Orthogonal Chirp Division Multiplexing (UP-OCDM) for high-speed communication over doubly selective channels. With uniform phase matrices equipped, UP-OCDM can reduce the storage requirement of modulation. We also prove that like OCDM, the transform matrix of UP-OCDM is circulant. Based on the circulant transform matrix, we show that the channel matrices in UP-OCDM system over doubly selective channels have special structures that (1) the equivalent frequency-domain channel matrix can be approximated as a band matrix, and (2) the transform domain channel matrix in the framework of the basis expansion model (BEM) is a sum of the product of diagonal and circulant matrices. Based on these special channel structures, two low-complexity equalization algorithms are proposed for UP-OCDM in this paper. The equalization algorithms are based on block LDL H factorization and iterative matrix inversion, respectively. Numerical simulations are finally proposed to show the performance of UP-OCDM and the validity of the proposed low complexity equalization algorithms. It is shown that when the channel is doubly selective, UP-OCDM and OCDM have similar BER performance, and both of them outperform OFDM. Moreover, the proposed low complexity equalizers for UP-OCDM both show better BER performance than their OFDM counterparts.At the point of purchase, consumers often use extrinsic cues such as color, marbling, leanness, packaging, and price to determine which meat product(s) to buy [...].Conduits for the repair of peripheral nerve gaps are a good alternative to autografts as they provide a protected environment and a physical guide for axonal re-growth. Conduits require colonization by cells involved in nerve regeneration (Schwann cells, fibroblasts, endothelial cells, macrophages) while in the autograft many cells are resident and just need to be activated. Since it is known that soluble Neuregulin1 (sNRG1) is released after injury and plays an important role activating Schwann cell dedifferentiation, its expression level was investigated in early regeneration steps (7, 14, 28 days) inside a 10 mm chitosan conduit used to repair median nerve gaps in Wistar rats. In vivo data show that sNRG1, mainly the isoform α, is highly expressed in the conduit, together with a fibroblast marker, while Schwann cell markers, including NRG1 receptors, were not. Primary culture analysis shows that nerve fibroblasts, unlike Schwann cells, express high NRG1α levels, while both express NRG1β. These data suggest that sNRG1 might be mainly expressed by fibroblasts colonizing nerve conduit before Schwann cells. Immunohistochemistry analysis confirmed NRG1 and fibroblast marker co-localization. These results suggest that fibroblasts, releasing sNRG1, might promote Schwann cell dedifferentiation to a "repair" phenotype, contributing to peripheral nerve regeneration.In the present work, the Tb3+/Eu3+ co-activated sol-gel glass-ceramic materials (GCs) containing MF3 (M = Y, La) nanocrystals were fabricated during controlled heat-treatment of silicate xerogels at 350 °C. The studies of Tb3+ → Eu3+ energy transfer process (ET) were performed by excitation and emission spectra along with luminescence decay analysis. The co-activated xerogels and GCs exhibit multicolor emission originated from 4fn-4fn optical transitions of Tb3+ (5D4 → 7FJ, J = 6-3) as well as Eu3+ ions (5D0 → 7FJ, J = 0-4). Based on recorded decay curves, it was found that there is a significant prolongation in luminescence lifetimes of the 5D4 (Tb3+) and the 5D0 (Eu3+) levels after the controlled heat-treatment of xerogels. Moreover, for both types of prepared GCs, an increase in ET efficiency was also observed (from ηET ≈ 16% for xerogels up to ηET = 37.3% for SiO2-YF3 GCs and ηET = 60.8% for SiO2-LaF3 GCs). The changes in photoluminescence behavior of rare-earth (RE3+) dopants clearly evidenced their partial segregation inside low-phonon energy fluoride environment. https://www.selleckchem.com/products/resatorvid.html The obtained results suggest that prepared SiO2-MF3Tb3+, Eu3+ GC materials could be considered for use as optical elements in RGB-lighting optoelectronic devices operating under near-ultraviolet (NUV) excitation.In our research, a reliable fluorescence sensor for the detection of sulfamethoxazole (SMZ) was developed. This method relies on graphene quantum dots (GQDs) entrapped in a silica molecularly imprinted polymer (GQDs@SMIP), which was synthesized by the polymerization using GQDs, SMZ, tetraethoxysilane (TEOS) and 3-aminopropyltriethoxysilane (APTES) as fluorescence material, template, cross-linker, and functional monomers, respectively. The GQDs@SMIP was characterized by fluorometry, Fourier-transform infrared spectroscopy, transmission and scanning electron microscopies, X-ray photoelectron spectroscopy, and powder X-ray diffraction. The GQDs@SMIP exhibited a good capacity to absorb SMZ from solution, which resulted in the quenching of the GQD fluorescence intensity. The intensity of GQDs@SMIP decreased linearly with the SMZ concentration in the range of 1 to 100 µM with a correlation coefficient of 0.99537. In addition, the fluorescence responses of GQDs@SMIP to interfering substances were investigated. The results indicated that there was no effect of interfering substances on SMZ detection. Thus, the highly selective GQDs@SMIP fluorescence sensor is an effective and promising device for SMZ detection and analysis.
    We therefore speculate that an increased anaplerotic metabolism fuels the Krebs-cycle and a corresponding higher accessibility to energy fastens the recurrence in PDAC patients. Therein, a therapeutic intervention could delay PDAC recurrence and prolong survival of affected patients or could serve as biomarker to predict recurrence in the future.Orthogonal Chirp Division Multiplexing (OCDM) is a modulation scheme which outperforms the conventional Orthogonal Frequency Division Multiplexing (OFDM) under frequency selective channels by using chirp subcarriers. However, low complexity equalization algorithms for OCDM based systems under doubly selective channels have not been investigated yet. Moreover, in OCDM, the usage of different phase matrices in modulation will lead to extra storage overhead. In this paper, we investigate an OCDM based modulation scheme termed uniform phase-Orthogonal Chirp Division Multiplexing (UP-OCDM) for high-speed communication over doubly selective channels. With uniform phase matrices equipped, UP-OCDM can reduce the storage requirement of modulation. We also prove that like OCDM, the transform matrix of UP-OCDM is circulant. Based on the circulant transform matrix, we show that the channel matrices in UP-OCDM system over doubly selective channels have special structures that (1) the equivalent frequency-domain channel matrix can be approximated as a band matrix, and (2) the transform domain channel matrix in the framework of the basis expansion model (BEM) is a sum of the product of diagonal and circulant matrices. Based on these special channel structures, two low-complexity equalization algorithms are proposed for UP-OCDM in this paper. The equalization algorithms are based on block LDL H factorization and iterative matrix inversion, respectively. Numerical simulations are finally proposed to show the performance of UP-OCDM and the validity of the proposed low complexity equalization algorithms. It is shown that when the channel is doubly selective, UP-OCDM and OCDM have similar BER performance, and both of them outperform OFDM. Moreover, the proposed low complexity equalizers for UP-OCDM both show better BER performance than their OFDM counterparts.At the point of purchase, consumers often use extrinsic cues such as color, marbling, leanness, packaging, and price to determine which meat product(s) to buy [...].Conduits for the repair of peripheral nerve gaps are a good alternative to autografts as they provide a protected environment and a physical guide for axonal re-growth. Conduits require colonization by cells involved in nerve regeneration (Schwann cells, fibroblasts, endothelial cells, macrophages) while in the autograft many cells are resident and just need to be activated. Since it is known that soluble Neuregulin1 (sNRG1) is released after injury and plays an important role activating Schwann cell dedifferentiation, its expression level was investigated in early regeneration steps (7, 14, 28 days) inside a 10 mm chitosan conduit used to repair median nerve gaps in Wistar rats. In vivo data show that sNRG1, mainly the isoform α, is highly expressed in the conduit, together with a fibroblast marker, while Schwann cell markers, including NRG1 receptors, were not. Primary culture analysis shows that nerve fibroblasts, unlike Schwann cells, express high NRG1α levels, while both express NRG1β. These data suggest that sNRG1 might be mainly expressed by fibroblasts colonizing nerve conduit before Schwann cells. Immunohistochemistry analysis confirmed NRG1 and fibroblast marker co-localization. These results suggest that fibroblasts, releasing sNRG1, might promote Schwann cell dedifferentiation to a "repair" phenotype, contributing to peripheral nerve regeneration.In the present work, the Tb3+/Eu3+ co-activated sol-gel glass-ceramic materials (GCs) containing MF3 (M = Y, La) nanocrystals were fabricated during controlled heat-treatment of silicate xerogels at 350 °C. The studies of Tb3+ → Eu3+ energy transfer process (ET) were performed by excitation and emission spectra along with luminescence decay analysis. The co-activated xerogels and GCs exhibit multicolor emission originated from 4fn-4fn optical transitions of Tb3+ (5D4 → 7FJ, J = 6-3) as well as Eu3+ ions (5D0 → 7FJ, J = 0-4). Based on recorded decay curves, it was found that there is a significant prolongation in luminescence lifetimes of the 5D4 (Tb3+) and the 5D0 (Eu3+) levels after the controlled heat-treatment of xerogels. Moreover, for both types of prepared GCs, an increase in ET efficiency was also observed (from ηET ≈ 16% for xerogels up to ηET = 37.3% for SiO2-YF3 GCs and ηET = 60.8% for SiO2-LaF3 GCs). The changes in photoluminescence behavior of rare-earth (RE3+) dopants clearly evidenced their partial segregation inside low-phonon energy fluoride environment. https://www.selleckchem.com/products/resatorvid.html The obtained results suggest that prepared SiO2-MF3Tb3+, Eu3+ GC materials could be considered for use as optical elements in RGB-lighting optoelectronic devices operating under near-ultraviolet (NUV) excitation.In our research, a reliable fluorescence sensor for the detection of sulfamethoxazole (SMZ) was developed. This method relies on graphene quantum dots (GQDs) entrapped in a silica molecularly imprinted polymer (GQDs@SMIP), which was synthesized by the polymerization using GQDs, SMZ, tetraethoxysilane (TEOS) and 3-aminopropyltriethoxysilane (APTES) as fluorescence material, template, cross-linker, and functional monomers, respectively. The GQDs@SMIP was characterized by fluorometry, Fourier-transform infrared spectroscopy, transmission and scanning electron microscopies, X-ray photoelectron spectroscopy, and powder X-ray diffraction. The GQDs@SMIP exhibited a good capacity to absorb SMZ from solution, which resulted in the quenching of the GQD fluorescence intensity. The intensity of GQDs@SMIP decreased linearly with the SMZ concentration in the range of 1 to 100 µM with a correlation coefficient of 0.99537. In addition, the fluorescence responses of GQDs@SMIP to interfering substances were investigated. The results indicated that there was no effect of interfering substances on SMZ detection. Thus, the highly selective GQDs@SMIP fluorescence sensor is an effective and promising device for SMZ detection and analysis.
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  • Background Despite an initial steep decrease in alcohol misuse among Estonians through structural intervention means and the scaling up of alcohol counselling in the mid-2000's, most of the country's alcohol misuse indicators remain clearly higher than European averages. Consequently, an online self-help program was launched as part of an initial behavioral intervention initiative to foster progress in alcohol prevention on a population level. Methods A two-arm randomized controlled trial (RCT) has been designed to compare the efficacy of a culturally-adapted minimal-guidance online self-help program, the 8-week "Selge" online program against a control condition that consists of a self-administered test of alcohol use and advice regarding usual treatment in Estonia. A target sample of 600 individuals will be recruited and randomly assigned to either condition. The program will contain 10 modules based on principles of cognitive behavioural therapy (CBT) and motivational interviewing (MI). Participants in the d 04/06/2019 retrospectively.Background There is an ever-growing number of patients requiring aortic valve replacement (AVR). Limited data is available on the long-term outcomes and structural integrity of bioprosthetic valves in younger patients undergoing surgical AVR. Methods The INSPIRIS RESILIA Durability Registry (INDURE) is a prospective, open-label, multicentre, international registry with a follow-up of 5 years to assess clinical outcomes of patients younger than 60 years who undergo surgical AVR using the INSPIRIS RESILIA aortic valve. INDURE will be conducted across 20-22 sites in Europe and Canada and intends to enrol minimum of 400 patients. Patients will be included if they are scheduled to undergo AVR with or without concomitant root replacement and/or coronary bypass surgery. The primary objectives are to 1) determine VARC-2 defined time-related valve safety at one-year (depicted as freedom from events) and 2) determine freedom from stage 3 structural valve degeneration (SVD) presenting as morphological abnormalities and severe haemodynamic valve degeneration at 5 years. Secondary objectives include the assessment of the haemodynamic performance of the valve, all stages of SVD, potential valve-in-valve procedures, clinical outcomes (in terms of New York Heart Association [NYHA] function class and freedom from valve-related rehospitalisation) and change in patient quality-of-life. Discussion INDURE is a prospective, multicentre registry in Europe and Canada, which will provide **** needed data on the long-term performance of bioprosthetic valves in general and the INSPIRIS RESILIA valve in particular. The data may help to gather a deeper understanding of the longevity of bioprosthetic valves and may expand the use of bioprosthetic valves in patients under the age of 60 years. Trial registration ClinicalTrials.gov identifier NCT03666741 (registration received September, 12th, 2018).Background Clinical Practice Guidelines (CPGs) synthesize the best available evidence to guide clinician and patient decision making. There are a multitude of barriers and facilitators to clinicians adhering to CPGs; however, little is known about active cancer treatment CPG adherence specifically. This systematic review sought to identify clinician attitudes, and perceived barriers and facilitators to active cancer treatment CPG adherence. Methods A systematic search was undertaken of five databases; Ovid Medline, PsychInfo, Embase, Scopus, CINAHL, and PROQUEST. The retrieved abstracts were screened for eligibility against inclusion criteria, and a full text review was conducted of all eligible studies. Data were extracted, and a quality assessment was conducted of all included studies. The qualitative papers were thematically analyzed. Attitudes, barriers, and facilitating factors extracted from the quantitative papers were categorized within the qualitative thematic framework. Results The search resulted iians is influenced by multiple factors such as attitudes, practices, and access to resources. The review has also revealed many similarities and differences in the factors associated with general CPG, and active cancer treatment CPG, adherence. These findings will inform tailored implementation strategies to increase adherence to cancer treatment CPGs. Trial registration PROSPERO (2019) CRD42019125748.Background To investigate the loco-regional progression-free survival (LPFS) of intensity-modulated radiotherapy (IMRT) with different fraction sizes for locally advanced non-small-cell lung cancer (LANSCLC), and to apply a new radiobiological model for tumor control probability (TCP). Methods One hundred and three LANSCLC patients treated with concurrent radiochemotherapy were retrospectively analyzed. Factors potentially predictive of LPFS were assessed in the univariate and multivariate analysis. Patients were divided into group A (2.0 ≤ fraction size less then 2.2Gy), B (2.2 ≤ fraction size less then 2.5Gy), and C (2.5 ≤ fraction size≤3.1Gy) according to the tertiles of fraction size. A novel LQRG/TCP model, incorporating four "R"s of radiobiology and Gompertzian tumor growth, was developed to predict LPFS and compared with the classical LQ/TCP model. Results With a median follow-up of 22.1 months, the median LPFS was 23.8 months. Fraction size was independently prognostic of LPFS. The median LPFS of group A, B and C was 13.8, 35.7 months and not reached, respectively. Using the new LQRG/TCP model, the average absolute and relative fitting errors for LPFS were 6.9 and 19.6% for group A, 5.5 and 8.8% for group B, 6.6 and 9.5% for group C, compared with 9.5 and 29.4% for group A, 16.6 and 36.7% for group B, 24.8 and 39.1% for group C using the conventional LQ/TCP model. Conclusions Hypo-fractionated IMRT could be an effective approach for dose intensification in LANSCLC. Compared with conventional LQ model, the LQRG model showed a better performance in predicting follow-up time dependent LPFS.Background Prostate MRI has become a corner stone in diagnosis of prostate cancer (PC). Diffusion weighted imaging and the apparent diffusion coefficient (ADC) can be used to reflect tumor microstructure. The present analysis sought to compare ADC values of clinically insignificant with clinical significant PC based upon a large patient sample. https://www.selleckchem.com/ Methods MEDLINE library and SCOPUS databases were screened for the associations between ADC and Gleason score (GS) in PC up to May 2019. The primary endpoint of the systematic review was the ADC value of PC groups according to Gleason score. In total 26 studies were suitable for the analysis and included into the present study. The included studies comprised a total of 1633 lesions. Results Clinically significant PCs (GS ≥ 7) were diagnosed in 1078 cases (66.0%) and insignificant PCs (GS 5 and 6) in 555 cases (34.0%). The pooled mean ADC value derived from monoexponenantially fitted ADCmean of the clinically significant PC was 0.86 × 10- 3 mm2/s [95% CI 0.83-0.90] and the pooled mean value of insignificant PC was 1.
    Background Despite an initial steep decrease in alcohol misuse among Estonians through structural intervention means and the scaling up of alcohol counselling in the mid-2000's, most of the country's alcohol misuse indicators remain clearly higher than European averages. Consequently, an online self-help program was launched as part of an initial behavioral intervention initiative to foster progress in alcohol prevention on a population level. Methods A two-arm randomized controlled trial (RCT) has been designed to compare the efficacy of a culturally-adapted minimal-guidance online self-help program, the 8-week "Selge" online program against a control condition that consists of a self-administered test of alcohol use and advice regarding usual treatment in Estonia. A target sample of 600 individuals will be recruited and randomly assigned to either condition. The program will contain 10 modules based on principles of cognitive behavioural therapy (CBT) and motivational interviewing (MI). Participants in the d 04/06/2019 retrospectively.Background There is an ever-growing number of patients requiring aortic valve replacement (AVR). Limited data is available on the long-term outcomes and structural integrity of bioprosthetic valves in younger patients undergoing surgical AVR. Methods The INSPIRIS RESILIA Durability Registry (INDURE) is a prospective, open-label, multicentre, international registry with a follow-up of 5 years to assess clinical outcomes of patients younger than 60 years who undergo surgical AVR using the INSPIRIS RESILIA aortic valve. INDURE will be conducted across 20-22 sites in Europe and Canada and intends to enrol minimum of 400 patients. Patients will be included if they are scheduled to undergo AVR with or without concomitant root replacement and/or coronary bypass surgery. The primary objectives are to 1) determine VARC-2 defined time-related valve safety at one-year (depicted as freedom from events) and 2) determine freedom from stage 3 structural valve degeneration (SVD) presenting as morphological abnormalities and severe haemodynamic valve degeneration at 5 years. Secondary objectives include the assessment of the haemodynamic performance of the valve, all stages of SVD, potential valve-in-valve procedures, clinical outcomes (in terms of New York Heart Association [NYHA] function class and freedom from valve-related rehospitalisation) and change in patient quality-of-life. Discussion INDURE is a prospective, multicentre registry in Europe and Canada, which will provide much needed data on the long-term performance of bioprosthetic valves in general and the INSPIRIS RESILIA valve in particular. The data may help to gather a deeper understanding of the longevity of bioprosthetic valves and may expand the use of bioprosthetic valves in patients under the age of 60 years. Trial registration ClinicalTrials.gov identifier NCT03666741 (registration received September, 12th, 2018).Background Clinical Practice Guidelines (CPGs) synthesize the best available evidence to guide clinician and patient decision making. There are a multitude of barriers and facilitators to clinicians adhering to CPGs; however, little is known about active cancer treatment CPG adherence specifically. This systematic review sought to identify clinician attitudes, and perceived barriers and facilitators to active cancer treatment CPG adherence. Methods A systematic search was undertaken of five databases; Ovid Medline, PsychInfo, Embase, Scopus, CINAHL, and PROQUEST. The retrieved abstracts were screened for eligibility against inclusion criteria, and a full text review was conducted of all eligible studies. Data were extracted, and a quality assessment was conducted of all included studies. The qualitative papers were thematically analyzed. Attitudes, barriers, and facilitating factors extracted from the quantitative papers were categorized within the qualitative thematic framework. Results The search resulted iians is influenced by multiple factors such as attitudes, practices, and access to resources. The review has also revealed many similarities and differences in the factors associated with general CPG, and active cancer treatment CPG, adherence. These findings will inform tailored implementation strategies to increase adherence to cancer treatment CPGs. Trial registration PROSPERO (2019) CRD42019125748.Background To investigate the loco-regional progression-free survival (LPFS) of intensity-modulated radiotherapy (IMRT) with different fraction sizes for locally advanced non-small-cell lung cancer (LANSCLC), and to apply a new radiobiological model for tumor control probability (TCP). Methods One hundred and three LANSCLC patients treated with concurrent radiochemotherapy were retrospectively analyzed. Factors potentially predictive of LPFS were assessed in the univariate and multivariate analysis. Patients were divided into group A (2.0 ≤ fraction size less then 2.2Gy), B (2.2 ≤ fraction size less then 2.5Gy), and C (2.5 ≤ fraction size≤3.1Gy) according to the tertiles of fraction size. A novel LQRG/TCP model, incorporating four "R"s of radiobiology and Gompertzian tumor growth, was developed to predict LPFS and compared with the classical LQ/TCP model. Results With a median follow-up of 22.1 months, the median LPFS was 23.8 months. Fraction size was independently prognostic of LPFS. The median LPFS of group A, B and C was 13.8, 35.7 months and not reached, respectively. Using the new LQRG/TCP model, the average absolute and relative fitting errors for LPFS were 6.9 and 19.6% for group A, 5.5 and 8.8% for group B, 6.6 and 9.5% for group C, compared with 9.5 and 29.4% for group A, 16.6 and 36.7% for group B, 24.8 and 39.1% for group C using the conventional LQ/TCP model. Conclusions Hypo-fractionated IMRT could be an effective approach for dose intensification in LANSCLC. Compared with conventional LQ model, the LQRG model showed a better performance in predicting follow-up time dependent LPFS.Background Prostate MRI has become a corner stone in diagnosis of prostate cancer (PC). Diffusion weighted imaging and the apparent diffusion coefficient (ADC) can be used to reflect tumor microstructure. The present analysis sought to compare ADC values of clinically insignificant with clinical significant PC based upon a large patient sample. https://www.selleckchem.com/ Methods MEDLINE library and SCOPUS databases were screened for the associations between ADC and Gleason score (GS) in PC up to May 2019. The primary endpoint of the systematic review was the ADC value of PC groups according to Gleason score. In total 26 studies were suitable for the analysis and included into the present study. The included studies comprised a total of 1633 lesions. Results Clinically significant PCs (GS ≥ 7) were diagnosed in 1078 cases (66.0%) and insignificant PCs (GS 5 and 6) in 555 cases (34.0%). The pooled mean ADC value derived from monoexponenantially fitted ADCmean of the clinically significant PC was 0.86 × 10- 3 mm2/s [95% CI 0.83-0.90] and the pooled mean value of insignificant PC was 1.
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  • Moreover, FOXO1 inhibition in temperature-optimized **** cells enhanced HuNoV replication, highlighting FOXO1 inhibition as an approach for successful virus replication. In the temperature-optimized cells, various HuNoV genotypes were successfully replicated, with GI.8 showing the highest replication levels followed by GII.1, GII.3, and GII.4. Furthermore, ultrastructural analysis of the infected cells revealed functional HuNoV replication at low temperature, with increased cellular apoptosis and decreased autophagic vacuoles. In conclusion, temperature-optimized **** cells can be used as a convenient culture model for HuNoV replication by inhibiting FOXO1, providing adaptability to different genotypes.Colorectal cancer (CRC) is regarded as one of the most common and deadly forms of cancer. Gut microbiota is vital to retain and promote several functions of intestinal. Although previous researches have shown that some gut microbiota has the abilities to inhibit tumorigenesis and prevent cancer from progressing, associative mechanisms. This review not only concentrates on the antitumor effects of metabolites produced by gut microbiota, for example, SCFA, ferrichrome, urolithins, equol and conjugated linoleic acids, but also the molecules which constituted the bacterial cell wall have the antitumor effect in the host, including lipopolysaccharide, lipoteichoic acid, β-glucans and peptidoglycan. The aim of our review is to develop a possible therapeutic method, which use the products of gut microbiota metabolism or gut microbiota constituents to help treat or prevent colorectal cancer.Amylosucrase (ASase, EC 2.4.1.4) is capable of efficient glucose transfer from sucrose acting as the sole donor molecule, to various functional acceptor compounds, such as polyphenols and flavonoids. An ASase variant from Deinococcus geothermalis, in which the 226th alanine is replaced with asparagine (DgAS-A226N), shows increased polymerization activity due to changes in the flexibility of the loop near the active site. In this study, we further investigated how the mutation modulates the enzymatic activity of DgAS using molecular dynamics and docking simulations to evaluate interactions between the enzyme and phenolic compounds. The computational analysis revealed that the A226N mutation could induce and stabilize structural changes near the substrate-binding site to increase glucose transfer efficiency to phenolic compounds. Kinetic parameters of DgAS-A226N and WT DgAS were determined with sucrose and 4-methylumbelliferone (MU) as donor and acceptor molecules, respectively. The Kcat/Km value of DgAS-A226N with MU (6.352 mM-1min-1) was significantly higher than that of DgAS (5.296 mM-1min-1). The enzymatic activity was tested with a small phenolic compound, hydroquinone, and there was a 1.4-fold increase in α-arbutin production. From the results of the study, it was concluded that DgAS-A226N has improved acceptor specificity toward small phenolic compounds by way of stabilizing the active conformation of these compounds.Low-quality soil for land reuse is a crucial problem in vegetation construction proceedings of waste disposal sites in mining areas. It is necessary to find suitable materials to improve the soil quality, especially increase soil microbial diversity and activity. In this study, pot experiments were conducted to investigate the effect of a mixed material of humic acid, super absorbent polymer and biochar on low-quality soil indexes and the microbial community response. The indexes included soil physicochemical properties and the corresponding plant growth. The results showed that the mixed material could improve chemical properties and physical structure of soil by increasing the bulk density, porosity, macro aggregate, and promote the mineralization of nutrient elements in soil. The best performance was achieved by adding 3 g·kg-1 super absorbent polymer, 3 g·kg-1 humic acid, and 10 g·kg-1 biochar to soil with plant total nitrogen, dry weight and height increased by 85.18%, 266.41% and 74.06%, respectively. Physicochemical properties caused changes in soil microbial diversity. Acidobacteria, Bacteroidetes, Chloroflexi, Cyanobacteria, Firmicutes, Nitrospirae, Planctomycetes, and Proteobacteria were significantly positively correlated with most of the physical, chemical and plant indicators. Actinobacteria and Armatimonadetes were significantly negatively correlated with most measurement factors. This study contributes to developing a possible amendment for low-quality soil improving the understanding of soil microbial functions and sustainability.Previously, we performed an in silico analysis of the Periplaneta americana transcriptome. Antimicrobial peptide candidates were selected using an in silico antimicrobial peptide prediction method. It was found that periplanetasin-5 had antimicrobial activity against yeast and gram-positive and -negative bacteria. In the present study, we demonstrated the anti-inflammatory activities of periplanetasin-5 in mouse macrophage Raw264.7 cells. No cytotoxicity was observed at 60 μg/ml periplanetasin-5, and treatment decreased nitric oxide production in Raw264.7 cells exposed to lipopolysaccharide (LPS). In addition, quantitative RT-PCR and enzyme-linked immunosorbent assay revealed that periplanetasin-5 reduced cytokine (tumor necrosis factor-α, interleukin-6) expression levels in the Raw264.7 cells. Periplanetasin-5 controlled inflammation by inhibiting phosphorylation of MAPKs, an inflammatory signaling element, and reducing the degradation of IκB. Through LAL assay, LPS toxicity was found to decrease in a periplanetasin-5 dose-dependent manner. Collectively, these data showed that periplanetasin-5 had anti-inflammatory activities, exemplified in LPS-exposed Raw264.7 cells. Thus, we have provided a potentially useful antibacterial peptide candidate with anti-inflammatory activities.Lactic acid bacteria (LAB) play an important role in dairy fermentations, notably as cheese starter cultures. https://www.selleckchem.com/products/Erlotinib-Hydrochloride.html During the cheese production and ripening period, various enzymes from milk, rennet, starter cultures, and non-starter LABs are involved in flavor formation pathways, including glycolysis, proteolysis, and lipolysis. Among these three pathways, starter LABs are particularly related to amino acid degradation, presumably as the origins of major flavor compounds. Therefore, several enzymes were major criteria for the selection of starter bacteria with flavor-forming ability. Lactococcus lactis subsp. lactis LDTM6802 and Lactococcus lactis subsp. cremoris LDTM6803, isolated from Korean raw milk and cucumber kimchi, were confirmed by using multiplex PCR and characterized as starter bacteria. The combinations of starter bacteria were validated in a miniature Gouda-type cheese model. The flavor compounds of the tested miniature cheeses were analyzed and profiled by using an electronic nose. Compared to commercial industrial cheese starters, selected starter bacteria showed lower pH, and more variety in their flavor profile.
    Moreover, FOXO1 inhibition in temperature-optimized MDCK cells enhanced HuNoV replication, highlighting FOXO1 inhibition as an approach for successful virus replication. In the temperature-optimized cells, various HuNoV genotypes were successfully replicated, with GI.8 showing the highest replication levels followed by GII.1, GII.3, and GII.4. Furthermore, ultrastructural analysis of the infected cells revealed functional HuNoV replication at low temperature, with increased cellular apoptosis and decreased autophagic vacuoles. In conclusion, temperature-optimized MDCK cells can be used as a convenient culture model for HuNoV replication by inhibiting FOXO1, providing adaptability to different genotypes.Colorectal cancer (CRC) is regarded as one of the most common and deadly forms of cancer. Gut microbiota is vital to retain and promote several functions of intestinal. Although previous researches have shown that some gut microbiota has the abilities to inhibit tumorigenesis and prevent cancer from progressing, associative mechanisms. This review not only concentrates on the antitumor effects of metabolites produced by gut microbiota, for example, SCFA, ferrichrome, urolithins, equol and conjugated linoleic acids, but also the molecules which constituted the bacterial cell wall have the antitumor effect in the host, including lipopolysaccharide, lipoteichoic acid, β-glucans and peptidoglycan. The aim of our review is to develop a possible therapeutic method, which use the products of gut microbiota metabolism or gut microbiota constituents to help treat or prevent colorectal cancer.Amylosucrase (ASase, EC 2.4.1.4) is capable of efficient glucose transfer from sucrose acting as the sole donor molecule, to various functional acceptor compounds, such as polyphenols and flavonoids. An ASase variant from Deinococcus geothermalis, in which the 226th alanine is replaced with asparagine (DgAS-A226N), shows increased polymerization activity due to changes in the flexibility of the loop near the active site. In this study, we further investigated how the mutation modulates the enzymatic activity of DgAS using molecular dynamics and docking simulations to evaluate interactions between the enzyme and phenolic compounds. The computational analysis revealed that the A226N mutation could induce and stabilize structural changes near the substrate-binding site to increase glucose transfer efficiency to phenolic compounds. Kinetic parameters of DgAS-A226N and WT DgAS were determined with sucrose and 4-methylumbelliferone (MU) as donor and acceptor molecules, respectively. The Kcat/Km value of DgAS-A226N with MU (6.352 mM-1min-1) was significantly higher than that of DgAS (5.296 mM-1min-1). The enzymatic activity was tested with a small phenolic compound, hydroquinone, and there was a 1.4-fold increase in α-arbutin production. From the results of the study, it was concluded that DgAS-A226N has improved acceptor specificity toward small phenolic compounds by way of stabilizing the active conformation of these compounds.Low-quality soil for land reuse is a crucial problem in vegetation construction proceedings of waste disposal sites in mining areas. It is necessary to find suitable materials to improve the soil quality, especially increase soil microbial diversity and activity. In this study, pot experiments were conducted to investigate the effect of a mixed material of humic acid, super absorbent polymer and biochar on low-quality soil indexes and the microbial community response. The indexes included soil physicochemical properties and the corresponding plant growth. The results showed that the mixed material could improve chemical properties and physical structure of soil by increasing the bulk density, porosity, macro aggregate, and promote the mineralization of nutrient elements in soil. The best performance was achieved by adding 3 g·kg-1 super absorbent polymer, 3 g·kg-1 humic acid, and 10 g·kg-1 biochar to soil with plant total nitrogen, dry weight and height increased by 85.18%, 266.41% and 74.06%, respectively. Physicochemical properties caused changes in soil microbial diversity. Acidobacteria, Bacteroidetes, Chloroflexi, Cyanobacteria, Firmicutes, Nitrospirae, Planctomycetes, and Proteobacteria were significantly positively correlated with most of the physical, chemical and plant indicators. Actinobacteria and Armatimonadetes were significantly negatively correlated with most measurement factors. This study contributes to developing a possible amendment for low-quality soil improving the understanding of soil microbial functions and sustainability.Previously, we performed an in silico analysis of the Periplaneta americana transcriptome. Antimicrobial peptide candidates were selected using an in silico antimicrobial peptide prediction method. It was found that periplanetasin-5 had antimicrobial activity against yeast and gram-positive and -negative bacteria. In the present study, we demonstrated the anti-inflammatory activities of periplanetasin-5 in mouse macrophage Raw264.7 cells. No cytotoxicity was observed at 60 μg/ml periplanetasin-5, and treatment decreased nitric oxide production in Raw264.7 cells exposed to lipopolysaccharide (LPS). In addition, quantitative RT-PCR and enzyme-linked immunosorbent assay revealed that periplanetasin-5 reduced cytokine (tumor necrosis factor-α, interleukin-6) expression levels in the Raw264.7 cells. Periplanetasin-5 controlled inflammation by inhibiting phosphorylation of MAPKs, an inflammatory signaling element, and reducing the degradation of IκB. Through LAL assay, LPS toxicity was found to decrease in a periplanetasin-5 dose-dependent manner. Collectively, these data showed that periplanetasin-5 had anti-inflammatory activities, exemplified in LPS-exposed Raw264.7 cells. Thus, we have provided a potentially useful antibacterial peptide candidate with anti-inflammatory activities.Lactic acid bacteria (LAB) play an important role in dairy fermentations, notably as cheese starter cultures. https://www.selleckchem.com/products/Erlotinib-Hydrochloride.html During the cheese production and ripening period, various enzymes from milk, rennet, starter cultures, and non-starter LABs are involved in flavor formation pathways, including glycolysis, proteolysis, and lipolysis. Among these three pathways, starter LABs are particularly related to amino acid degradation, presumably as the origins of major flavor compounds. Therefore, several enzymes were major criteria for the selection of starter bacteria with flavor-forming ability. Lactococcus lactis subsp. lactis LDTM6802 and Lactococcus lactis subsp. cremoris LDTM6803, isolated from Korean raw milk and cucumber kimchi, were confirmed by using multiplex PCR and characterized as starter bacteria. The combinations of starter bacteria were validated in a miniature Gouda-type cheese model. The flavor compounds of the tested miniature cheeses were analyzed and profiled by using an electronic nose. Compared to commercial industrial cheese starters, selected starter bacteria showed lower pH, and more variety in their flavor profile.
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  • Skin picking disorder (excoriation disorder) is a common psychodermatological disorder characterized by irresistible urges to pick skin on dominant hand accessible parts of the body. There is no specific recommended treatment available. Various pharmacological agents particularly selective serotonin reuptake inhibitors and glutamatergic agents have been tried with variable success. Habit reversal therapy has been commonly employed in the treatment and has some evidence-based success. This review focuses on the interdisciplinary team approach consisting of a liaison with psychiatry, in the management of this disorder. The specific roles of dermatologist and psychiatrist are discussed in detail.Background and aim Endoscopic submucosal dissection (ESD) has a high en bloc resection rate and is widely performed for large colorectal lesions. However, colorectal ESD is associated with a high frequency of adverse events (AEs), and the efficacy of prophylactic endoscopic closure after ESD for preventing AEs is still controversial. This meta-analysis was conducted to assess the efficacy of closure on AEs following colorectal ESD. Methods We searched PubMed, Embase, and the Cochrane Library for eligible studies. The chi-square-based Q statistics and the I2 test were used to test for heterogeneity. Pooling was conducted using a fixed or random effects model. Results We identified eight eligible studies that compared the effects of closure vs non-closure with respect to delayed bleeding, delayed perforation, and post-ESD coagulation syndrome. Compared with non-closure (5.2%), closure was associated with a lower incidence (0.9%) of delayed bleeding (pooled odd ratios [ORs]0.19, 95% CI 0.08-0.49) following ESD. The pooled ORs showed no significant differences in incidence of delayed perforation (pooled OR 0.22; 95% CI 0.05-1.03) or post-ESD coagulation syndrome (pooled OR0.75; 95% CI 0.26-2.18) between the closure and non-closure groups. Conclusion Prophylactic endoscopic closure may reduce the incidence of delayed bleeding following ESD of colorectal lesions. Future studies are needed to further illuminate risk factors and stratify high risk subjects for a cost-effective preventive strategy.Impulse control disorders (ICDs) in Parkinson's disease (PD) are defined as a failure to resist an "urge" to behave in a way that may be debilitating for oneself or others. The suggested immobilization test (SIT) has been developed to assess the "urge" to move and support the diagnosis of restless legs syndrome (RLS) in the general population and in PD. A clinical association between RLS and ICDs has been shown in PD and in the general population. We hypothesized that there could be a semiological overlap between RLS and ICDs, and conducted SIT in PD patients with and without ICDs. Fifty PD patients with (n = 17) and without (n = 33) current ICDs were included. SIT, videopolysomnography, demographical treatment, and motor, psycho-behavioural and sleep characteristics, including RLS, were recorded. PD patients with ICDs reported increased subjective discomfort during SIT (SD-SIT) compared to those without ICDs (p = .024). Multivariable analysis confirmed ICDs as an independent factor associated with increased SD-SIT in PD, regardless of the presence of RLS, PD severity and dopamine agonist treatment dose. https://www.selleckchem.com/products/resatorvid.html The discomfort measured by SIT might not only reflect the "urge" to move in RLS but also the ICDs in PD, suggesting that ICDs and RLS in PD could share a common phenomenology.Introduction & aim Several newer medications have emerged for the management of lower urinary tract symptoms secondary to benign prostate hyperplasia (BPH). The efficacy/safety of PDE-5 inhibitors (Tadalafil 5 mg) in BPH-lower urinary tract symptoms (LUTS) has been sparingly assessed in the published English literature as compared with their established role in erectile dysfunction. We aim to assess the efficacy/safety of tadalafil vs tamsulosin in symptomatic patients of BPH in a tertiary care teaching institution. Methods After obtaining an informed written consent and institutional ethics clearance, 100 patients of BPH with an IPSS score of more than 7, without any complications of the disease were computer randomised to receive therapy with either tamsulosin 0.4 mg or tadalafil 5 mg once daily for a period of 2 months. They were evaluated for its efficacy (IPSS, Peak flow rate, IIEF-5, quality of life index [QOL] and PVR) and safety (side effect profile) with monthly visit assessments for 2 months. Data wf Tadalafil monotherapy in BPH patients with predominant storage LUTS merits further evaluation with larger trials.Aims No specific questionnaire to date has been available in Polish for evaluating health-related quality of life for urinary dysfunctions associated with multiple sclerosis (MS). The aim of this study was to translate, culturally adapt, and validate Polish versions of the Qualiveen and SF-Qualiveen for use in patients with MS. Methods Cross-cultural adaptation of the original English Qualiveen and SF-Qualiveen into Polish was performed according to international recommended and standard procedures. Adult patients with MS of the Department of Urology at the Jagiellonian University, Krakow, Poland, completed the Qualiveen, SF-Qualiveen, and International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) twice at baseline and 2 weeks later. Results One hundred eighty-nine Polish-speaking patients with MS completed the questionnaires. An intercorrelation study revealed that internal consistency was good for the total Qualiveen and SF-Qualiveen (Cronbach's α >0.8). Test-retest reliability (reproducibility) demonstrated strong stability (intraclass correlation coefficient >0.8). Content validities were optimal. Significant relationships between the Qualiveen and the ICIQ-SF, as well as the SF-Qualiveen and the ICIQ-SF, confirmed good construct/criterion validity. Conclusion The Polish Qualiveen and SF-Qualiveen are reliable, valid, and consistent measures of urinary disorder-specific quality of life in patients with MS. After years of no appropriate Polish instrument being available for healthcare professionals to evaluate patients with MS, we provide these versions and recommend their use in research and clinical practice in Poland.
    Skin picking disorder (excoriation disorder) is a common psychodermatological disorder characterized by irresistible urges to pick skin on dominant hand accessible parts of the body. There is no specific recommended treatment available. Various pharmacological agents particularly selective serotonin reuptake inhibitors and glutamatergic agents have been tried with variable success. Habit reversal therapy has been commonly employed in the treatment and has some evidence-based success. This review focuses on the interdisciplinary team approach consisting of a liaison with psychiatry, in the management of this disorder. The specific roles of dermatologist and psychiatrist are discussed in detail.Background and aim Endoscopic submucosal dissection (ESD) has a high en bloc resection rate and is widely performed for large colorectal lesions. However, colorectal ESD is associated with a high frequency of adverse events (AEs), and the efficacy of prophylactic endoscopic closure after ESD for preventing AEs is still controversial. This meta-analysis was conducted to assess the efficacy of closure on AEs following colorectal ESD. Methods We searched PubMed, Embase, and the Cochrane Library for eligible studies. The chi-square-based Q statistics and the I2 test were used to test for heterogeneity. Pooling was conducted using a fixed or random effects model. Results We identified eight eligible studies that compared the effects of closure vs non-closure with respect to delayed bleeding, delayed perforation, and post-ESD coagulation syndrome. Compared with non-closure (5.2%), closure was associated with a lower incidence (0.9%) of delayed bleeding (pooled odd ratios [ORs]0.19, 95% CI 0.08-0.49) following ESD. The pooled ORs showed no significant differences in incidence of delayed perforation (pooled OR 0.22; 95% CI 0.05-1.03) or post-ESD coagulation syndrome (pooled OR0.75; 95% CI 0.26-2.18) between the closure and non-closure groups. Conclusion Prophylactic endoscopic closure may reduce the incidence of delayed bleeding following ESD of colorectal lesions. Future studies are needed to further illuminate risk factors and stratify high risk subjects for a cost-effective preventive strategy.Impulse control disorders (ICDs) in Parkinson's disease (PD) are defined as a failure to resist an "urge" to behave in a way that may be debilitating for oneself or others. The suggested immobilization test (SIT) has been developed to assess the "urge" to move and support the diagnosis of restless legs syndrome (RLS) in the general population and in PD. A clinical association between RLS and ICDs has been shown in PD and in the general population. We hypothesized that there could be a semiological overlap between RLS and ICDs, and conducted SIT in PD patients with and without ICDs. Fifty PD patients with (n = 17) and without (n = 33) current ICDs were included. SIT, videopolysomnography, demographical treatment, and motor, psycho-behavioural and sleep characteristics, including RLS, were recorded. PD patients with ICDs reported increased subjective discomfort during SIT (SD-SIT) compared to those without ICDs (p = .024). Multivariable analysis confirmed ICDs as an independent factor associated with increased SD-SIT in PD, regardless of the presence of RLS, PD severity and dopamine agonist treatment dose. https://www.selleckchem.com/products/resatorvid.html The discomfort measured by SIT might not only reflect the "urge" to move in RLS but also the ICDs in PD, suggesting that ICDs and RLS in PD could share a common phenomenology.Introduction & aim Several newer medications have emerged for the management of lower urinary tract symptoms secondary to benign prostate hyperplasia (BPH). The efficacy/safety of PDE-5 inhibitors (Tadalafil 5 mg) in BPH-lower urinary tract symptoms (LUTS) has been sparingly assessed in the published English literature as compared with their established role in erectile dysfunction. We aim to assess the efficacy/safety of tadalafil vs tamsulosin in symptomatic patients of BPH in a tertiary care teaching institution. Methods After obtaining an informed written consent and institutional ethics clearance, 100 patients of BPH with an IPSS score of more than 7, without any complications of the disease were computer randomised to receive therapy with either tamsulosin 0.4 mg or tadalafil 5 mg once daily for a period of 2 months. They were evaluated for its efficacy (IPSS, Peak flow rate, IIEF-5, quality of life index [QOL] and PVR) and safety (side effect profile) with monthly visit assessments for 2 months. Data wf Tadalafil monotherapy in BPH patients with predominant storage LUTS merits further evaluation with larger trials.Aims No specific questionnaire to date has been available in Polish for evaluating health-related quality of life for urinary dysfunctions associated with multiple sclerosis (MS). The aim of this study was to translate, culturally adapt, and validate Polish versions of the Qualiveen and SF-Qualiveen for use in patients with MS. Methods Cross-cultural adaptation of the original English Qualiveen and SF-Qualiveen into Polish was performed according to international recommended and standard procedures. Adult patients with MS of the Department of Urology at the Jagiellonian University, Krakow, Poland, completed the Qualiveen, SF-Qualiveen, and International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) twice at baseline and 2 weeks later. Results One hundred eighty-nine Polish-speaking patients with MS completed the questionnaires. An intercorrelation study revealed that internal consistency was good for the total Qualiveen and SF-Qualiveen (Cronbach's α >0.8). Test-retest reliability (reproducibility) demonstrated strong stability (intraclass correlation coefficient >0.8). Content validities were optimal. Significant relationships between the Qualiveen and the ICIQ-SF, as well as the SF-Qualiveen and the ICIQ-SF, confirmed good construct/criterion validity. Conclusion The Polish Qualiveen and SF-Qualiveen are reliable, valid, and consistent measures of urinary disorder-specific quality of life in patients with MS. After years of no appropriate Polish instrument being available for healthcare professionals to evaluate patients with MS, we provide these versions and recommend their use in research and clinical practice in Poland.
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  • 88 (Anaeromyces) to 6.57 (Piromyces) and average molecular weights were ranged from 38.7 kDa (Orpinomyces) to 56.6 kDa (Piromyces). In Carbohydrate-Active enZYmes (CAZY) database, glycoside hydrolases (36), carbohydrate binding module (11), carbohydrate esterases (8), glycosyltransferase (5) and polysaccharide lyases (3) from anaerobic fungi were registered. During four decades, 1,031 research articles about anaerobic fungi were published and 444 and 719 articles were available in PubMed (PM) and PubMed Central (PMC) DB. © Copyright 2020 Korean Society of Animal Science and Technology.The definition of meat analog refers to the replacement of the main ingredient with other than meat. It also called a meat substitute, meat alternatives, fake or **** meat, and imitation meat. The increased importance of meat analog in the current trend is due to the health awareness among consumers in their diet and for a better future environment. The factors that lead to this shift is due to low fat and calorie foods intake, flexitarians, animal disease, natural resources depletion, and to reduce greenhouse gas emission. Currently, available marketed meat analog products are plant-based meat in which the quality (i.e., texture and taste) are similar to the conventional meat. The ingredients used are mainly soy proteins with novel ingredients added, such as mycoprotein and soy leghemoglobin. However, plant-based meat is sold primarily in Western countries. Asian countries also will become a potential market in the near future due to growing interest in this product. With the current advance technology, lab-grown meat with no livestock raising or known as cultured meat will be expected to boost the food market in the future. Also, insect-based products will be promising to be the next protein resource for human food. Nevertheless, other than acceptability, cost-effective, reliable production, and consistent quality towards those products, product safety is the top priority. Therefore, the regulatory frameworks need to be developed alongside. © Copyright 2020 Korean Society of Animal Science and Technology.The correct management of patients with coronavirus disease 2019 and acute coronary syndrome is still uncertain. We describe the percutaneous treatment of an unprotected left main coronary artery in a patient who is positive for coronavirus disease 2019 with unstable angina, dyspnea and fever. Particular attention will be dedicated to the measures adopted in the catheterization laboratory to protect the staff and to avoid further spread of the infection. (Level of Difficulty Intermediate.). © 2020 The Authors.As health systems worldwide grapple with the COVID-19 pandemic, patients on durable LVAD support represent a unique population at risk for the disease. We outline such a patient who developed COVID-19 complicated by "cytokine storm" with severe ARDS and myocardial injury; and describe the challenges that arose during management. © 2020 Published by Elsevier on behalf of the American College of Cardiology Foundation.The COVID-19 outbreak has brought our lives to a sudden and complete lockdown. While the numbers of confirmed cases and deaths continue to rise, people around the world are taking brave actions to mitigate transmission and save lives. The role sports play in this pandemic is unprecedented, fascinating, and reveals the immense impact sports has on every aspect of our lives. We must all do our part to keep each other safe until this outbreak subsides and sports and humanity are **** to being greater than ever. © 2020 Published by Elsevier on behalf of the Arthroscopy Association of North America.In this paper, a novel mercury-free electrochemical probe was constructed for the trace determination of octamethylcyclotetrasiloxane (D4) in some biological fluids by adsorptive stripping voltammetry. The platform is based on the adsorptive accumulation of Ni(II) onto a carbon paste electrode modified with citrate stabilized Fe3O4 (Cit-Fe3O4) and dimethylglyoxime (DMG). It was shown that trace levels of D4 enhance the electrochemical adsorptive stripping signal of Ni(II) on the electrode platform. It was shown that electrochemical signals are proportional to concentrations of D4. The supporting electrolyte, pH and instrumental parameters associated with the electrode response, including scan rate, accumulation potential and deposition time were optimized. The electrode platform demonstrated well resolved, reproducible peaks, with relative standard deviation (RSD) of 3.8% and detection limit (3Sb/m) of 27.0 ng/mL. The sensor exhibited good D4 detection and quantification in human blood plasma and urine samples. © The Author(s) 2020.We forecast 1,000,000 COVID-19 cases outside of China by March 30, 2020 based on a heuristic and WHO situation reports. We do not model the COVID-19 pandemic; we model only the number of cases. The proposed heuristic is based on a simple observation that the plot of the given data is well approximated by an exponential curve. The exponential curve is used for forecasting the growth of new cases. It has been tested for the last situation report of the last day. Its accuracy has been 1.29% for the last day added and predicted by the 57 previous WHO situation reports (the date 18 March 2020). Prediction, forecast, pandemic, COVID-19, coronavirus, exponential growth curve parameter, heuristic, epidemiology, extrapolation, abductive reasoning, WHO situa- tion report. © 2020 Published by Elsevier Inc.Objective To demonstrate the feasibility of algorithmic prediction using a model of baseline arm movement, genetic factors, demographic characteristics, and multimodal assessment of the structure and function of motor pathways. To identify prognostic factors and the biological substrate for reductions in arm impairment in response to repetitive task practice. Design This prospective single-group interventional study seeks to predict response to a repetitive task practice program using an intent-to-treat paradigm. https://www.selleckchem.com/Caspase.html Response is measured as a change of ≥5 points on the Upper Extremity Fugl-Meyer from baseline to final evaluation (at the end of training). Setting General community. Participants Anticipated enrollment of community-dwelling adults with chronic stroke (N = 96; onset≥6mo) and moderate to severe residual hemiparesis of the upper limb as defined by a score of 10-45 points on the Upper Extremity Fugl-Meyer. Intervention The intervention is a form of repetitive task practice using a combination of robot-assisted therapy coupled with functional arm use in real-world tasks administered over 12 weeks.
    88 (Anaeromyces) to 6.57 (Piromyces) and average molecular weights were ranged from 38.7 kDa (Orpinomyces) to 56.6 kDa (Piromyces). In Carbohydrate-Active enZYmes (CAZY) database, glycoside hydrolases (36), carbohydrate binding module (11), carbohydrate esterases (8), glycosyltransferase (5) and polysaccharide lyases (3) from anaerobic fungi were registered. During four decades, 1,031 research articles about anaerobic fungi were published and 444 and 719 articles were available in PubMed (PM) and PubMed Central (PMC) DB. © Copyright 2020 Korean Society of Animal Science and Technology.The definition of meat analog refers to the replacement of the main ingredient with other than meat. It also called a meat substitute, meat alternatives, fake or mock meat, and imitation meat. The increased importance of meat analog in the current trend is due to the health awareness among consumers in their diet and for a better future environment. The factors that lead to this shift is due to low fat and calorie foods intake, flexitarians, animal disease, natural resources depletion, and to reduce greenhouse gas emission. Currently, available marketed meat analog products are plant-based meat in which the quality (i.e., texture and taste) are similar to the conventional meat. The ingredients used are mainly soy proteins with novel ingredients added, such as mycoprotein and soy leghemoglobin. However, plant-based meat is sold primarily in Western countries. Asian countries also will become a potential market in the near future due to growing interest in this product. With the current advance technology, lab-grown meat with no livestock raising or known as cultured meat will be expected to boost the food market in the future. Also, insect-based products will be promising to be the next protein resource for human food. Nevertheless, other than acceptability, cost-effective, reliable production, and consistent quality towards those products, product safety is the top priority. Therefore, the regulatory frameworks need to be developed alongside. © Copyright 2020 Korean Society of Animal Science and Technology.The correct management of patients with coronavirus disease 2019 and acute coronary syndrome is still uncertain. We describe the percutaneous treatment of an unprotected left main coronary artery in a patient who is positive for coronavirus disease 2019 with unstable angina, dyspnea and fever. Particular attention will be dedicated to the measures adopted in the catheterization laboratory to protect the staff and to avoid further spread of the infection. (Level of Difficulty Intermediate.). © 2020 The Authors.As health systems worldwide grapple with the COVID-19 pandemic, patients on durable LVAD support represent a unique population at risk for the disease. We outline such a patient who developed COVID-19 complicated by "cytokine storm" with severe ARDS and myocardial injury; and describe the challenges that arose during management. © 2020 Published by Elsevier on behalf of the American College of Cardiology Foundation.The COVID-19 outbreak has brought our lives to a sudden and complete lockdown. While the numbers of confirmed cases and deaths continue to rise, people around the world are taking brave actions to mitigate transmission and save lives. The role sports play in this pandemic is unprecedented, fascinating, and reveals the immense impact sports has on every aspect of our lives. We must all do our part to keep each other safe until this outbreak subsides and sports and humanity are back to being greater than ever. © 2020 Published by Elsevier on behalf of the Arthroscopy Association of North America.In this paper, a novel mercury-free electrochemical probe was constructed for the trace determination of octamethylcyclotetrasiloxane (D4) in some biological fluids by adsorptive stripping voltammetry. The platform is based on the adsorptive accumulation of Ni(II) onto a carbon paste electrode modified with citrate stabilized Fe3O4 (Cit-Fe3O4) and dimethylglyoxime (DMG). It was shown that trace levels of D4 enhance the electrochemical adsorptive stripping signal of Ni(II) on the electrode platform. It was shown that electrochemical signals are proportional to concentrations of D4. The supporting electrolyte, pH and instrumental parameters associated with the electrode response, including scan rate, accumulation potential and deposition time were optimized. The electrode platform demonstrated well resolved, reproducible peaks, with relative standard deviation (RSD) of 3.8% and detection limit (3Sb/m) of 27.0 ng/mL. The sensor exhibited good D4 detection and quantification in human blood plasma and urine samples. © The Author(s) 2020.We forecast 1,000,000 COVID-19 cases outside of China by March 30, 2020 based on a heuristic and WHO situation reports. We do not model the COVID-19 pandemic; we model only the number of cases. The proposed heuristic is based on a simple observation that the plot of the given data is well approximated by an exponential curve. The exponential curve is used for forecasting the growth of new cases. It has been tested for the last situation report of the last day. Its accuracy has been 1.29% for the last day added and predicted by the 57 previous WHO situation reports (the date 18 March 2020). Prediction, forecast, pandemic, COVID-19, coronavirus, exponential growth curve parameter, heuristic, epidemiology, extrapolation, abductive reasoning, WHO situa- tion report. © 2020 Published by Elsevier Inc.Objective To demonstrate the feasibility of algorithmic prediction using a model of baseline arm movement, genetic factors, demographic characteristics, and multimodal assessment of the structure and function of motor pathways. To identify prognostic factors and the biological substrate for reductions in arm impairment in response to repetitive task practice. Design This prospective single-group interventional study seeks to predict response to a repetitive task practice program using an intent-to-treat paradigm. https://www.selleckchem.com/Caspase.html Response is measured as a change of ≥5 points on the Upper Extremity Fugl-Meyer from baseline to final evaluation (at the end of training). Setting General community. Participants Anticipated enrollment of community-dwelling adults with chronic stroke (N = 96; onset≥6mo) and moderate to severe residual hemiparesis of the upper limb as defined by a score of 10-45 points on the Upper Extremity Fugl-Meyer. Intervention The intervention is a form of repetitive task practice using a combination of robot-assisted therapy coupled with functional arm use in real-world tasks administered over 12 weeks.
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  • Infusions of epinephrine titrated to treat unstable hypotension, as well as potassium for severe hypokalemia may be required. Current scientific evidence does not support treatment or prophylactic use of these agents for COVID-19 disease. Regulatory and public health authorities recognize that CQ/HCQ may offer little clinical benefit and only add risk requiring further investigation before wider public distribution.The "4E" approach to cognition argues that cognition does not occur solely in the head, but is also embodied, embedded, enacted, or extended by way of extra-cranial processes and structures. Though very **** in vogue, 4E cognition has received relatively few critical evaluations. By reflecting on two recent collections, this article reviews the 4E paradigm with a view to assessing its strengths and weaknesses.Research consortia play a key role in our understanding of how environmental exposures influence health and wellbeing, especially in the case of catastrophic events such as the Deepwater Horizon oil spill. A common challenge that prevents the optimal use of these data is the difficulty of harmonizing data regarding the environmental exposures and health effects across the studies within and among consortia. A review of the measures used by members of the Deepwater Horizon Research Consortia highlights the challenges associated with balancing timely implementation of a study to support disaster relief with optimizing the long-term value of the data. The inclusion of common, standard measures at the study design phase and a priori discussions regarding harmonization of study-specific measures among consortia members are key to overcoming this challenge. As more resources become available to support the use of standard measures, researchers now have the tools needed to rapidly coordinate their studies without compromising research focus or timely completion of the original study goals.Ultrafast lasers are becoming increasingly widespread in science and industry alike. Fiber-based ultrafast laser sources are especially attractive because of their compactness, alignment-free setups, and potentially low cost. https://www.selleckchem.com/products/ITF2357(Givinostat).html However, confining short pulses within a fiber core leads to high intensities, which drives a host of nonlinear effects. While these phenomena and their interactions greatly complicate the design of such systems, they can also provide opportunities for engineering new capabilities. Here, we report a new fiber amplification regime distinguished by the use of a dynamically evolving gain spectrum as a degree of freedom as a pulse experiences nonlinear spectral broadening, absorption and amplification actively reshape both the pulse and the gain spectrum itself. The dynamic co-evolution of the field and excited-state populations supports pulses that can broaden spectrally by almost two orders of magnitude and well beyond the gain bandwidth, while remaining cleanly compressible to their sub-50-fs transform limit. Theory and experiments provide evidence that a nonlinear attractor underlies the management of the nonlinearity by the gain. Further research into these mutual, pulse-inversion propagation dynamics may address open scientific questions and pave the way toward simple, compact fiber sources that produce high-energy, sub-30-fs pulses.Background Several reports on epidemiological and clinical features of the 2019 coronavirus disease (COVID-19) have been published. However, mortality and morbidity analyses, important for better understanding the pathogenesis of this disease, are scarce. We examine the clinical and laboratory features of 14 patients who died of COVID-19. Methods The cohort consisted of 11 male and 3 female patients, with 9 patients aged 70 years or above, and nearly all had underlying diseases. Results Fever with bilateral pneumonia was the main manifestation. Most patients had consolidations combined with ground glass opacity (GGO) on chest computed tomography scan. Laboratory tests showed lymphocytopenia in 10 patients, high blood glucose in 11, GGT in 5 of the 14 patients, and high LDH in 5 of 6 patients tested. In addition, this cohort had high level of cytokines such as interleukin-6 in all 8 patients tested. Conclusions The clinical and laboratory parameters in the cohort of fatal cases may be incorporated into future clinical prognosis models and will be of help in understanding the pathogenesis of this disease.While spontaneous yawning is common across all vertebrate classes, contagious yawning is less common and has been observed only in a few species of social animals. Interspecific contagious yawning in response to yawning by humans has been observed only by chimpanzees and dogs. After confirming additional occurrences of intraspecific contagious yawning in a group of captive African elephants previously studied, we further investigated the potential for the same group of elephants to engage in interspecific contagious yawning with familiar human handlers. Ten captive African elephants, most of whom had been previously studied, were observed over 13 nights for evidence of intraspecific contagious yawning. Seven of these elephants were also involved in trials where familiar handlers performed staged yawns, as well as trials with staged non-yawning gapes, or trials with no yawns or gapes. Incorporating previously collected contagious yawning data, we describe nine instances of intraspecific contagious yawning in the elephants. Three of the seven elephants yawned contagiously in response to humans during the interspecific yawning trials. This is the first report of interspecific contagious yawning by elephants in response to yawns by familiar humans.High environmental temperature has strong adverse effects on poultry production, welfare, and sustainability and, thereby, constitutes one of the most challenging stressors. Although colossal information has been published on the effects of heat stress on poultry productivity and gut health, the fundamemntal mechanisms associated with heat stress responses and intestinal barrier function are still not well defined. The aim of the present study was, therefore, to determine the effects of acute (2 h) heat stress on growth performance, gut integrity, and intestinal expression of heat shock and tight junction proteins in slow- (broilers of the 1950's, ACRB), moderate- (broilers of 1990's, 95RAN), rapid-(modern broilers, MRB) growing birds, and their ancestor wild jungle fowl (JF). Heat stress exposure significantly increased the core body temperature of 95RAN and MRB chickens by ~0.5-1°C, but not that of JF and ACRB compared to their counterparts maintained at thermoneutral conditions. Heat stress also depressed feed intake and increased serum fluorescein isothiocyanate-dextran (FITC-D) levels (P less then 0.
    Infusions of epinephrine titrated to treat unstable hypotension, as well as potassium for severe hypokalemia may be required. Current scientific evidence does not support treatment or prophylactic use of these agents for COVID-19 disease. Regulatory and public health authorities recognize that CQ/HCQ may offer little clinical benefit and only add risk requiring further investigation before wider public distribution.The "4E" approach to cognition argues that cognition does not occur solely in the head, but is also embodied, embedded, enacted, or extended by way of extra-cranial processes and structures. Though very much in vogue, 4E cognition has received relatively few critical evaluations. By reflecting on two recent collections, this article reviews the 4E paradigm with a view to assessing its strengths and weaknesses.Research consortia play a key role in our understanding of how environmental exposures influence health and wellbeing, especially in the case of catastrophic events such as the Deepwater Horizon oil spill. A common challenge that prevents the optimal use of these data is the difficulty of harmonizing data regarding the environmental exposures and health effects across the studies within and among consortia. A review of the measures used by members of the Deepwater Horizon Research Consortia highlights the challenges associated with balancing timely implementation of a study to support disaster relief with optimizing the long-term value of the data. The inclusion of common, standard measures at the study design phase and a priori discussions regarding harmonization of study-specific measures among consortia members are key to overcoming this challenge. As more resources become available to support the use of standard measures, researchers now have the tools needed to rapidly coordinate their studies without compromising research focus or timely completion of the original study goals.Ultrafast lasers are becoming increasingly widespread in science and industry alike. Fiber-based ultrafast laser sources are especially attractive because of their compactness, alignment-free setups, and potentially low cost. https://www.selleckchem.com/products/ITF2357(Givinostat).html However, confining short pulses within a fiber core leads to high intensities, which drives a host of nonlinear effects. While these phenomena and their interactions greatly complicate the design of such systems, they can also provide opportunities for engineering new capabilities. Here, we report a new fiber amplification regime distinguished by the use of a dynamically evolving gain spectrum as a degree of freedom as a pulse experiences nonlinear spectral broadening, absorption and amplification actively reshape both the pulse and the gain spectrum itself. The dynamic co-evolution of the field and excited-state populations supports pulses that can broaden spectrally by almost two orders of magnitude and well beyond the gain bandwidth, while remaining cleanly compressible to their sub-50-fs transform limit. Theory and experiments provide evidence that a nonlinear attractor underlies the management of the nonlinearity by the gain. Further research into these mutual, pulse-inversion propagation dynamics may address open scientific questions and pave the way toward simple, compact fiber sources that produce high-energy, sub-30-fs pulses.Background Several reports on epidemiological and clinical features of the 2019 coronavirus disease (COVID-19) have been published. However, mortality and morbidity analyses, important for better understanding the pathogenesis of this disease, are scarce. We examine the clinical and laboratory features of 14 patients who died of COVID-19. Methods The cohort consisted of 11 male and 3 female patients, with 9 patients aged 70 years or above, and nearly all had underlying diseases. Results Fever with bilateral pneumonia was the main manifestation. Most patients had consolidations combined with ground glass opacity (GGO) on chest computed tomography scan. Laboratory tests showed lymphocytopenia in 10 patients, high blood glucose in 11, GGT in 5 of the 14 patients, and high LDH in 5 of 6 patients tested. In addition, this cohort had high level of cytokines such as interleukin-6 in all 8 patients tested. Conclusions The clinical and laboratory parameters in the cohort of fatal cases may be incorporated into future clinical prognosis models and will be of help in understanding the pathogenesis of this disease.While spontaneous yawning is common across all vertebrate classes, contagious yawning is less common and has been observed only in a few species of social animals. Interspecific contagious yawning in response to yawning by humans has been observed only by chimpanzees and dogs. After confirming additional occurrences of intraspecific contagious yawning in a group of captive African elephants previously studied, we further investigated the potential for the same group of elephants to engage in interspecific contagious yawning with familiar human handlers. Ten captive African elephants, most of whom had been previously studied, were observed over 13 nights for evidence of intraspecific contagious yawning. Seven of these elephants were also involved in trials where familiar handlers performed staged yawns, as well as trials with staged non-yawning gapes, or trials with no yawns or gapes. Incorporating previously collected contagious yawning data, we describe nine instances of intraspecific contagious yawning in the elephants. Three of the seven elephants yawned contagiously in response to humans during the interspecific yawning trials. This is the first report of interspecific contagious yawning by elephants in response to yawns by familiar humans.High environmental temperature has strong adverse effects on poultry production, welfare, and sustainability and, thereby, constitutes one of the most challenging stressors. Although colossal information has been published on the effects of heat stress on poultry productivity and gut health, the fundamemntal mechanisms associated with heat stress responses and intestinal barrier function are still not well defined. The aim of the present study was, therefore, to determine the effects of acute (2 h) heat stress on growth performance, gut integrity, and intestinal expression of heat shock and tight junction proteins in slow- (broilers of the 1950's, ACRB), moderate- (broilers of 1990's, 95RAN), rapid-(modern broilers, MRB) growing birds, and their ancestor wild jungle fowl (JF). Heat stress exposure significantly increased the core body temperature of 95RAN and MRB chickens by ~0.5-1°C, but not that of JF and ACRB compared to their counterparts maintained at thermoneutral conditions. Heat stress also depressed feed intake and increased serum fluorescein isothiocyanate-dextran (FITC-D) levels (P less then 0.
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  • In Xenopus laevis, the tadpole stage is characterized by three forms-those occurring before the initiation of limb development, those covering limb development, and those encompassing metamorphosis. Maximal tadpole growth, especially during the second form, is critically dependent on good husbandry practices. Here we describe a protocol for raising Xenopus laevis tadpoles through to adulthood. Each step may need to be modified depending on the aquaria used and local conditions. © 2021 Cold Spring Harbor Laboratory Press.Dhurrin is the most abundant cyanogenic glucoside found in sorghum spp. (Sorghum bicolor) where it plays a key role in chemical defence by releasing toxic hydrogen cyanide upon tissue disruption. Besides this well-established function, there is strong evidence that dhurrin plays additional roles, e.g. as a transport and storage form of nitrogen, released via endogenous recycling pathways. However, knowledge about how, when and why dhurrin is endogenously metabolized is limited. We combined targeted metabolite profiling with matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry imaging (MSI) to investigate accumulation of dhurrin, its recycling products and key general metabolites in four different sorghum lines during 72 h of grain imbibition, germination and early seedling development, as well as the spatial distribution of these metabolites in two of the lines. Little or no dhurrin or recycling products were present in the dry grain, but their de novo biosynthesis started immediately after water uptake. Dhurrin accumulation increased rapidly within the first 24 h in parallel with an increase in free amino acids, a key event in seed germination. The trajectories and final concentrations of dhurrin, the recycling products and free amino acids reached within the experimental period were dependent on genotype. MALDI-MSI demonstrated that dhurrin primarily accumulated in the germinating embryo, confirming its function in protecting the emerging tissue against herbivory. The dhurrin recycling products, however, were mainly located in the scutellum and/or pericarp/seed coat region, suggesting unknown key functions in germination. https://www.selleckchem.com/products/zidesamtinib.html copyright, serif 2020 American Society of Plant Biologists. All rights reserved.Auxin is a crucial plant growth regulator. Forward genetic screens for auxin-related mutants have led to the identification of key genes involved in auxin biosynthesis, transport, and signaling. Loss-of-function mutations in genes involved in glucosinolate biosynthesis, a metabolically-related route that produces defense compounds, result in auxin overproduction. We identified an allelic series of fertile, hypomorphic Arabidopsis thaliana mutants for the essential glucosinolate biosynthetic gene ROOTY (RTY) that exhibit a range of phenotypic defects characteristic of enhanced auxin production. Genetic characterization of these lines uncovered phenotypic suppression by cyp79b2 cyp79b3, wei2, and wei7 mutations and revealed the phenomenon of interallelic complementation in several RTY transheterozygotes. Structural modeling of RTY elucidated the relationships between structure and function in the RTY homo- and heterodimers, and unveiled the likely structural basis of interallelic complementation. This work underscores the importance of employing true null mutants in genetic complementation studies. copyright, serif 2020 American Society of Plant Biologists. All rights reserved.Several reports have been published recently demonstrating a beneficial effect of epidermal growth factor receptor (EGFR) inhibitors in improving pathological and behavioral conditions in neurodegenerative diseases (NDDs) such as Alzheimer's disease (AD) and Amyotrophic Lateral Sclerosis (ALS) as well as the brain and spinal cord injuries (SCI). Despite successful therapeutics effects of EGFR inhibition in these pathological conditions, there is still no report of proof-of-concept studies in well-characterized animal models using recently developed Blood-Brain-Barrier (BBB) penetrating EGFR inhibitors which is due to previous conflicting reports concerning the level of EGFR or activated EGFR in normal and pathological conditions which caused target engagement a concern in any future EGFR inhibition therapy. In this review, the level of EGFR expression and activation in developing CNS compared to adult CNS will be explained as well as how neuronal injury or pathological conditions especially inflammation and amyloid fibrils induce reactive astrocytes leading to increase in the expression and activation of EGFR and finally neurodegeneration. Furthermore, in this review, we will discuss two main molecular mechanisms that can be proposed as neuroprotective effects of EGFR inhibition in these pathological conditions. We will also review the recent advances in the development of BBB- penetrating EGFR inhibitors in cancer therapy, which may eventually be repositioned for NDDs and SCI therapy in the future. SIGNIFICANCE STATEMENT Based on lessons from applications of EGFR inhibitor in oncology, it is concluded that EGFR inhibitors can be beneficial in treatment of neurodegenerative diseases and spinal cord injuries. They carry their therapeutic potentials through induction of autophagy and attenuation of reactive astrocytes. The American Society for Pharmacology and Experimental Therapeutics.BACKGROUND Immunogenicity of cancer vaccines is impacted by adjuvants and schedule, but systematic assessments of their effects have not been performed. Montanide ISA-51, an incomplete Freund's adjuvant (IFA), is used in many vaccine trials, but concerns have been raised about negative effects in murine studies. We found in humans that IFA enhances systemic immune responses and that repeat vaccination at one site (same site vaccination (SSV)) creates tertiary lymphoid structures (TLS) in the vaccine site microenvironment (VSME). We hypothesized that vaccination with peptides+IFA+pICLC or SSV×3 with peptides in IFA would create an immunogenic milieu locally at the VSME, with activated dendritic cells (DC), TLS-associated chemokines and a Th1-dominant VSME. METHODS Biopsies of the VSME were obtained from participants on two clinical trials who were immunized with multiple melanoma peptides (MELITAC 12.1) in adjuvants comprising IFA and/or the TLR3-agonist pICLC. Biopsies were obtained either a week after one vaccine or a week after SSV×3.
    In Xenopus laevis, the tadpole stage is characterized by three forms-those occurring before the initiation of limb development, those covering limb development, and those encompassing metamorphosis. Maximal tadpole growth, especially during the second form, is critically dependent on good husbandry practices. Here we describe a protocol for raising Xenopus laevis tadpoles through to adulthood. Each step may need to be modified depending on the aquaria used and local conditions. © 2021 Cold Spring Harbor Laboratory Press.Dhurrin is the most abundant cyanogenic glucoside found in sorghum spp. (Sorghum bicolor) where it plays a key role in chemical defence by releasing toxic hydrogen cyanide upon tissue disruption. Besides this well-established function, there is strong evidence that dhurrin plays additional roles, e.g. as a transport and storage form of nitrogen, released via endogenous recycling pathways. However, knowledge about how, when and why dhurrin is endogenously metabolized is limited. We combined targeted metabolite profiling with matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry imaging (MSI) to investigate accumulation of dhurrin, its recycling products and key general metabolites in four different sorghum lines during 72 h of grain imbibition, germination and early seedling development, as well as the spatial distribution of these metabolites in two of the lines. Little or no dhurrin or recycling products were present in the dry grain, but their de novo biosynthesis started immediately after water uptake. Dhurrin accumulation increased rapidly within the first 24 h in parallel with an increase in free amino acids, a key event in seed germination. The trajectories and final concentrations of dhurrin, the recycling products and free amino acids reached within the experimental period were dependent on genotype. MALDI-MSI demonstrated that dhurrin primarily accumulated in the germinating embryo, confirming its function in protecting the emerging tissue against herbivory. The dhurrin recycling products, however, were mainly located in the scutellum and/or pericarp/seed coat region, suggesting unknown key functions in germination. https://www.selleckchem.com/products/zidesamtinib.html copyright, serif 2020 American Society of Plant Biologists. All rights reserved.Auxin is a crucial plant growth regulator. Forward genetic screens for auxin-related mutants have led to the identification of key genes involved in auxin biosynthesis, transport, and signaling. Loss-of-function mutations in genes involved in glucosinolate biosynthesis, a metabolically-related route that produces defense compounds, result in auxin overproduction. We identified an allelic series of fertile, hypomorphic Arabidopsis thaliana mutants for the essential glucosinolate biosynthetic gene ROOTY (RTY) that exhibit a range of phenotypic defects characteristic of enhanced auxin production. Genetic characterization of these lines uncovered phenotypic suppression by cyp79b2 cyp79b3, wei2, and wei7 mutations and revealed the phenomenon of interallelic complementation in several RTY transheterozygotes. Structural modeling of RTY elucidated the relationships between structure and function in the RTY homo- and heterodimers, and unveiled the likely structural basis of interallelic complementation. This work underscores the importance of employing true null mutants in genetic complementation studies. copyright, serif 2020 American Society of Plant Biologists. All rights reserved.Several reports have been published recently demonstrating a beneficial effect of epidermal growth factor receptor (EGFR) inhibitors in improving pathological and behavioral conditions in neurodegenerative diseases (NDDs) such as Alzheimer's disease (AD) and Amyotrophic Lateral Sclerosis (ALS) as well as the brain and spinal cord injuries (SCI). Despite successful therapeutics effects of EGFR inhibition in these pathological conditions, there is still no report of proof-of-concept studies in well-characterized animal models using recently developed Blood-Brain-Barrier (BBB) penetrating EGFR inhibitors which is due to previous conflicting reports concerning the level of EGFR or activated EGFR in normal and pathological conditions which caused target engagement a concern in any future EGFR inhibition therapy. In this review, the level of EGFR expression and activation in developing CNS compared to adult CNS will be explained as well as how neuronal injury or pathological conditions especially inflammation and amyloid fibrils induce reactive astrocytes leading to increase in the expression and activation of EGFR and finally neurodegeneration. Furthermore, in this review, we will discuss two main molecular mechanisms that can be proposed as neuroprotective effects of EGFR inhibition in these pathological conditions. We will also review the recent advances in the development of BBB- penetrating EGFR inhibitors in cancer therapy, which may eventually be repositioned for NDDs and SCI therapy in the future. SIGNIFICANCE STATEMENT Based on lessons from applications of EGFR inhibitor in oncology, it is concluded that EGFR inhibitors can be beneficial in treatment of neurodegenerative diseases and spinal cord injuries. They carry their therapeutic potentials through induction of autophagy and attenuation of reactive astrocytes. The American Society for Pharmacology and Experimental Therapeutics.BACKGROUND Immunogenicity of cancer vaccines is impacted by adjuvants and schedule, but systematic assessments of their effects have not been performed. Montanide ISA-51, an incomplete Freund's adjuvant (IFA), is used in many vaccine trials, but concerns have been raised about negative effects in murine studies. We found in humans that IFA enhances systemic immune responses and that repeat vaccination at one site (same site vaccination (SSV)) creates tertiary lymphoid structures (TLS) in the vaccine site microenvironment (VSME). We hypothesized that vaccination with peptides+IFA+pICLC or SSV×3 with peptides in IFA would create an immunogenic milieu locally at the VSME, with activated dendritic cells (DC), TLS-associated chemokines and a Th1-dominant VSME. METHODS Biopsies of the VSME were obtained from participants on two clinical trials who were immunized with multiple melanoma peptides (MELITAC 12.1) in adjuvants comprising IFA and/or the TLR3-agonist pICLC. Biopsies were obtained either a week after one vaccine or a week after SSV×3.
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  • Blueberries are distinguished by their purple-blue fruit color, which develops during ripening and is derived from a characteristic composition of flavonoid-derived anthocyanin pigments. The production of anthocyanins is confined to fruit skin, leaving the colorless fruit flesh devoid of these compounds. By linking accumulation patterns of phenolic metabolites with gene transcription in Northern Highbush (Vaccinium corymbosum) and Rabbiteye (Vaccinium virgatum) blueberry, we investigated factors limiting anthocyanin production in berry flesh. We find that flavonoid production was generally lower in fruit flesh compared with skin and concentrations further declined during maturation. A common set of structural genes was identified across both species, indicating that tissue-specific flavonoid biosynthesis was dependent on co-expression of multiple pathway genes and limited by the phenylpropanoid pathway in combination with CHS, F3H, and ANS as potential pathway bottlenecks. While metabolite concentrations were comparable between the blueberry genotypes when fully ripe, the anthocyanin composition was distinct and depended on the degree of hydroxylation/methoxylation of the anthocyanidin moiety in combination with genotype-specific glycosylation patterns. Co-correlation analysis of phenolic metabolites with pathway structural genes revealed characteristic isoforms of O-methyltransferases and UDP-glucoseflavonoid-3-O-glycosyltransferase that were likely to modulate anthocyanin composition. Finally, we identified candidate transcriptional regulators that were co-expressed with structural genes, including the activators MYBA, MYBPA1, and bHLH2 together with the repressor MYBC2, which suggested an interdependent role in anthocyanin regulation.The MELiSSA Pilot Plant (MPP) is testing in terrestrial conditions regenerative life support technologies for human exploration in Space. One of its components is a controlled Higher Plant Chamber (HPC) accommodating hydroponic plant cultures. It consists of a 9 m3 single closed growth chamber providing adequate environmental conditions for growing plants, enabling the production of food, water and oxygen for the crew. A critical aspect for a reliable HPC performance is to achieve homogeneous air distribution. The initial experiment carried out in the MPP with lettuce as salad crop, showed uneven plant growth throughout the HPC, which was attributed to inadequate air distribution due to non-homogeneous air velocity profile along the inlet-vents. After a detailed computational fluid dynamics (CFD) analysis, the heating, ventilation, and air conditioning subsystem of the HPC was upgraded and a new experiment was carried out in optimized air flow conditions. https://www.selleckchem.com/products/sn-38.html Nine-day seedlings of lettuce cultivar "Grand Rapids" were transplanted into the HPC and harvested at the end of the growing cycle, where shoot fresh weight, dry biomass, and shoot mineral composition were analyzed. During the experiment, the environmental control system performed remarkably well based on the biometric measurements as well as the mineral composition leading to a vast homogeneous growth. Overall, the results demonstrated the beneficial effect of an adequate air distribution system in HPCs and the effectiveness of CFD-analysis to design properly the gas distribution. The obtained results are of high relevance for life support systems in space involving plants growth.Soil radio-cesium (Cs) contamination caused by nuclear accidents is a major public concern. In this review, we presented the behavior of radio-Cs in soils, the relationship between Cs+ and potassium (K) ion uptake from soils, and the Cs+ uptake model proposed previously. Finally, we introduced the newly elucidated mechanism of Cs+ uptake in rice plants and compared it with the previously proposed Cs+ uptake model. Cs is a trace element in soil. It is toxic to plants when absorbed at high concentrations, although this rarely occurs under normal environmental conditions. Nevertheless, radio-Cs released during nuclear weapon tests or nuclear power plant accidents is absorbed by plants, thus entering the food chain. As Cs+ strongly binds to the frayed edge sites of illitic clays in soil, it is hardly moved by the infiltration of rainwater. However, plants have a strong ability for inorganic ions uptake, causing re-diffusion of radio-Cs+ into ecosystems and radioactive contamination of food. It is hypothesized tharatio of HAK and VIC channels in Cs uptake, these results are consistent with the conventional model.Understanding the temporal and spatial patterns of soil water extraction and their impacts on growth response of winter wheat to deficit subsurface drip irrigation (SDI) conditions is critical for managing water scarcity and stabilizing yield. A field experiment was conducted from 2016 to 2018 involving five SDI amounts 0.25, 0.4, 0.6, 0.8, and 1.0 ETc, representing 25, 40, 60, 80, and 100% of crop evapotranspiration (ETc), respectively. The results showed that the 0.6 ETc treatment significantly increased soil water extraction from 40-80 and 80-140-cm from jointing to maturity as compared to the 1.0 ETc treatment. Whereas the 0.8 ETc treatment significantly increased soil water extraction from 80-140-cm deep soil from flowering to maturity in the first growing season. The crop was most water-stressed under the 0.25 and 0.4 ETc treatments, thus extracted more soil water from 0-140-cm soil profile. However, both treatments exhibited minimum plant tillers, lowest leaf water content, leaf area index (LAI), photosynthetic rate (P n ), and transpiration rate (T r ) as well as grain yield. All these parameters, except for leaf water content, P n after the flowering stage, and grain productivity, were also reduced in the 0.6 ETc treatment than the 1.0 ETc treatment. The differences between the 0.8 and 1.0 ETc treatments were minor in terms of plant height, LAI, spike number, P n and T r , but infertile tillers were fewer in the 0.8 ETc treatment. We obtained high yield from the 0.8 ETc treatment, and the 0.6ETc treatment resulted in the highest harvest index with improved WUE than other treatments. Integrating deficit irrigation into SDI can save water in winter wheat production in water-limited regions, which can not only enhance soil water extraction from deep soil layers, but also sustained yield by stimulating crop growth. Therefore, a deficit SDI system would be used to conserve water in water-limited regions.
    Blueberries are distinguished by their purple-blue fruit color, which develops during ripening and is derived from a characteristic composition of flavonoid-derived anthocyanin pigments. The production of anthocyanins is confined to fruit skin, leaving the colorless fruit flesh devoid of these compounds. By linking accumulation patterns of phenolic metabolites with gene transcription in Northern Highbush (Vaccinium corymbosum) and Rabbiteye (Vaccinium virgatum) blueberry, we investigated factors limiting anthocyanin production in berry flesh. We find that flavonoid production was generally lower in fruit flesh compared with skin and concentrations further declined during maturation. A common set of structural genes was identified across both species, indicating that tissue-specific flavonoid biosynthesis was dependent on co-expression of multiple pathway genes and limited by the phenylpropanoid pathway in combination with CHS, F3H, and ANS as potential pathway bottlenecks. While metabolite concentrations were comparable between the blueberry genotypes when fully ripe, the anthocyanin composition was distinct and depended on the degree of hydroxylation/methoxylation of the anthocyanidin moiety in combination with genotype-specific glycosylation patterns. Co-correlation analysis of phenolic metabolites with pathway structural genes revealed characteristic isoforms of O-methyltransferases and UDP-glucoseflavonoid-3-O-glycosyltransferase that were likely to modulate anthocyanin composition. Finally, we identified candidate transcriptional regulators that were co-expressed with structural genes, including the activators MYBA, MYBPA1, and bHLH2 together with the repressor MYBC2, which suggested an interdependent role in anthocyanin regulation.The MELiSSA Pilot Plant (MPP) is testing in terrestrial conditions regenerative life support technologies for human exploration in Space. One of its components is a controlled Higher Plant Chamber (HPC) accommodating hydroponic plant cultures. It consists of a 9 m3 single closed growth chamber providing adequate environmental conditions for growing plants, enabling the production of food, water and oxygen for the crew. A critical aspect for a reliable HPC performance is to achieve homogeneous air distribution. The initial experiment carried out in the MPP with lettuce as salad crop, showed uneven plant growth throughout the HPC, which was attributed to inadequate air distribution due to non-homogeneous air velocity profile along the inlet-vents. After a detailed computational fluid dynamics (CFD) analysis, the heating, ventilation, and air conditioning subsystem of the HPC was upgraded and a new experiment was carried out in optimized air flow conditions. https://www.selleckchem.com/products/sn-38.html Nine-day seedlings of lettuce cultivar "Grand Rapids" were transplanted into the HPC and harvested at the end of the growing cycle, where shoot fresh weight, dry biomass, and shoot mineral composition were analyzed. During the experiment, the environmental control system performed remarkably well based on the biometric measurements as well as the mineral composition leading to a vast homogeneous growth. Overall, the results demonstrated the beneficial effect of an adequate air distribution system in HPCs and the effectiveness of CFD-analysis to design properly the gas distribution. The obtained results are of high relevance for life support systems in space involving plants growth.Soil radio-cesium (Cs) contamination caused by nuclear accidents is a major public concern. In this review, we presented the behavior of radio-Cs in soils, the relationship between Cs+ and potassium (K) ion uptake from soils, and the Cs+ uptake model proposed previously. Finally, we introduced the newly elucidated mechanism of Cs+ uptake in rice plants and compared it with the previously proposed Cs+ uptake model. Cs is a trace element in soil. It is toxic to plants when absorbed at high concentrations, although this rarely occurs under normal environmental conditions. Nevertheless, radio-Cs released during nuclear weapon tests or nuclear power plant accidents is absorbed by plants, thus entering the food chain. As Cs+ strongly binds to the frayed edge sites of illitic clays in soil, it is hardly moved by the infiltration of rainwater. However, plants have a strong ability for inorganic ions uptake, causing re-diffusion of radio-Cs+ into ecosystems and radioactive contamination of food. It is hypothesized tharatio of HAK and VIC channels in Cs uptake, these results are consistent with the conventional model.Understanding the temporal and spatial patterns of soil water extraction and their impacts on growth response of winter wheat to deficit subsurface drip irrigation (SDI) conditions is critical for managing water scarcity and stabilizing yield. A field experiment was conducted from 2016 to 2018 involving five SDI amounts 0.25, 0.4, 0.6, 0.8, and 1.0 ETc, representing 25, 40, 60, 80, and 100% of crop evapotranspiration (ETc), respectively. The results showed that the 0.6 ETc treatment significantly increased soil water extraction from 40-80 and 80-140-cm from jointing to maturity as compared to the 1.0 ETc treatment. Whereas the 0.8 ETc treatment significantly increased soil water extraction from 80-140-cm deep soil from flowering to maturity in the first growing season. The crop was most water-stressed under the 0.25 and 0.4 ETc treatments, thus extracted more soil water from 0-140-cm soil profile. However, both treatments exhibited minimum plant tillers, lowest leaf water content, leaf area index (LAI), photosynthetic rate (P n ), and transpiration rate (T r ) as well as grain yield. All these parameters, except for leaf water content, P n after the flowering stage, and grain productivity, were also reduced in the 0.6 ETc treatment than the 1.0 ETc treatment. The differences between the 0.8 and 1.0 ETc treatments were minor in terms of plant height, LAI, spike number, P n and T r , but infertile tillers were fewer in the 0.8 ETc treatment. We obtained high yield from the 0.8 ETc treatment, and the 0.6ETc treatment resulted in the highest harvest index with improved WUE than other treatments. Integrating deficit irrigation into SDI can save water in winter wheat production in water-limited regions, which can not only enhance soil water extraction from deep soil layers, but also sustained yield by stimulating crop growth. Therefore, a deficit SDI system would be used to conserve water in water-limited regions.
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  • Stem cells are widely explored in regenerative medicine as a source to produce diverse cell types. Despite the wide usage of stem cells like mesenchymal stem cells (****) and induced pluripotent stem cells (iPSCs), there is a lack of robust methods to rapidly discern the phenotypic and functional heterogeneity of stem cells. The organization of actin cytoskeleton has been previously used to discern divergent stem cell differentiation pathways. In this paper, we highlight the versatility of a cell profiling method for actin turnover dynamics. Actin filaments in live stem cells are labeled using SiR-actin, a cell permeable fluorogenic probe, to determine the endogenous actin turnover. Live ****imaging after days of induction successfully demonstrated lineage specific change in actin turnover. Next, we highlighted the differences in the cellular heterogeneity of actin dynamics during adipogenic or osteogenic ****differentiation. Next, we applied the method to differentiating iPSCs in culture, and detected a progressive slowdown in actin turnover during differentiation upon stimulation with neural or cardiac media. Finally, as a proof of concept, the actin dynamic profiling was used to isolate **** via flow cytometry prior to sorting into three distinct sub-populations with low, intermediate or high actin dynamics. A greater fraction of **** with more rapid actin dynamics demonstrated increased inclination for adipogenesis, whereas, slower actin dynamics correlated with increased osteogenesis. Together, these results show that actin turnover can serve as a versatile biomarker to not only track cellular phenotypic heterogeneity but also harvest live cells with potential for differential phenotypic fates.Physiologically-based toxicokinetic (PBTK) models are important tools for in vitro to in vivo or inter-species extrapolations in health risk assessment of foodborne and non-foodborne chemicals. Here we present a generic PBTK model implemented in the EuroMix toolbox, MCRA 9 and predict internal kinetics of nine chemicals (three endocrine disrupters, three liver steatosis inducers, and three developmental toxicants), in data-rich and data-poor conditions, when increasingly complex levels of parametrization are applied. At the first stage, only QSAR models were used to determine substance-specific parameters, then some parameter values were refined by estimates from substance-specific or high-throughput in vitro experiments. https://www.selleckchem.com/products/Dapagliflozin.html At the last stage, elimination or absorption parameters were calibrated based on available in vivo kinetic data. The results illustrate that parametrization plays a capital role in the output of the PBTK model, as it can change how chemicals are prioritized based on internal concentration factors. In data-poor situations, estimates can be far from observed values. In many cases of chronic exposure, the PBTK model can be summarized by an external to internal dose factor, and interspecies concentration factors can be used to perform interspecies extrapolation. We finally discuss the implementation and use of the model in the MCRA risk assessment platform.Oral delivery of poorly water-soluble drugs (PWSDs), which predominate the development pipeline, poses significant challenges. Weakly basic compounds, such as atazanavir, represent a critical class of PWSDs as even the administration of the crystalline solid may invoke supersaturation during gastric-intestinal transfer. The absorption advantage afforded by this supersaturated state can be offset by inherent metastability and a tendency to revert to the lower energy crystalline state. Therefore, it is important to understand the physiological factors that can affect crystallization to improve in vitro-in vivo predictiveness and to regulate inter-individual responses. The first aim of this study was to elucidate the influence of lyso-phosphatidylcholine (lyso-PC) and sodium oleate on crystallization, as the products of phosphatidylcholine (PC) hydrolysis and the major lipid components of human intestinal fluid (HIF) and updated fasted state simulated intestinal fluid version 3 (FaSSIF-V3). Secondly, as an indivle salt fraction when designing a biorelevant medium for supersaturating formulations. In vivo, inter-individual differences in the amount and types of bile acids and phospholipids present may influence the behaviour of supersaturating formulations.Purpose Membrane engineering has versatile applications in adoptive cell therapies, immune therapy or drug delivery. Incorporation of lipidated antibody-derived ligands into cells may enforce supraphysiological cell interactions that offer new therapeutic approaches. A challenge is the defined synthesis of lipidated ligands that effectively interact with such membranes. Methods Sortase-A was used to attach a PEGylated, dimyristyl lipid-anchor on single-domain antibodies (VHH). The membrane insertion was investigated on liposomal bilayers, myeloid-derived suppressor cells (MDSC) and T cells. Results The lipidated VHHs remodeled liposomal as well as cellular membranes. The VHH carrying liposomes were successfully targeted towards antigen-positive cells. MDSC and Tcells were both modified with lipidated VHHs as detected with an FITC-anti-llama antibody. Tcells that carried an anti-CD11b VHH showed cellular association in vitro with CD11b+Gr-1+ MDSC in a two-dimensional magnetic activated cell sorting / flow-cytometry assay. Conclusion The applied combination of chemoenzymatic ligation, PEGylated lipid anchors and single-domain antibodies delivers water-soluble and chemically defined lipidated ligands, which readily associate with liposomal and cellular membranes. This enables liposomal drug targeting and artificial cell-cell interactions. Hence, the presented concept for lipidation of single-domain antibodies is promising for further application in the field of drug delivery or cell-based therapies.Wound healing is a complex and costly public health problem that should be timely addressed to achieve a rapid and adequate tissue repair avoiding or even eliminating potential pathogenic infection. Chronic infected non-healing wounds represent a serious concern for health care systems. Efficient wound dressings with tailored therapy having the best response and highest safety margin for the management of chronic non-healing wounds are still needed. The use of novel wound dressing materials has emerged as a promising tool to fulfil these requirements. In this work, asymmetric electrospun polycaprolactone (PCL)-based nanofibers (NFs) were decorated with electrosprayed poly(lactic-co-glycolic acid) microparticles (PLGA MPs) containing the natural antibacterial compound thymol (THY) in order to obtain drug eluting antimicrobial dressings having sustained release. The synthesized dressings successfully inhibited the in vitro growth of Staphylococcus aureus ATCC 25923, showing also at the same doses cytocompatibility on human dermal fibroblasts and keratinocyte cultures after treatment for 24 h, which was not observed when using free thymol.
    Stem cells are widely explored in regenerative medicine as a source to produce diverse cell types. Despite the wide usage of stem cells like mesenchymal stem cells (MSCs) and induced pluripotent stem cells (iPSCs), there is a lack of robust methods to rapidly discern the phenotypic and functional heterogeneity of stem cells. The organization of actin cytoskeleton has been previously used to discern divergent stem cell differentiation pathways. In this paper, we highlight the versatility of a cell profiling method for actin turnover dynamics. Actin filaments in live stem cells are labeled using SiR-actin, a cell permeable fluorogenic probe, to determine the endogenous actin turnover. Live MSC imaging after days of induction successfully demonstrated lineage specific change in actin turnover. Next, we highlighted the differences in the cellular heterogeneity of actin dynamics during adipogenic or osteogenic MSC differentiation. Next, we applied the method to differentiating iPSCs in culture, and detected a progressive slowdown in actin turnover during differentiation upon stimulation with neural or cardiac media. Finally, as a proof of concept, the actin dynamic profiling was used to isolate MSCs via flow cytometry prior to sorting into three distinct sub-populations with low, intermediate or high actin dynamics. A greater fraction of MSCs with more rapid actin dynamics demonstrated increased inclination for adipogenesis, whereas, slower actin dynamics correlated with increased osteogenesis. Together, these results show that actin turnover can serve as a versatile biomarker to not only track cellular phenotypic heterogeneity but also harvest live cells with potential for differential phenotypic fates.Physiologically-based toxicokinetic (PBTK) models are important tools for in vitro to in vivo or inter-species extrapolations in health risk assessment of foodborne and non-foodborne chemicals. Here we present a generic PBTK model implemented in the EuroMix toolbox, MCRA 9 and predict internal kinetics of nine chemicals (three endocrine disrupters, three liver steatosis inducers, and three developmental toxicants), in data-rich and data-poor conditions, when increasingly complex levels of parametrization are applied. At the first stage, only QSAR models were used to determine substance-specific parameters, then some parameter values were refined by estimates from substance-specific or high-throughput in vitro experiments. https://www.selleckchem.com/products/Dapagliflozin.html At the last stage, elimination or absorption parameters were calibrated based on available in vivo kinetic data. The results illustrate that parametrization plays a capital role in the output of the PBTK model, as it can change how chemicals are prioritized based on internal concentration factors. In data-poor situations, estimates can be far from observed values. In many cases of chronic exposure, the PBTK model can be summarized by an external to internal dose factor, and interspecies concentration factors can be used to perform interspecies extrapolation. We finally discuss the implementation and use of the model in the MCRA risk assessment platform.Oral delivery of poorly water-soluble drugs (PWSDs), which predominate the development pipeline, poses significant challenges. Weakly basic compounds, such as atazanavir, represent a critical class of PWSDs as even the administration of the crystalline solid may invoke supersaturation during gastric-intestinal transfer. The absorption advantage afforded by this supersaturated state can be offset by inherent metastability and a tendency to revert to the lower energy crystalline state. Therefore, it is important to understand the physiological factors that can affect crystallization to improve in vitro-in vivo predictiveness and to regulate inter-individual responses. The first aim of this study was to elucidate the influence of lyso-phosphatidylcholine (lyso-PC) and sodium oleate on crystallization, as the products of phosphatidylcholine (PC) hydrolysis and the major lipid components of human intestinal fluid (HIF) and updated fasted state simulated intestinal fluid version 3 (FaSSIF-V3). Secondly, as an indivle salt fraction when designing a biorelevant medium for supersaturating formulations. In vivo, inter-individual differences in the amount and types of bile acids and phospholipids present may influence the behaviour of supersaturating formulations.Purpose Membrane engineering has versatile applications in adoptive cell therapies, immune therapy or drug delivery. Incorporation of lipidated antibody-derived ligands into cells may enforce supraphysiological cell interactions that offer new therapeutic approaches. A challenge is the defined synthesis of lipidated ligands that effectively interact with such membranes. Methods Sortase-A was used to attach a PEGylated, dimyristyl lipid-anchor on single-domain antibodies (VHH). The membrane insertion was investigated on liposomal bilayers, myeloid-derived suppressor cells (MDSC) and T cells. Results The lipidated VHHs remodeled liposomal as well as cellular membranes. The VHH carrying liposomes were successfully targeted towards antigen-positive cells. MDSC and Tcells were both modified with lipidated VHHs as detected with an FITC-anti-llama antibody. Tcells that carried an anti-CD11b VHH showed cellular association in vitro with CD11b+Gr-1+ MDSC in a two-dimensional magnetic activated cell sorting / flow-cytometry assay. Conclusion The applied combination of chemoenzymatic ligation, PEGylated lipid anchors and single-domain antibodies delivers water-soluble and chemically defined lipidated ligands, which readily associate with liposomal and cellular membranes. This enables liposomal drug targeting and artificial cell-cell interactions. Hence, the presented concept for lipidation of single-domain antibodies is promising for further application in the field of drug delivery or cell-based therapies.Wound healing is a complex and costly public health problem that should be timely addressed to achieve a rapid and adequate tissue repair avoiding or even eliminating potential pathogenic infection. Chronic infected non-healing wounds represent a serious concern for health care systems. Efficient wound dressings with tailored therapy having the best response and highest safety margin for the management of chronic non-healing wounds are still needed. The use of novel wound dressing materials has emerged as a promising tool to fulfil these requirements. In this work, asymmetric electrospun polycaprolactone (PCL)-based nanofibers (NFs) were decorated with electrosprayed poly(lactic-co-glycolic acid) microparticles (PLGA MPs) containing the natural antibacterial compound thymol (THY) in order to obtain drug eluting antimicrobial dressings having sustained release. The synthesized dressings successfully inhibited the in vitro growth of Staphylococcus aureus ATCC 25923, showing also at the same doses cytocompatibility on human dermal fibroblasts and keratinocyte cultures after treatment for 24 h, which was not observed when using free thymol.
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  • Our study supports a new concept that miR-148a is a regulator of (P)RR expression. https://www.selleckchem.com/products/PD-98059.html By reducing (P)RR abundance, miR-148a decreases LDLR protein abundance and consequently cellular LDL uptake.[This corrects the article DOI 10.1371/journal.pone.0054193.].Successful human colonizers such as Candida pathogens have evolved distinct strategies to survive and proliferate within the human host. These include sophisticated mechanisms to evade immune surveillance and adapt to constantly changing host microenvironments where nutrient limitation, pH fluctuations, oxygen deprivation, changes in temperature, or exposure to oxidative, nitrosative, and cationic stresses may occur. Here, we review the current knowledge and recent findings highlighting the remarkable ability of medically important Candida species to overcome a broad range of host-imposed constraints and how this directly affects their physiology and pathogenicity. We also consider the impact of these adaptation mechanisms on immune recognition, biofilm formation, and antifungal drug resistance, as these pathogens often exploit specific host constraints to establish a successful infection. Recent studies of adaptive responses to physiological niches have improved our understanding of the mechanisms established by fungal pathogens to evade the immune system and colonize the host, which may facilitate the design of innovative diagnostic tests and therapeutic approaches for Candida infections.Objective Lung transplantation remains the only curative treatment for end-stage lung disease, conferring a better survival for some IPF patients, but whether they should receive double lung transplantation (DLT) or single lung transplantation (SLT) is still controversial. The aim of this study was to determine which type of lung transplantation was more effective and relatively safe in IPF patients by meta-analysis. Methods Publications comparing overall survival (OS) or other perioperative characteristics between IPF patients undergoing SLT and DLT were selected from electronic databases. The hazard ratios (HRs) were abstracted or calculated to evaluate the survival outcome. Odds ratios (ORs) or mean differences (MDs) were used to compare the causes of death or perioperative parameters. A random-effect model was used to combine data. Heterogeneity was quantified by means of an I2 with 95% confidence interval (95% CI). The publication bias was estimated using the Eggers test with Begg's funnel plots. Results 16 studies with 17,872 IPF cases who met the inclusion criteria were included in this meta-analysis. SLT was associated with declined post-transplant FEV1% (MD = -15.37, 95% CI-22.28,-8.47; P0.05). Moreover, there was fewer deaths attributable to primary graft dysfunction in SLT recipients (OR = 0.31, 95% CI 0.2-0.48; P less then 0.001), while more patients with SLT died of malignancy (OR = 3.44, 95% CI 2.06-5.77; P less then 0.001). Conclusion Our findings suggest that DLT was associated with better postoperative pulmonary function, but there was no difference in long-term overall survival between patients undergoing DLT and SLT. However, further high-quality and large-scale studies are needed to confirm these findings.[This corrects the article DOI 10.1371/journal.pone.0231795.].[This corrects the article DOI 10.1371/journal.pone.0211032.].In an effort to mitigate the outbreak of COVID-19, many countries have imposed drastic lockdown, movement control or shelter in place orders on their residents. The effectiveness of these mitigation measures is highly dependent on cooperation and compliance of all members of society. The knowledge, attitudes and practices people hold toward the disease play an integral role in determining a society's readiness to accept behavioural change measures from health authorities. The aim of this study was to determine the knowledge levels, attitudes and practices toward COVID-19 among the Malaysian public. A cross-sectional online survey of 4,850 Malaysian residents was conducted between 27th March and 3rd April 2020. The survey instrument consisted of demographic characteristics, 13 items on knowledge, 3 items on attitudes and 3 items on practices, modified from a previously published questionnaire on COVID-19. Descriptive statistics, chi-square tests, t-tests and one-way analysis of variance (ANOVA) were conducted. The overall correct rate of the knowledge questionnaire was 80.5%. Most participants held positive attitudes toward the successful control of COVID-19 (83.1%), the ability of Malaysia to conquer the disease (95.9%) and the way the Malaysian government was handling the crisis (89.9%). Most participants were also taking precautions such as avoiding crowds (83.4%) and practising proper hand hygiene (87.8%) in the week before the movement control order started. However, the wearing of face masks was less common (51.2%). This survey is among the first to assess knowledge, attitudes and practice in response to the COVID-19 pandemic in Malaysia. The results highlight the importance of consistent messaging from health authorities and the government as well as the need for tailored health education programs to improve levels of knowledge, attitudes and practices.[This corrects the article DOI 10.1371/journal.pone.0232173.].Background Novel-coronavirus disease-2019 (COVID-19) is currently a pandemic and public health emergency of international concern, as avowed by the World Health Organization (WHO). Ethiopia has become one of the affected countries as of March 15, 2020. Objective This study aimed to assess the knowledge, perceptions, and practices among the Jimma University medical center (JUMC) visitors in Jimma town. Methods A cross-sectional study was conducted on 247 sampled visitors, from 20-24 March 2020. Consecutive sampling was used to recruit the participants. The study tools were adapted from WHO resources. The data were analyzed using the Statistical Package for Social Sciences (SPSS) version 20.0. Descriptive statistics were used to describe the status of knowledge, perception, and practices. Logistic regression was executed to assess the predictors of dominant preventive practices. Results Of the 247 respondents, 205 (83.0%) knew the main clinical symptoms of COVID-19. 72.0% knew that older people who have chronic illnesses are at high risk of developing a severe form of COVID-19.
    Our study supports a new concept that miR-148a is a regulator of (P)RR expression. https://www.selleckchem.com/products/PD-98059.html By reducing (P)RR abundance, miR-148a decreases LDLR protein abundance and consequently cellular LDL uptake.[This corrects the article DOI 10.1371/journal.pone.0054193.].Successful human colonizers such as Candida pathogens have evolved distinct strategies to survive and proliferate within the human host. These include sophisticated mechanisms to evade immune surveillance and adapt to constantly changing host microenvironments where nutrient limitation, pH fluctuations, oxygen deprivation, changes in temperature, or exposure to oxidative, nitrosative, and cationic stresses may occur. Here, we review the current knowledge and recent findings highlighting the remarkable ability of medically important Candida species to overcome a broad range of host-imposed constraints and how this directly affects their physiology and pathogenicity. We also consider the impact of these adaptation mechanisms on immune recognition, biofilm formation, and antifungal drug resistance, as these pathogens often exploit specific host constraints to establish a successful infection. Recent studies of adaptive responses to physiological niches have improved our understanding of the mechanisms established by fungal pathogens to evade the immune system and colonize the host, which may facilitate the design of innovative diagnostic tests and therapeutic approaches for Candida infections.Objective Lung transplantation remains the only curative treatment for end-stage lung disease, conferring a better survival for some IPF patients, but whether they should receive double lung transplantation (DLT) or single lung transplantation (SLT) is still controversial. The aim of this study was to determine which type of lung transplantation was more effective and relatively safe in IPF patients by meta-analysis. Methods Publications comparing overall survival (OS) or other perioperative characteristics between IPF patients undergoing SLT and DLT were selected from electronic databases. The hazard ratios (HRs) were abstracted or calculated to evaluate the survival outcome. Odds ratios (ORs) or mean differences (MDs) were used to compare the causes of death or perioperative parameters. A random-effect model was used to combine data. Heterogeneity was quantified by means of an I2 with 95% confidence interval (95% CI). The publication bias was estimated using the Eggers test with Begg's funnel plots. Results 16 studies with 17,872 IPF cases who met the inclusion criteria were included in this meta-analysis. SLT was associated with declined post-transplant FEV1% (MD = -15.37, 95% CI-22.28,-8.47; P0.05). Moreover, there was fewer deaths attributable to primary graft dysfunction in SLT recipients (OR = 0.31, 95% CI 0.2-0.48; P less then 0.001), while more patients with SLT died of malignancy (OR = 3.44, 95% CI 2.06-5.77; P less then 0.001). Conclusion Our findings suggest that DLT was associated with better postoperative pulmonary function, but there was no difference in long-term overall survival between patients undergoing DLT and SLT. However, further high-quality and large-scale studies are needed to confirm these findings.[This corrects the article DOI 10.1371/journal.pone.0231795.].[This corrects the article DOI 10.1371/journal.pone.0211032.].In an effort to mitigate the outbreak of COVID-19, many countries have imposed drastic lockdown, movement control or shelter in place orders on their residents. The effectiveness of these mitigation measures is highly dependent on cooperation and compliance of all members of society. The knowledge, attitudes and practices people hold toward the disease play an integral role in determining a society's readiness to accept behavioural change measures from health authorities. The aim of this study was to determine the knowledge levels, attitudes and practices toward COVID-19 among the Malaysian public. A cross-sectional online survey of 4,850 Malaysian residents was conducted between 27th March and 3rd April 2020. The survey instrument consisted of demographic characteristics, 13 items on knowledge, 3 items on attitudes and 3 items on practices, modified from a previously published questionnaire on COVID-19. Descriptive statistics, chi-square tests, t-tests and one-way analysis of variance (ANOVA) were conducted. The overall correct rate of the knowledge questionnaire was 80.5%. Most participants held positive attitudes toward the successful control of COVID-19 (83.1%), the ability of Malaysia to conquer the disease (95.9%) and the way the Malaysian government was handling the crisis (89.9%). Most participants were also taking precautions such as avoiding crowds (83.4%) and practising proper hand hygiene (87.8%) in the week before the movement control order started. However, the wearing of face masks was less common (51.2%). This survey is among the first to assess knowledge, attitudes and practice in response to the COVID-19 pandemic in Malaysia. The results highlight the importance of consistent messaging from health authorities and the government as well as the need for tailored health education programs to improve levels of knowledge, attitudes and practices.[This corrects the article DOI 10.1371/journal.pone.0232173.].Background Novel-coronavirus disease-2019 (COVID-19) is currently a pandemic and public health emergency of international concern, as avowed by the World Health Organization (WHO). Ethiopia has become one of the affected countries as of March 15, 2020. Objective This study aimed to assess the knowledge, perceptions, and practices among the Jimma University medical center (JUMC) visitors in Jimma town. Methods A cross-sectional study was conducted on 247 sampled visitors, from 20-24 March 2020. Consecutive sampling was used to recruit the participants. The study tools were adapted from WHO resources. The data were analyzed using the Statistical Package for Social Sciences (SPSS) version 20.0. Descriptive statistics were used to describe the status of knowledge, perception, and practices. Logistic regression was executed to assess the predictors of dominant preventive practices. Results Of the 247 respondents, 205 (83.0%) knew the main clinical symptoms of COVID-19. 72.0% knew that older people who have chronic illnesses are at high risk of developing a severe form of COVID-19.
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