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  • The slow-light phenomenon using a dielectric-metal-based plasmonic waveguide could be very useful in construction of terahertz buffers, storage devices, terahertz sensors, detectors, etc.In this paper, we present a simple and flexible non-interferometric method to generate various polarization singularity lattice fields. The proposed method is based on a double modulation technique that uses a single reflective spatial light modulator to generate different lattice structures consisting of V-point and C-point polarization singularities. The present technique is compact with respect to previous experimental realization techniques. Different structures having star and lemon fields are generated without altering the experimental setup. In addition, the same setup can be used to obtain different types of inhomogeneous fields embedded with isolated polarization singularities even of higher orders. The Stokes polarimetry method has been used to obtain the polarization distributions of generated fields, which are in good agreement with simulated results.Image sharpening algorithms used for phase retrieval to reconstruct images in digital holography are computationally intensive, requiring iterative virtual wavefront propagation and hill-climbing algorithms to optimize sharpness criteria. Recently, it was shown that minimum-variance wavefront prediction can be integrated with digital holography and image sharpening to significantly reduce the large number of costly sharpening iterations normally required to achieve near-optimal wavefront estimation [J. Opt. https://www.selleckchem.com/products/z-vad(oh)-fmk.html Soc. Am. A35, 923 (2018)JOAOD60740-323210.1364/JOSAA.35.000923]. This paper demonstrates further gains in computational efficiency with a new subspace sharpening method in conjunction with predictive dynamic digital holography for real-time applications. The method sharpens local regions of interest in an image plane by parallel independent wavefront estimation on reduced-dimension subspaces of the complex field in a pupil plane. Through wave-optics simulations, this paper shows that the new subspace method produces results comparable to those of conventional global and local sharpening, and that subspace wavefront estimation and sharpening coupled with wavefront prediction achieve orders-of-magnitude increases in processing speed.In this paper, a general methodology to study rigorous discontinuities in open waveguides is presented. It relies on a full vector description given by Maxwell's equations in the framework of the finite element method. The discontinuities are not necessarily small perturbations of the initial waveguide and can be very general, such as plasmonic inclusions of arbitrary shapes. The leaky modes of the invariant structure are first computed and then injected as incident fields in the full structure with obstacles using a scattered field approach. The resulting scattered field is finally projected on the modes of the invariant structure making use of their bi-orthogonality. The energy balance is discussed. Finally, the modes of open waveguides periodically structured along the propagation direction are computed. The relevant complex propagation constants are compared to the transmission obtained for a finite number of identical cells. The relevance and complementarity of the two approaches are highlighted on a numerical example encountered in infrared sensing. Open source models allowing us to retrieve most of the results of this paper are provided.A reformulation of the differential theory associated with fast Fourier factorization used for periodic diffractive structures is presented. The incorporation of a complex coordinate transformation in the propagation equations allows the modeling of semi-infinite open problems through an artificially periodized space. Hence, the outgoing wave conditions of an open structure must be satisfied. On the other hand, the excitation technique must be adjusted to adapt with guided structures. These modifications turn the differential theory into an aperiodic tool used with guided optical structure. Our method is verified through numerical results and comparisons with the aperiodic Fourier modal method showing enhanced convergence and accuracy, especially when complex-shaped photonic guided devices are considered.We propose and theoretically analyze a single-order diffractive optical element, termed binary sinusoidal multilayer grating (BSMG), to effectively suppress high-order diffractions while retaining high diffraction efficiency in the first order. The key idea is to integrate sinusoidal-shaped microstructures with high-reflectivity multilayer coatings. The dependence of the high-order diffraction property on the microstructure shape and multilayer coatings is investigated. Theoretical calculation reveals that the second-, third-, fourth-, and fifth-order diffraction efficiencies are as low as 0.01%. Strikingly, we show that first-order relative diffraction efficiency (the ratio between the intensity of the first diffraction order versus that of the reflected light) as high as 97.7% can be achieved. Thus, the proposed BSMG should be highly advantageous in future development and application of tender x-ray spectroscopy.A multilayer patterned graphene metamaterial composed of rectangular graphene, square graphene, and X-shaped graphene is proposed to achieve dual plasmon-induced transparency (PIT) at terahertz frequency. The coupled mode theory calculations are highly consistent with the finite-difference time-domain numerical results. Interestingly, a photoelectric switch has been realized, whose extinction ratio and modulation degree of amplitude can be 7.77 dB and 83.3% with the insertion loss of 7.2%. In addition, any dips can be modulated by tuning the Fermi levels of three graphene layers with minor or ignorable changes of the other two dips. The modulation degrees of frequency are 8.0%, 7.4% and 11.7%, respectively, which can be used to design a triple-mode frequency modulator. Moreover, the group index of the multilayer structure can be as high as 150. Therefore, it is reasonable to believe that a multifunctional device can be realized by the proposed structure.
    The slow-light phenomenon using a dielectric-metal-based plasmonic waveguide could be very useful in construction of terahertz buffers, storage devices, terahertz sensors, detectors, etc.In this paper, we present a simple and flexible non-interferometric method to generate various polarization singularity lattice fields. The proposed method is based on a double modulation technique that uses a single reflective spatial light modulator to generate different lattice structures consisting of V-point and C-point polarization singularities. The present technique is compact with respect to previous experimental realization techniques. Different structures having star and lemon fields are generated without altering the experimental setup. In addition, the same setup can be used to obtain different types of inhomogeneous fields embedded with isolated polarization singularities even of higher orders. The Stokes polarimetry method has been used to obtain the polarization distributions of generated fields, which are in good agreement with simulated results.Image sharpening algorithms used for phase retrieval to reconstruct images in digital holography are computationally intensive, requiring iterative virtual wavefront propagation and hill-climbing algorithms to optimize sharpness criteria. Recently, it was shown that minimum-variance wavefront prediction can be integrated with digital holography and image sharpening to significantly reduce the large number of costly sharpening iterations normally required to achieve near-optimal wavefront estimation [J. Opt. https://www.selleckchem.com/products/z-vad(oh)-fmk.html Soc. Am. A35, 923 (2018)JOAOD60740-323210.1364/JOSAA.35.000923]. This paper demonstrates further gains in computational efficiency with a new subspace sharpening method in conjunction with predictive dynamic digital holography for real-time applications. The method sharpens local regions of interest in an image plane by parallel independent wavefront estimation on reduced-dimension subspaces of the complex field in a pupil plane. Through wave-optics simulations, this paper shows that the new subspace method produces results comparable to those of conventional global and local sharpening, and that subspace wavefront estimation and sharpening coupled with wavefront prediction achieve orders-of-magnitude increases in processing speed.In this paper, a general methodology to study rigorous discontinuities in open waveguides is presented. It relies on a full vector description given by Maxwell's equations in the framework of the finite element method. The discontinuities are not necessarily small perturbations of the initial waveguide and can be very general, such as plasmonic inclusions of arbitrary shapes. The leaky modes of the invariant structure are first computed and then injected as incident fields in the full structure with obstacles using a scattered field approach. The resulting scattered field is finally projected on the modes of the invariant structure making use of their bi-orthogonality. The energy balance is discussed. Finally, the modes of open waveguides periodically structured along the propagation direction are computed. The relevant complex propagation constants are compared to the transmission obtained for a finite number of identical cells. The relevance and complementarity of the two approaches are highlighted on a numerical example encountered in infrared sensing. Open source models allowing us to retrieve most of the results of this paper are provided.A reformulation of the differential theory associated with fast Fourier factorization used for periodic diffractive structures is presented. The incorporation of a complex coordinate transformation in the propagation equations allows the modeling of semi-infinite open problems through an artificially periodized space. Hence, the outgoing wave conditions of an open structure must be satisfied. On the other hand, the excitation technique must be adjusted to adapt with guided structures. These modifications turn the differential theory into an aperiodic tool used with guided optical structure. Our method is verified through numerical results and comparisons with the aperiodic Fourier modal method showing enhanced convergence and accuracy, especially when complex-shaped photonic guided devices are considered.We propose and theoretically analyze a single-order diffractive optical element, termed binary sinusoidal multilayer grating (BSMG), to effectively suppress high-order diffractions while retaining high diffraction efficiency in the first order. The key idea is to integrate sinusoidal-shaped microstructures with high-reflectivity multilayer coatings. The dependence of the high-order diffraction property on the microstructure shape and multilayer coatings is investigated. Theoretical calculation reveals that the second-, third-, fourth-, and fifth-order diffraction efficiencies are as low as 0.01%. Strikingly, we show that first-order relative diffraction efficiency (the ratio between the intensity of the first diffraction order versus that of the reflected light) as high as 97.7% can be achieved. Thus, the proposed BSMG should be highly advantageous in future development and application of tender x-ray spectroscopy.A multilayer patterned graphene metamaterial composed of rectangular graphene, square graphene, and X-shaped graphene is proposed to achieve dual plasmon-induced transparency (PIT) at terahertz frequency. The coupled mode theory calculations are highly consistent with the finite-difference time-domain numerical results. Interestingly, a photoelectric switch has been realized, whose extinction ratio and modulation degree of amplitude can be 7.77 dB and 83.3% with the insertion loss of 7.2%. In addition, any dips can be modulated by tuning the Fermi levels of three graphene layers with minor or ignorable changes of the other two dips. The modulation degrees of frequency are 8.0%, 7.4% and 11.7%, respectively, which can be used to design a triple-mode frequency modulator. Moreover, the group index of the multilayer structure can be as high as 150. Therefore, it is reasonable to believe that a multifunctional device can be realized by the proposed structure.
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  • The water-soluble fullerenols are novel carbon-based nanomaterials with unique properties, which afford them with wide agricultural applications. Iron (Fe) deficiency is the most common and widespread nutrition disorder affecting plants. Foliar Fe treatments of plants have been carried out with solutions devoid of fullerenol. In this study, the role of fullerenol [C60(OH)22-24] in alleviation of Fe deficiency in Cucumis sativus (a Strategy I plant) via foliar fertilization was investigated. Cucumber plants were grown hydroponically, either with (Fe) or in Fe-free (-Fe) nutrient solution. The following foliar spray treatments were applied fullerenol at final concentrations of 1 (F1) and 10 (F10) mg L-1; Fe(II)SO4·7H2O; Fe(II)-EDTA (ethylenediaminetetraacetic acid); and Fe(II)-F1 and Fe(II)-F10. https://www.selleckchem.com/ The best used compound was a combination of Fe(II)-sulfate with fullerenol, especially Fe-F1. The addition of fullerenol to Fe(II)-sulfate solutions significantly increased leaf-active Fe (extracted by an Fe(II) chelator) and re-greening at the site of application. The fullerenol-induced mutual influences did not appear when fullerenol was sprayed alone, suggesting a beneficial role of Fe(II)-fullerenol interactions in the penetration of Fe(II) in the leaves and re-greening under Fe-limited conditions. The results are of importance to enhancing the potential of foliar Fe fertilization as the commonly used strategy for ameliorating Fe deficiency and improving crop yield and quality.In coronary artery disease (***), exercise intolerance with reduced oxygen uptake at peak exercise (VO2peak) is assumed to primarily reflect cardiovascular limitation. However, oxygen transport and utilization depends on an integrated organ response, to which the normal pulmonary system may influence overall capacity. This study aimed to investigate the associations between normal values of lung function measures and VO2peak in patients with exercise intolerance and ***. We hypothesized that forced expiratory lung volume in one second (FEV1), transfer factor of the lung for carbon monoxide (TLCO) and TLCO/alveolar volume (TLCO/VA) above lower limits of normal (LLN) are associated with VO2peak in these patients. We assessed patients with established *** (n = 93; 21 women) referred for evaluation due to exercise intolerance from primary care to a private specialist clinic in Norway. Lung function tests and cardiopulmonary exercise testing (CPET) were performed. Z-scores of FEV1, FEV1/forced vital capacity (FVC), TLCO and TLCO/VA were calculated using the Global Lung Function Initiative (GLI) software and LLN was defined as the fifth percentile (z = -1.645). Non-obstructive patients, defined by both FEV1 and FEV1/FVC above LLN, were assessed. The associations of FEV1Z-score, TLCOZ-score and TLCO/VAZ-score above LLN with VO2peak were investigated using linear regression models. Mean VO2peak ± standard deviation (SD) was 23.8 ± 6.4 ml/kg/min in men and 19.7 ± 4.4 ml/kg/min in women. On average, one SD increase in FEV1, TLCO and TLCO/VA were associated with 1.4 (95% CI 0.2, 2.6), 2.6 (95% CI 1.2, 4.0) and 1.3 (95% CI 0.2, 2.5) ml/kg/min higher VO2peak, respectively. In non-obstructive patients with exercise intolerance and ***, FEV1, TLCO and TLCO/VA above LLN are positively associated with VO2peak. This may imply a clinically significant influence of normal lung function on exercise capacity in these patients.BACKGROUND Astodrimer Gel contains a novel dendrimer intended to treat and prevent bacterial vaginosis. We assessed the efficacy and safety of Astodrimer Gel for treatment of bacterial vaginosis. METHODS 132 women with bacterial vaginosis were randomized 1111 to Astodrimer 0.5% (N = 34), 1% (N = 33), or 3% (N = 32) Gel or hydroxyethyl cellulose placebo gel (N = 33) at a dose of 5 g vaginally once daily for 7 days at 6 centers in the United States. The primary endpoint was clinical cure (no bacterial vaginosis vaginal discharge and no more than one of 1) vaginal pH ≥4.5; 2) ≥20% clue cells; or 3) positive whiff test) at study days 21-30. Secondary analyses included clinical cure at study days 9-12, patient-reported symptoms, acceptability and adverse events. RESULTS The Astodrimer 1% Gel dose was superior to placebo for the primary and selected secondary efficacy measures in the modified intent-to-treat population. Clinical cure rates at day 9-12 were superior to placebo for the Astodrimer 3%, 1% and 0.5% Gel groups (62.5% [15/24; P = .002], 74.1% [20/27; P less then .001], and 55.2% [16/29; P = .001], respectively, vs. 22.2% [6/27]). At day 21-30, clinical cure rates were 46.2% (12/26) for the 1% dose vs. 11.5% for placebo (3/26; P = .006). A greater proportion of patients reported absence of vaginal discharge and vaginal odor at day 9-12 and day 21-30 for Astodrimer Gel groups compared with placebo. Adverse events considered potentially treatment-related occurred in only 25% of Astodrimer Gel-treated patients vs. 22% of placebo patients. CONCLUSION Astodrimer Gel once daily for 7 days was superior to placebo for treatment of bacterial vaginosis and was well-tolerated. The 1% dose consistently showed the strongest efficacy across endpoints. These results support a role for Astodrimer Gel, 1%, as an effective treatment for bacterial vaginosis.Biometric ratios of the relative length of the rays in the hand have been analyzed between primate species in the light of their hand function or phylogeny. However, how relative lengths among phalanges are mechanically linked to the grasping function of primates with different locomotor behaviors remains unclear. To clarify this, we calculated cross and triple-ratios, which are related to the torque distribution, and the torque generation mode at different joint angles using the lengths of the phalanges and metacarpal bones in 52 primates belonging to 25 species. The torque exerted on the finger joint and traction force of the flexor tendons necessary for a cylindrical grip and a suspensory hand posture were calculated using the moment arm of flexor tendons measured on magnetic resonance images, and were compared among Hylobates spp., Ateles sp., and Papio hamadryas. Finally, the torques calculated from the model were validated by a mechanical study detecting the force exerted on the phalanx by pulling the digital flexor muscles during suspension in these three species.
    The water-soluble fullerenols are novel carbon-based nanomaterials with unique properties, which afford them with wide agricultural applications. Iron (Fe) deficiency is the most common and widespread nutrition disorder affecting plants. Foliar Fe treatments of plants have been carried out with solutions devoid of fullerenol. In this study, the role of fullerenol [C60(OH)22-24] in alleviation of Fe deficiency in Cucumis sativus (a Strategy I plant) via foliar fertilization was investigated. Cucumber plants were grown hydroponically, either with (Fe) or in Fe-free (-Fe) nutrient solution. The following foliar spray treatments were applied fullerenol at final concentrations of 1 (F1) and 10 (F10) mg L-1; Fe(II)SO4·7H2O; Fe(II)-EDTA (ethylenediaminetetraacetic acid); and Fe(II)-F1 and Fe(II)-F10. https://www.selleckchem.com/ The best used compound was a combination of Fe(II)-sulfate with fullerenol, especially Fe-F1. The addition of fullerenol to Fe(II)-sulfate solutions significantly increased leaf-active Fe (extracted by an Fe(II) chelator) and re-greening at the site of application. The fullerenol-induced mutual influences did not appear when fullerenol was sprayed alone, suggesting a beneficial role of Fe(II)-fullerenol interactions in the penetration of Fe(II) in the leaves and re-greening under Fe-limited conditions. The results are of importance to enhancing the potential of foliar Fe fertilization as the commonly used strategy for ameliorating Fe deficiency and improving crop yield and quality.In coronary artery disease (CAD), exercise intolerance with reduced oxygen uptake at peak exercise (VO2peak) is assumed to primarily reflect cardiovascular limitation. However, oxygen transport and utilization depends on an integrated organ response, to which the normal pulmonary system may influence overall capacity. This study aimed to investigate the associations between normal values of lung function measures and VO2peak in patients with exercise intolerance and CAD. We hypothesized that forced expiratory lung volume in one second (FEV1), transfer factor of the lung for carbon monoxide (TLCO) and TLCO/alveolar volume (TLCO/VA) above lower limits of normal (LLN) are associated with VO2peak in these patients. We assessed patients with established CAD (n = 93; 21 women) referred for evaluation due to exercise intolerance from primary care to a private specialist clinic in Norway. Lung function tests and cardiopulmonary exercise testing (CPET) were performed. Z-scores of FEV1, FEV1/forced vital capacity (FVC), TLCO and TLCO/VA were calculated using the Global Lung Function Initiative (GLI) software and LLN was defined as the fifth percentile (z = -1.645). Non-obstructive patients, defined by both FEV1 and FEV1/FVC above LLN, were assessed. The associations of FEV1Z-score, TLCOZ-score and TLCO/VAZ-score above LLN with VO2peak were investigated using linear regression models. Mean VO2peak ± standard deviation (SD) was 23.8 ± 6.4 ml/kg/min in men and 19.7 ± 4.4 ml/kg/min in women. On average, one SD increase in FEV1, TLCO and TLCO/VA were associated with 1.4 (95% CI 0.2, 2.6), 2.6 (95% CI 1.2, 4.0) and 1.3 (95% CI 0.2, 2.5) ml/kg/min higher VO2peak, respectively. In non-obstructive patients with exercise intolerance and CAD, FEV1, TLCO and TLCO/VA above LLN are positively associated with VO2peak. This may imply a clinically significant influence of normal lung function on exercise capacity in these patients.BACKGROUND Astodrimer Gel contains a novel dendrimer intended to treat and prevent bacterial vaginosis. We assessed the efficacy and safety of Astodrimer Gel for treatment of bacterial vaginosis. METHODS 132 women with bacterial vaginosis were randomized 1111 to Astodrimer 0.5% (N = 34), 1% (N = 33), or 3% (N = 32) Gel or hydroxyethyl cellulose placebo gel (N = 33) at a dose of 5 g vaginally once daily for 7 days at 6 centers in the United States. The primary endpoint was clinical cure (no bacterial vaginosis vaginal discharge and no more than one of 1) vaginal pH ≥4.5; 2) ≥20% clue cells; or 3) positive whiff test) at study days 21-30. Secondary analyses included clinical cure at study days 9-12, patient-reported symptoms, acceptability and adverse events. RESULTS The Astodrimer 1% Gel dose was superior to placebo for the primary and selected secondary efficacy measures in the modified intent-to-treat population. Clinical cure rates at day 9-12 were superior to placebo for the Astodrimer 3%, 1% and 0.5% Gel groups (62.5% [15/24; P = .002], 74.1% [20/27; P less then .001], and 55.2% [16/29; P = .001], respectively, vs. 22.2% [6/27]). At day 21-30, clinical cure rates were 46.2% (12/26) for the 1% dose vs. 11.5% for placebo (3/26; P = .006). A greater proportion of patients reported absence of vaginal discharge and vaginal odor at day 9-12 and day 21-30 for Astodrimer Gel groups compared with placebo. Adverse events considered potentially treatment-related occurred in only 25% of Astodrimer Gel-treated patients vs. 22% of placebo patients. CONCLUSION Astodrimer Gel once daily for 7 days was superior to placebo for treatment of bacterial vaginosis and was well-tolerated. The 1% dose consistently showed the strongest efficacy across endpoints. These results support a role for Astodrimer Gel, 1%, as an effective treatment for bacterial vaginosis.Biometric ratios of the relative length of the rays in the hand have been analyzed between primate species in the light of their hand function or phylogeny. However, how relative lengths among phalanges are mechanically linked to the grasping function of primates with different locomotor behaviors remains unclear. To clarify this, we calculated cross and triple-ratios, which are related to the torque distribution, and the torque generation mode at different joint angles using the lengths of the phalanges and metacarpal bones in 52 primates belonging to 25 species. The torque exerted on the finger joint and traction force of the flexor tendons necessary for a cylindrical grip and a suspensory hand posture were calculated using the moment arm of flexor tendons measured on magnetic resonance images, and were compared among Hylobates spp., Ateles sp., and Papio hamadryas. Finally, the torques calculated from the model were validated by a mechanical study detecting the force exerted on the phalanx by pulling the digital flexor muscles during suspension in these three species.
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  • RESULTS The community recognized the presence of amphibians and reptiles that cohabit their space, as well as their potential habitats. Besides, the role of herpetofauna was recognized in the magical/religious traditions for some inhabitants of the region, mainly associated with the fate and cure of chronic diseases. In general, the perception of amphibians and reptiles varied according to the origin and gender of the people, which tend to have a more positive perception of reptiles than compared to amphibians in most cases. CONCLUSIONS Although there was a general lack of knowledge on the part of the inhabitants of the RFPCQ about the biological and ecological aspects of herpetofauna, the population recognized the basic information about the habitats of these animals within the reserve area. There is a wide variety of uses of amphibians and reptiles in traditional medicine. Greater efforts should be made in the transmission and dissemination of knowledge about the ecological functions of herpetofauna.Modern cardiopulmonary resuscitation (CPR) comprises an open airway, artificial ventilation, chest compressions and, if necessary, defibrillation. CPR has been intensively studied and tested to perfect an integrated and effective resuscitation system in the West. However, CPR efforts in China has been understudied and underreported. CPR has been performed for more than 2000 years in China. As early as the third century **, a Chinese doctor named Zhongjing Zhang presented a detailed program to save patients from suicide by hanging in the book entitled "Synopsis of the Golden Chamber". Dr. Zhang proposed "not only to save the body, but also to save the spirit", which remains a guiding principle in modern resuscitation to not only ensure cardiopulmonary recovery but also preserve the brain function. We aim to review and summarize efforts of CPR in China from a historic point of view.BACKGROUND There has been increased attention to the menstrual health management (MHM) needs of girls and young women in Eastern and Southern Africa, relating to dignity, and to the potential link between the lack of access to sanitary products and school absenteeism. In the South Africa, there is inadequate evidence to guide appropriate national responses. This study explored the extent of access to modern sanitary products amongst female high school learners and the range of needs and challenges that they face in managing their menses in school settings in Gauteng, South Africa. METHODS We collected mixed method data from 10 schools in Sedibeng district between June and August 2018. https://www.selleckchem.com/products/z-vad(oh)-fmk.html The qualitative component consisted of in-depth interviews with female learners (n = 30), educators (n = 8) and mothers of female learners (n = 9) and focus group discussions (FGDs) with male learners (n = 7) and female learners (n = 10). Five hundred and five female learners were recruited into the quantitative component consisroups in number of days missed. CONCLUSIONS Provision of sanitary products is important but only one component of a comprehensive MHM response. Ongoing attention over the link between product access and absenteeism risks overlooking complex systemic and structural factors which can negatively impact the sexual and reproductive health of learners in the school context, and more broadly.BACKGROUND Transbronchial needle aspiration (TBNA) is a minimally invasive procedure performed to diagnose lymph node (LN) adenopathy. TBNA with and without endobronchial ultrasound (EBUS) guidance has a high diagnostic yield for malignant LN enlargement, but the value for diagnosing benign LN enlargement has been less thoroughly investigated. METHODS We retrospectively evaluated 3540 patients with mediastinal LN enlargement who received TBNA. One hundred sixty-six patients with benign mediastinal lymphadenopathy were included and 293 LNs were biopsied. A positive result was defined as a specific histological abnormality. Conventional TBNA (cTBNA) and EBUS-TBNA, as well as cTBNA and transbronchial forceps biopsy (TBFB), were compared. The subgroup analysis was stratified by disease type and LN size. RESULTS A diagnosis was made in 76.84% of the EBUS-TBNA and 61.31% of the cTBNA (P  20 mm the difference was marginal. These findings were confirmed in a group of independent patients who received cTBNA plus EBUS-TBNA. The diagnostic yield did not differ between cTBNA and TBFB, but significantly increased to 76.67% when both modalities were employed. CONCLUSIONS EBUS-TBNA is the preferred minimally invasive diagnostic method for benign mediastinal LN disease. Combined cTBNA and TBFB is a safe and feasible alternative when EBUS is unavailable.BACKGROUND Alcohol consumption during pregnancy represents a significant public health concern. It has several adverse health effects for both the mother and the developing fetus. This study aimed to estimate the pooled prevalence and the effect size of associated factors of alcohol consumption during pregnancy in Sub-Saharan Africa countries. METHODS The results of the review were reported based on the Preferred Reporting Items for Systematic Review and Meta-Analysis statement (PRISMA) guideline and, it was registered in the Prospero database, number CRD42019127103. The available primary studies were collated from different databases PubMed, CINAHL, Cochrane Library, PsycINFO, Google Scholar, African Journals Online and Centre for Addiction and Mental Health Library. The main search terms were [((alcohol consumption) OR (alcohol drinking) OR (alcohol use) OR (ethanol use) OR (alcohol exposure)) AND ((pregnant women) OR (pregnant mother) OR (during pregnancy)) AND (Sub-Saharan Africa)]. We used the Joanna Brifrica. Alcohol consumption during pregnancy was associated with depression, partners' alcohol use, unplanned pregnancy and knowledge of the harmful effects of alcohol consumption. Therefore, this will be a basis for public policy and resource allocation for prevention initiatives.BACKGROUND Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is the most common periodic fever syndrome in children. There is considerable heterogeneity in management strategies and a lack of evidence-based treatment guidelines. Consensus treatment plans (CTPs) are standardized treatment regimens that are derived based upon best available evidence and current treatment practices that are a way to enable comparative effectiveness studies to identify optimal therapy and are less costly to execute than randomized, double blind placebo controlled trials. The purpose of this project was to develop CTPs and response criteria for PFAPA. METHODS The CARRA PFAPA Working Group is composed of pediatric rheumatologists, infectious disease specialists, allergists/immunologists and otolaryngologists. An extensive literature review was conducted followed by a survey to assess physician practice patterns. This was followed by virtual and in-person meetings between 2014 and 2018. Nominal group technique (NGT) was employed to develop CTPs, as well as inclusion criteria for entry into future treatment studies, and response criteria.
    RESULTS The community recognized the presence of amphibians and reptiles that cohabit their space, as well as their potential habitats. Besides, the role of herpetofauna was recognized in the magical/religious traditions for some inhabitants of the region, mainly associated with the fate and cure of chronic diseases. In general, the perception of amphibians and reptiles varied according to the origin and gender of the people, which tend to have a more positive perception of reptiles than compared to amphibians in most cases. CONCLUSIONS Although there was a general lack of knowledge on the part of the inhabitants of the RFPCQ about the biological and ecological aspects of herpetofauna, the population recognized the basic information about the habitats of these animals within the reserve area. There is a wide variety of uses of amphibians and reptiles in traditional medicine. Greater efforts should be made in the transmission and dissemination of knowledge about the ecological functions of herpetofauna.Modern cardiopulmonary resuscitation (CPR) comprises an open airway, artificial ventilation, chest compressions and, if necessary, defibrillation. CPR has been intensively studied and tested to perfect an integrated and effective resuscitation system in the West. However, CPR efforts in China has been understudied and underreported. CPR has been performed for more than 2000 years in China. As early as the third century BC, a Chinese doctor named Zhongjing Zhang presented a detailed program to save patients from suicide by hanging in the book entitled "Synopsis of the Golden Chamber". Dr. Zhang proposed "not only to save the body, but also to save the spirit", which remains a guiding principle in modern resuscitation to not only ensure cardiopulmonary recovery but also preserve the brain function. We aim to review and summarize efforts of CPR in China from a historic point of view.BACKGROUND There has been increased attention to the menstrual health management (MHM) needs of girls and young women in Eastern and Southern Africa, relating to dignity, and to the potential link between the lack of access to sanitary products and school absenteeism. In the South Africa, there is inadequate evidence to guide appropriate national responses. This study explored the extent of access to modern sanitary products amongst female high school learners and the range of needs and challenges that they face in managing their menses in school settings in Gauteng, South Africa. METHODS We collected mixed method data from 10 schools in Sedibeng district between June and August 2018. https://www.selleckchem.com/products/z-vad(oh)-fmk.html The qualitative component consisted of in-depth interviews with female learners (n = 30), educators (n = 8) and mothers of female learners (n = 9) and focus group discussions (FGDs) with male learners (n = 7) and female learners (n = 10). Five hundred and five female learners were recruited into the quantitative component consisroups in number of days missed. CONCLUSIONS Provision of sanitary products is important but only one component of a comprehensive MHM response. Ongoing attention over the link between product access and absenteeism risks overlooking complex systemic and structural factors which can negatively impact the sexual and reproductive health of learners in the school context, and more broadly.BACKGROUND Transbronchial needle aspiration (TBNA) is a minimally invasive procedure performed to diagnose lymph node (LN) adenopathy. TBNA with and without endobronchial ultrasound (EBUS) guidance has a high diagnostic yield for malignant LN enlargement, but the value for diagnosing benign LN enlargement has been less thoroughly investigated. METHODS We retrospectively evaluated 3540 patients with mediastinal LN enlargement who received TBNA. One hundred sixty-six patients with benign mediastinal lymphadenopathy were included and 293 LNs were biopsied. A positive result was defined as a specific histological abnormality. Conventional TBNA (cTBNA) and EBUS-TBNA, as well as cTBNA and transbronchial forceps biopsy (TBFB), were compared. The subgroup analysis was stratified by disease type and LN size. RESULTS A diagnosis was made in 76.84% of the EBUS-TBNA and 61.31% of the cTBNA (P  20 mm the difference was marginal. These findings were confirmed in a group of independent patients who received cTBNA plus EBUS-TBNA. The diagnostic yield did not differ between cTBNA and TBFB, but significantly increased to 76.67% when both modalities were employed. CONCLUSIONS EBUS-TBNA is the preferred minimally invasive diagnostic method for benign mediastinal LN disease. Combined cTBNA and TBFB is a safe and feasible alternative when EBUS is unavailable.BACKGROUND Alcohol consumption during pregnancy represents a significant public health concern. It has several adverse health effects for both the mother and the developing fetus. This study aimed to estimate the pooled prevalence and the effect size of associated factors of alcohol consumption during pregnancy in Sub-Saharan Africa countries. METHODS The results of the review were reported based on the Preferred Reporting Items for Systematic Review and Meta-Analysis statement (PRISMA) guideline and, it was registered in the Prospero database, number CRD42019127103. The available primary studies were collated from different databases PubMed, CINAHL, Cochrane Library, PsycINFO, Google Scholar, African Journals Online and Centre for Addiction and Mental Health Library. The main search terms were [((alcohol consumption) OR (alcohol drinking) OR (alcohol use) OR (ethanol use) OR (alcohol exposure)) AND ((pregnant women) OR (pregnant mother) OR (during pregnancy)) AND (Sub-Saharan Africa)]. We used the Joanna Brifrica. Alcohol consumption during pregnancy was associated with depression, partners' alcohol use, unplanned pregnancy and knowledge of the harmful effects of alcohol consumption. Therefore, this will be a basis for public policy and resource allocation for prevention initiatives.BACKGROUND Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is the most common periodic fever syndrome in children. There is considerable heterogeneity in management strategies and a lack of evidence-based treatment guidelines. Consensus treatment plans (CTPs) are standardized treatment regimens that are derived based upon best available evidence and current treatment practices that are a way to enable comparative effectiveness studies to identify optimal therapy and are less costly to execute than randomized, double blind placebo controlled trials. The purpose of this project was to develop CTPs and response criteria for PFAPA. METHODS The CARRA PFAPA Working Group is composed of pediatric rheumatologists, infectious disease specialists, allergists/immunologists and otolaryngologists. An extensive literature review was conducted followed by a survey to assess physician practice patterns. This was followed by virtual and in-person meetings between 2014 and 2018. Nominal group technique (NGT) was employed to develop CTPs, as well as inclusion criteria for entry into future treatment studies, and response criteria.
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  • Objectives This study aims to develop a new prognostic score based on changes in serial laboratory data from patients with pediatric acute liver failure (PALF). Methods We retrospectively reviewed data on 146 patients with PALF at the Seoul National University Children Hospital (SNUCH) and the Asan Medical Center (AMC). Daily morning laboratory records were obtained for up to 7 days after diagnosis of PALF total bilirubin (TB) (mg/dL), international normalized ratio for prothrombin time (INR) at enrolment; peak TB, peak INR, peak ammonia (μmol/L); the difference between the peak TB and TB at enrollment (ie, Δpeak TB), the difference between the peak INR and INR at enrollment (ie, Δpeak INR), the maximum change in serial TB (ie, Δdaily TB), the maximum change in serial INR level (ie, Δdaily INR). https://www.selleckchem.com/products/sf1670.html We assigned nontransplanted patients in SNUCH and AMC to derivation and validation cohorts, respectively. Results Δpeak TB, Δdaily TB, Δpeak INR, and Δdaily INR were significantly higher in the nonsurvival group. We developed a new score that can predict mortality in nontransplanted patients (derivation cohort n = 42, validation cohort n = 33). PALF-Delta score (PALF-Ds) = [0.232 × Δpeak TB (mg/dL)] + [2.263 × Δdaily INR] + [0.013 × peak ammonia (μmol/L)] - 4.498. The score yielded AUC 0.918 in the derivation cohort (sensitivity 81%, specificity 91%) and AUC 0.947 in the validation cohort (sensitivity 100%, specificity 89%). Conclusion A prognostic scoring system using the change of TB/INR may be useful for predicting mortality in patients with PALF.Objectives Infliximab (IFX), a monoclonal antibody directed against tumor necrosis factor alpha is a potent treatment option for inflammatory bowel disease (IBD). Dosing regimens in children are extrapolated from adult data using a fixed, weight-based dose, which is often not adequate. While clinical trials have focused on safety and efficacy, there is limited data on pharmacokinetic characteristics and immunogenicity of IFX in children. The objective was to provide a systematic overview of current literature on pharmacokinetic and immunogenicity of IFX in children with IBD, to assess the validity of current adult to pediatric dosing extrapolation. Methods A literature search identified publications up to October 2018. Eligibility criteria were study population consisting of children and/or adolescents with IBD, report of IFX trough levels and/or antibodies-to IFX, full text article or abstract, article in English, and original data. Results Initial electronic search yielded 2360 potentially relevant articles, with 1831 remaining after removal of duplicates. An additional search yielded another 202 potentially relevant articles. Of the 2033 retrieved articles, 2000 articles were excluded based on title, abstract, or eligibility criteria. Clearance of IFX was increased in young children and children with extensive disease, leading to lower trough levels after extrapolated dosing of 5 mg/kg, antibodies-to IFX emergence, and subsequent reduced efficacy. Conclusions Adult to pediatric weight-based dosing extrapolation is often inadequate. We provide several considerations for optimal dosing of IFX in children and adolescents with IBD.SARS-CoV-2, the novel coronavirus causing coronavirus disease 2019 (COVID-19), is now a global pandemic. Human-to-human transmission has been documented to occur through respiratory secretions, feces, aerosols, and contaminated environmental surfaces. Pediatric patients present a unique challenge as they may have minimal symptoms and yet transmit disease. Endoscopists face risk for infection with viruses like SARS-CoV-2, as the aerosol generating nature of endoscopy diffuses respiratory disease that can be spread via an airborne and droplet route. We describe our center's methodology for pediatric patient risk stratification to facilitate responsible use of endoscopic resources during this crisis. We also describe our recommendations for use of personal protective equipment by endoscopists, with the goal of ensuring the safety of ourselves, our anesthesiology and endoscopy staff, and our patients.The delivery of endoscopic care is changing rapidly in the era of Coronavirus Disease 2019 (COVID-19). The North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) Endoscopy and Procedures Committee has formulated this statement to offer practical guidance to help standardize endoscopy services for pediatric patients with the aim of minimizing COVID-19 transmission to staff, patients, and caregivers and to conserve personal protective equipment (PPE) during this critical time. Appropriate use of PPE is essential to minimize transmission and preserve supply. Pediatric endoscopic procedures are considered at high risk for COVID-19 transmission. We recommend that all pediatric endoscopic procedures are done in a negative pressure room with all staff using proper airborne, contact, and droplet precautions regardless of patient risk stratification. This includes appropriate use of a filtering face-piece respirator (N95, N99, FFP2/3, or PAPR), double gloves, facial protection (full visor and/or face shield), full body water-resistant disposable gown, shoe covers and a hairnet. In deciding which endoscopic procedures should proceed, it is important to weigh the risks and benefits to optimize healthcare delivery and minimize risk. To inform these decisions, we propose a framework for stratifying procedures as emergent (procedures that need to PROCEEED), urgent (PAUSE, weigh the benefits and risks in deciding whether to proceed) and elective (POSTPONE procedures). This statement was based on emerging evidence and is meant as a guide. It is important that all endoscopy facilities where pediatric procedures are performed follow current recommendations from public health agencies within their jurisdiction regarding infection prevention and control of COVID-19.Introduction With the current coronavirus disease 2019 (COVID-19) pandemic, concerns have been raised about the risk to children with inflammatory bowel diseases (IBD). We aimed to collate global experience and provide provisional guidance for managing paediatric IBD (PIBD) in the era of COVID-19. Methods An electronic reporting system of children with IBD infected with SARS-CoV-2 has been circulated among 102 PIBD centres affiliated with the Porto and Interest-group of ESPGHAN. A survey has been completed by major PIBD centres in China and South-Korea to explore management during the pandemic. A third survey collected current practice of PIBD treatment. Finally, guidance points for practice have been formulated and voted upon by 37 PIBD authors and Porto group members. Results Eight PIBD children had COVID-19 globally, all with mild infection without needing hospitalization despite treatment with immunomodulators and/or biologics. No cases have been reported in China and South Korea but biologic treatment has been delayed in 79 children, of whom 17 (22%) had exacerbation of their IBD.
    Objectives This study aims to develop a new prognostic score based on changes in serial laboratory data from patients with pediatric acute liver failure (PALF). Methods We retrospectively reviewed data on 146 patients with PALF at the Seoul National University Children Hospital (SNUCH) and the Asan Medical Center (AMC). Daily morning laboratory records were obtained for up to 7 days after diagnosis of PALF total bilirubin (TB) (mg/dL), international normalized ratio for prothrombin time (INR) at enrolment; peak TB, peak INR, peak ammonia (μmol/L); the difference between the peak TB and TB at enrollment (ie, Δpeak TB), the difference between the peak INR and INR at enrollment (ie, Δpeak INR), the maximum change in serial TB (ie, Δdaily TB), the maximum change in serial INR level (ie, Δdaily INR). https://www.selleckchem.com/products/sf1670.html We assigned nontransplanted patients in SNUCH and AMC to derivation and validation cohorts, respectively. Results Δpeak TB, Δdaily TB, Δpeak INR, and Δdaily INR were significantly higher in the nonsurvival group. We developed a new score that can predict mortality in nontransplanted patients (derivation cohort n = 42, validation cohort n = 33). PALF-Delta score (PALF-Ds) = [0.232 × Δpeak TB (mg/dL)] + [2.263 × Δdaily INR] + [0.013 × peak ammonia (μmol/L)] - 4.498. The score yielded AUC 0.918 in the derivation cohort (sensitivity 81%, specificity 91%) and AUC 0.947 in the validation cohort (sensitivity 100%, specificity 89%). Conclusion A prognostic scoring system using the change of TB/INR may be useful for predicting mortality in patients with PALF.Objectives Infliximab (IFX), a monoclonal antibody directed against tumor necrosis factor alpha is a potent treatment option for inflammatory bowel disease (IBD). Dosing regimens in children are extrapolated from adult data using a fixed, weight-based dose, which is often not adequate. While clinical trials have focused on safety and efficacy, there is limited data on pharmacokinetic characteristics and immunogenicity of IFX in children. The objective was to provide a systematic overview of current literature on pharmacokinetic and immunogenicity of IFX in children with IBD, to assess the validity of current adult to pediatric dosing extrapolation. Methods A literature search identified publications up to October 2018. Eligibility criteria were study population consisting of children and/or adolescents with IBD, report of IFX trough levels and/or antibodies-to IFX, full text article or abstract, article in English, and original data. Results Initial electronic search yielded 2360 potentially relevant articles, with 1831 remaining after removal of duplicates. An additional search yielded another 202 potentially relevant articles. Of the 2033 retrieved articles, 2000 articles were excluded based on title, abstract, or eligibility criteria. Clearance of IFX was increased in young children and children with extensive disease, leading to lower trough levels after extrapolated dosing of 5 mg/kg, antibodies-to IFX emergence, and subsequent reduced efficacy. Conclusions Adult to pediatric weight-based dosing extrapolation is often inadequate. We provide several considerations for optimal dosing of IFX in children and adolescents with IBD.SARS-CoV-2, the novel coronavirus causing coronavirus disease 2019 (COVID-19), is now a global pandemic. Human-to-human transmission has been documented to occur through respiratory secretions, feces, aerosols, and contaminated environmental surfaces. Pediatric patients present a unique challenge as they may have minimal symptoms and yet transmit disease. Endoscopists face risk for infection with viruses like SARS-CoV-2, as the aerosol generating nature of endoscopy diffuses respiratory disease that can be spread via an airborne and droplet route. We describe our center's methodology for pediatric patient risk stratification to facilitate responsible use of endoscopic resources during this crisis. We also describe our recommendations for use of personal protective equipment by endoscopists, with the goal of ensuring the safety of ourselves, our anesthesiology and endoscopy staff, and our patients.The delivery of endoscopic care is changing rapidly in the era of Coronavirus Disease 2019 (COVID-19). The North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) Endoscopy and Procedures Committee has formulated this statement to offer practical guidance to help standardize endoscopy services for pediatric patients with the aim of minimizing COVID-19 transmission to staff, patients, and caregivers and to conserve personal protective equipment (PPE) during this critical time. Appropriate use of PPE is essential to minimize transmission and preserve supply. Pediatric endoscopic procedures are considered at high risk for COVID-19 transmission. We recommend that all pediatric endoscopic procedures are done in a negative pressure room with all staff using proper airborne, contact, and droplet precautions regardless of patient risk stratification. This includes appropriate use of a filtering face-piece respirator (N95, N99, FFP2/3, or PAPR), double gloves, facial protection (full visor and/or face shield), full body water-resistant disposable gown, shoe covers and a hairnet. In deciding which endoscopic procedures should proceed, it is important to weigh the risks and benefits to optimize healthcare delivery and minimize risk. To inform these decisions, we propose a framework for stratifying procedures as emergent (procedures that need to PROCEEED), urgent (PAUSE, weigh the benefits and risks in deciding whether to proceed) and elective (POSTPONE procedures). This statement was based on emerging evidence and is meant as a guide. It is important that all endoscopy facilities where pediatric procedures are performed follow current recommendations from public health agencies within their jurisdiction regarding infection prevention and control of COVID-19.Introduction With the current coronavirus disease 2019 (COVID-19) pandemic, concerns have been raised about the risk to children with inflammatory bowel diseases (IBD). We aimed to collate global experience and provide provisional guidance for managing paediatric IBD (PIBD) in the era of COVID-19. Methods An electronic reporting system of children with IBD infected with SARS-CoV-2 has been circulated among 102 PIBD centres affiliated with the Porto and Interest-group of ESPGHAN. A survey has been completed by major PIBD centres in China and South-Korea to explore management during the pandemic. A third survey collected current practice of PIBD treatment. Finally, guidance points for practice have been formulated and voted upon by 37 PIBD authors and Porto group members. Results Eight PIBD children had COVID-19 globally, all with mild infection without needing hospitalization despite treatment with immunomodulators and/or biologics. No cases have been reported in China and South Korea but biologic treatment has been delayed in 79 children, of whom 17 (22%) had exacerbation of their IBD.
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  • Some types of spinal dysraphism can be accompanied by extraspinal cysts, including myelomeningocele, myelocystocele, myelocele, meningocele, limited dorsal myeloschisis, lipomyelomeningocele, and terminal myelocystocele. Each disease is classified according to the developmental mechanism, embryologic process, site of occurrence, or internal structure of the extraspinal cyst. In most cystic spinal dysraphisms except meningocele, part of the spinal cord is attached to the cyst dome. Most open spinal dysraphisms pose a risk of infection and require urgent surgical intervention, but when the cyst is accompanied by closed spinal dysraphism, the timing of surgery may vary. However, if the extraspinal cyst grows, it aggravates tethering by pulling the tip of the cord, which is attached to the dome of the cyst. This causes neurological deficits, so urgent surgery is required to release the tethered cord.Cases of syringomyelia associated with spinal dysraphism are distinct from those associated with hindbrain herniation or arachnoiditis in terms of the suspected pathogenetic mechanism. The symptoms of terminal syringomyelia are difficult to differentiate from the symptoms caused by spinal dysraphism. Nonetheless, syringomyelia has important clinical implications, as it is an important sign of cord tethering. The postoperative assessment of syringomyelia should be performed with caution.There has been confusion in the classification of terminal myelocystocele (TMCC) due to its diverse morphology and vague pathoembryogenesis. TMCC could be summarized as having the essential features of an elongated caudal spinal cord extruding out of the dorsal extraspinal space that fuses with the subcutaneous fat, which is in the shape of a trumpet-shaped cerebrospinal fluid-filled cyst. The extraspinal portion of the extruded spinal cord is nonfunctional. The morphological features suggest that TMCC is formed during secondary neurulation, specifically the failure of the degeneration of the secondary neural tube near the time of the terminal balloon. This review discusses the definition, as well as the clinical and surgical features, of TMCC with special emphasis on its pathoembryogenesis.Compared to any other decade, the last two decades have been the most dynamic period in terms of advances in the knowledge on spinal dysraphism. Among the several factors of rapid advancement, such as embryology during secondary neurulation and intraoperative neurophysiological monitoring, there is no doubt that Professor Dachling Pang stood high amidst the period. I review here the last two decades from my personal point of view on what has been achieved in the field of spinal dysraphism, focusing on occult tethered cord syndrome, lumbosacral lipomatous malformation, terminal myelocystocele, retained medullary cord, limited dorsal myeloschisis and junctional neural tube defect. There are still many issues to revise, add and extend. https://www.selleckchem.com/products/nocodazole.html Profound knowledge of basic science is critical, as well as refined clinical analysis. I expect that young scholars who follow the footsteps of precedent giants will shed bright light on this topic in the future.Retained medullary cord (RMC) is a relatively recent term. Pang et al. newly defined the RMC as a late arrest of secondary neurulation leaving a non-functional vestigial portion at the tip of the conus medullaris. RMC, which belongs to the category of closed spinal dysraphism, is a cord-like structure that is elongated from the conus toward the cul-de-sac. Because intraoperative electrophysiological confirmation of a non-functional conus is essential for the diagnosis of RMC, only a tentative or an assumptive diagnosis is possible before surgery or in cases of limited surgical exposure. We suggest the term 'possible RMC' for these cases. An RMC may cause tethered cord syndrome and thus requires surgery. This article reviews the literature to elucidate the pathoembryogenesis, clinical significance and treatment of RMCs.Background/Aims The prognosis of small cell lung cancer (SCLC) is still poor because of rapid recurrence, despite good response to initial chemotherapy. Additionally, patients' old ages and comorbidities are often obstacles that make it difficult to apply subsequent treatment after initial treatment. This retrospective study analyzed the correlation of post-progression survival (PPS) with overall survival (OS), and prognostic factors including comorbidities to figure out impact of subsequent chemotherapy on OS in elderly extensive disease SCLC. Methods We analyzed 101 patients of age 65 years or older who were recently diagnosed with extensive disease SCLC (ED-SCLC) in Korea University Medical Center between January 1995 and December 2015. The degree of comorbidity was scored using simplified comorbidity score (SCS). Correlation between PPS, progression-free survival (PFS) and OS was analyzed using a Pearson correlation coefficient. Cox proportional hazards regression was employed to examine the influence of clinical variables on survival. Results Median age of patients was 71 years old (range, 65 to 83). Median OS was 8.7 months (range, 0.3 to 42.7). PPS was a reliable factor on OS than PFS (R2 = 0.852, p 4 cycles of first line chemotherapy and subsequent second line chemotherapy. Conclusions PPS was more correlated with OS than PFS in elderly patients with ED-SCLC. The most important prognostic factors for PPS and OS included SCS and second line chemotherapy. Patients receiving subsequent treatment had increased OS regardless of degree of comorbidity.Background/Aims Lung function is an objective indicator of diagnosis and prognosis of respiratory diseases. Many common genetic variants have been associated with lung function in multiple ethnic populations. We looked for coding variants associated with forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC) in the Korean general population. Methods We carried out exome array analysis and lung function measurements of the FEV1 and FEV1/FVC in 7,524 individuals of the Korean population. We evaluated single variants with minor allele frequency greater than 0.5%. We performed look-ups for candidate coding variants associations in the UK Biobank, SpiroMeta, and CHARGE consortia. Results We identified coding variants in the SMIM29 (C6orf1) (p = 1.2 × 10-5) and HMGA1 locus on chromosome 6p21, the GIT2 (p = 6.5 × 10-5) locus on chromosome 12q24, and the ARHGEF40 (p = 9.9 × 10-5) locus on chromosome 14q11 as having a significant association with lung function (FEV1). We also confirmed a previously reported association with lung function and chronic obstructive pulmonary disease in the FAM13A (p = 4.
    Some types of spinal dysraphism can be accompanied by extraspinal cysts, including myelomeningocele, myelocystocele, myelocele, meningocele, limited dorsal myeloschisis, lipomyelomeningocele, and terminal myelocystocele. Each disease is classified according to the developmental mechanism, embryologic process, site of occurrence, or internal structure of the extraspinal cyst. In most cystic spinal dysraphisms except meningocele, part of the spinal cord is attached to the cyst dome. Most open spinal dysraphisms pose a risk of infection and require urgent surgical intervention, but when the cyst is accompanied by closed spinal dysraphism, the timing of surgery may vary. However, if the extraspinal cyst grows, it aggravates tethering by pulling the tip of the cord, which is attached to the dome of the cyst. This causes neurological deficits, so urgent surgery is required to release the tethered cord.Cases of syringomyelia associated with spinal dysraphism are distinct from those associated with hindbrain herniation or arachnoiditis in terms of the suspected pathogenetic mechanism. The symptoms of terminal syringomyelia are difficult to differentiate from the symptoms caused by spinal dysraphism. Nonetheless, syringomyelia has important clinical implications, as it is an important sign of cord tethering. The postoperative assessment of syringomyelia should be performed with caution.There has been confusion in the classification of terminal myelocystocele (TMCC) due to its diverse morphology and vague pathoembryogenesis. TMCC could be summarized as having the essential features of an elongated caudal spinal cord extruding out of the dorsal extraspinal space that fuses with the subcutaneous fat, which is in the shape of a trumpet-shaped cerebrospinal fluid-filled cyst. The extraspinal portion of the extruded spinal cord is nonfunctional. The morphological features suggest that TMCC is formed during secondary neurulation, specifically the failure of the degeneration of the secondary neural tube near the time of the terminal balloon. This review discusses the definition, as well as the clinical and surgical features, of TMCC with special emphasis on its pathoembryogenesis.Compared to any other decade, the last two decades have been the most dynamic period in terms of advances in the knowledge on spinal dysraphism. Among the several factors of rapid advancement, such as embryology during secondary neurulation and intraoperative neurophysiological monitoring, there is no doubt that Professor Dachling Pang stood high amidst the period. I review here the last two decades from my personal point of view on what has been achieved in the field of spinal dysraphism, focusing on occult tethered cord syndrome, lumbosacral lipomatous malformation, terminal myelocystocele, retained medullary cord, limited dorsal myeloschisis and junctional neural tube defect. There are still many issues to revise, add and extend. https://www.selleckchem.com/products/nocodazole.html Profound knowledge of basic science is critical, as well as refined clinical analysis. I expect that young scholars who follow the footsteps of precedent giants will shed bright light on this topic in the future.Retained medullary cord (RMC) is a relatively recent term. Pang et al. newly defined the RMC as a late arrest of secondary neurulation leaving a non-functional vestigial portion at the tip of the conus medullaris. RMC, which belongs to the category of closed spinal dysraphism, is a cord-like structure that is elongated from the conus toward the cul-de-sac. Because intraoperative electrophysiological confirmation of a non-functional conus is essential for the diagnosis of RMC, only a tentative or an assumptive diagnosis is possible before surgery or in cases of limited surgical exposure. We suggest the term 'possible RMC' for these cases. An RMC may cause tethered cord syndrome and thus requires surgery. This article reviews the literature to elucidate the pathoembryogenesis, clinical significance and treatment of RMCs.Background/Aims The prognosis of small cell lung cancer (SCLC) is still poor because of rapid recurrence, despite good response to initial chemotherapy. Additionally, patients' old ages and comorbidities are often obstacles that make it difficult to apply subsequent treatment after initial treatment. This retrospective study analyzed the correlation of post-progression survival (PPS) with overall survival (OS), and prognostic factors including comorbidities to figure out impact of subsequent chemotherapy on OS in elderly extensive disease SCLC. Methods We analyzed 101 patients of age 65 years or older who were recently diagnosed with extensive disease SCLC (ED-SCLC) in Korea University Medical Center between January 1995 and December 2015. The degree of comorbidity was scored using simplified comorbidity score (SCS). Correlation between PPS, progression-free survival (PFS) and OS was analyzed using a Pearson correlation coefficient. Cox proportional hazards regression was employed to examine the influence of clinical variables on survival. Results Median age of patients was 71 years old (range, 65 to 83). Median OS was 8.7 months (range, 0.3 to 42.7). PPS was a reliable factor on OS than PFS (R2 = 0.852, p 4 cycles of first line chemotherapy and subsequent second line chemotherapy. Conclusions PPS was more correlated with OS than PFS in elderly patients with ED-SCLC. The most important prognostic factors for PPS and OS included SCS and second line chemotherapy. Patients receiving subsequent treatment had increased OS regardless of degree of comorbidity.Background/Aims Lung function is an objective indicator of diagnosis and prognosis of respiratory diseases. Many common genetic variants have been associated with lung function in multiple ethnic populations. We looked for coding variants associated with forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC) in the Korean general population. Methods We carried out exome array analysis and lung function measurements of the FEV1 and FEV1/FVC in 7,524 individuals of the Korean population. We evaluated single variants with minor allele frequency greater than 0.5%. We performed look-ups for candidate coding variants associations in the UK Biobank, SpiroMeta, and CHARGE consortia. Results We identified coding variants in the SMIM29 (C6orf1) (p = 1.2 × 10-5) and HMGA1 locus on chromosome 6p21, the GIT2 (p = 6.5 × 10-5) locus on chromosome 12q24, and the ARHGEF40 (p = 9.9 × 10-5) locus on chromosome 14q11 as having a significant association with lung function (FEV1). We also confirmed a previously reported association with lung function and chronic obstructive pulmonary disease in the FAM13A (p = 4.
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  • The third study uses conventional simultaneous brightness contrast displays, but an unusual group of participants Congenitally blind children whom we were able to treat surgically. The results demonstrate an immediate susceptibility to the simultaneous brightness illusion after sight onset. Together, these data strongly constrain the search for mechanisms underlying a fundamental brightness phenomenon.A novel series of 4-substituted-3,4-dihydrobenzo[h]quinoline-2,5,6(1H)-triones as NQO1-directed antitumor agents were designed, synthesized, biologically evaluated. Compounds 3n, 3o and 3j proved to be good NQO1 substrates that showed increased metabolic rates relative to that of β-lapachone. In addition, 3n, 3o and 3j potently inhibited the growth of NQO1-rich breast cancer MCF-7 cell, liver hepatocellular HepG2 cell, and lung cancer A549 cell. In cellular mechanistic studies, the representative compound 3o triggered ROS generation depending on the NQO1 dose, and induce HepG2 cell apoptosis by the generated oxidative stress. In HepG2 xenografts mouse model, at the dose of 20 mg/kg, 3o remarkably suppressed the tumor growth without affecting the animal weights.It has been hypothesized that leptin level alterations in Eating Disorders (EDs) represent a maintaining factor for pathological reward-related ED behaviors, given leptin role in the dopaminergic reward systems. The aim of the present study was to evaluate the role of leptin in EDs as a mediator for the relationship between Body Mass Index (BMI) and several pathological behaviors, such as dietary restraint, compensatory exercise, vomiting, binge eating and emotional eating. Sixty-two patients with EDs and 41 healthy controls (HC) had their blood drawn and completed psychometric tests for the evaluation of general psychopathology, ED psychopathology and emotional eating. Moderated linear regression models showed that, in the presence of high levels of ED psychopathology, leptin levels were negatively associated with dietary restraint and compensatory exercise, and positively with emotional eating and binge eating. Finally, leptin showed an indirect effect on the association between BMI and all these reward-related behaviors. These results suggest that a variation of BMI maintains these pathological ED behaviors through a variation in leptin levels. Considering the role of leptin in reward circuits, the results seem to confirm an aberrant food-related reward mechanism in ED patients.Objectives Frailty is an increasingly common health condition and is seen more often due to the ageing population. This study reviews the evidence on the development and validation of these automated frailty measurement tools. Design Six databases PubMed, EMBASE, MEDLINE, CINAHL, Scopus, and Web of Science were electronically searched. Selected studies must have developed and validated a new frailty measurement tool using administrative health data and published results in a peer-reviewed, English-language journal. Selected studies were synthesized narratively. Setting and participants The review focused on large scale studies using administrative health data in developed countries. Participants included older people aged 65 years and above. Measures The main measures of review studies include discrimination power and the prediction ability of adverse health outcomes; performance against established frailty measures; and validation records. Results Five studies were selected for narrative synthesis after screening the full-text. https://www.selleckchem.com/products/fingolimod.html All frailty measurement tools in the selected five studies produced strong discrimination power with C-statistics ranging from 0.61-97. Two studies were independently validated in studies by other authors or conducted in other locations; one study developed an early prediction model, and no study has been applied in practice. Conclusions and implications Automated frailty measurement tools using administrative health data are still in the early development stage with five tools developed since 2016. Selected studies have strong prediction of adverse health outcomes. Future studies should include validation and refinement of these tools in other countries and assessment of their clinical utility and capacity to inform cost-effective policy and practice.Problem Several studies have indicated a protective effect of breastfeeding on reducing the risk of childhood obesity, however, this remains controversial. The aim of this meta-analysis is to clarify the association between breastfeeding and the risk of preschoolers' obesity. Eligibility criteria Prospective cohort studies published prior to December 1, 2019 were systematically searched in PubMed, EMBASE, the Web of Science and the Cochrane Library databases. Meta-analysis was performed using Stata 15.1. Sample Twenty-six publications involving 332,297 participants were eligible for inclusion. Results The pooled odds ratio (OR) of the risk of obesity in ever-breastfed preschoolers was 0.83 (95%CI [0.73,0.94]) compared with their never-breastfed counterparts. Random-effects dose-response model revealed a negative correlation between the duration of breastfeeding and risk of obesity (regression coefficient = -0.032, p = .001). Categorical analysis confirmed this dose-response association (1 day to less then 3 months of breastfeeding OR = 1.07, 95%CI [0.94,1.21]; 3 months to less then 6 months OR = 0.96, 95%CI [0.60,1.54]; ≥6 months OR = 0.67, 95%CI [0.58,0.77]). One month of breastfeeding was associated with a 4.0% decrease in risk of obesity (OR = 0.96/month of breastfeeding, 95% CI [0.95, 0.97]). Under the reference of never breastfeeding, the summary OR of exclusive breastfeeding was 0.53 (95%CI [0.45,0.63]). Conclusions Breastfeeding is inversely associated with a risk of early obesity in children aged two to six years. Moreover, there is a dose-response effect between duration of breastfeeding and reduced risk of early childhood obesity. Implications Clinical nurses' guidance and advice that prolong the duration of breastfeeding and promote exclusive breastfeeding are needed to prevent the development of later childhood obesity.
    The third study uses conventional simultaneous brightness contrast displays, but an unusual group of participants Congenitally blind children whom we were able to treat surgically. The results demonstrate an immediate susceptibility to the simultaneous brightness illusion after sight onset. Together, these data strongly constrain the search for mechanisms underlying a fundamental brightness phenomenon.A novel series of 4-substituted-3,4-dihydrobenzo[h]quinoline-2,5,6(1H)-triones as NQO1-directed antitumor agents were designed, synthesized, biologically evaluated. Compounds 3n, 3o and 3j proved to be good NQO1 substrates that showed increased metabolic rates relative to that of β-lapachone. In addition, 3n, 3o and 3j potently inhibited the growth of NQO1-rich breast cancer MCF-7 cell, liver hepatocellular HepG2 cell, and lung cancer A549 cell. In cellular mechanistic studies, the representative compound 3o triggered ROS generation depending on the NQO1 dose, and induce HepG2 cell apoptosis by the generated oxidative stress. In HepG2 xenografts mouse model, at the dose of 20 mg/kg, 3o remarkably suppressed the tumor growth without affecting the animal weights.It has been hypothesized that leptin level alterations in Eating Disorders (EDs) represent a maintaining factor for pathological reward-related ED behaviors, given leptin role in the dopaminergic reward systems. The aim of the present study was to evaluate the role of leptin in EDs as a mediator for the relationship between Body Mass Index (BMI) and several pathological behaviors, such as dietary restraint, compensatory exercise, vomiting, binge eating and emotional eating. Sixty-two patients with EDs and 41 healthy controls (HC) had their blood drawn and completed psychometric tests for the evaluation of general psychopathology, ED psychopathology and emotional eating. Moderated linear regression models showed that, in the presence of high levels of ED psychopathology, leptin levels were negatively associated with dietary restraint and compensatory exercise, and positively with emotional eating and binge eating. Finally, leptin showed an indirect effect on the association between BMI and all these reward-related behaviors. These results suggest that a variation of BMI maintains these pathological ED behaviors through a variation in leptin levels. Considering the role of leptin in reward circuits, the results seem to confirm an aberrant food-related reward mechanism in ED patients.Objectives Frailty is an increasingly common health condition and is seen more often due to the ageing population. This study reviews the evidence on the development and validation of these automated frailty measurement tools. Design Six databases PubMed, EMBASE, MEDLINE, CINAHL, Scopus, and Web of Science were electronically searched. Selected studies must have developed and validated a new frailty measurement tool using administrative health data and published results in a peer-reviewed, English-language journal. Selected studies were synthesized narratively. Setting and participants The review focused on large scale studies using administrative health data in developed countries. Participants included older people aged 65 years and above. Measures The main measures of review studies include discrimination power and the prediction ability of adverse health outcomes; performance against established frailty measures; and validation records. Results Five studies were selected for narrative synthesis after screening the full-text. https://www.selleckchem.com/products/fingolimod.html All frailty measurement tools in the selected five studies produced strong discrimination power with C-statistics ranging from 0.61-97. Two studies were independently validated in studies by other authors or conducted in other locations; one study developed an early prediction model, and no study has been applied in practice. Conclusions and implications Automated frailty measurement tools using administrative health data are still in the early development stage with five tools developed since 2016. Selected studies have strong prediction of adverse health outcomes. Future studies should include validation and refinement of these tools in other countries and assessment of their clinical utility and capacity to inform cost-effective policy and practice.Problem Several studies have indicated a protective effect of breastfeeding on reducing the risk of childhood obesity, however, this remains controversial. The aim of this meta-analysis is to clarify the association between breastfeeding and the risk of preschoolers' obesity. Eligibility criteria Prospective cohort studies published prior to December 1, 2019 were systematically searched in PubMed, EMBASE, the Web of Science and the Cochrane Library databases. Meta-analysis was performed using Stata 15.1. Sample Twenty-six publications involving 332,297 participants were eligible for inclusion. Results The pooled odds ratio (OR) of the risk of obesity in ever-breastfed preschoolers was 0.83 (95%CI [0.73,0.94]) compared with their never-breastfed counterparts. Random-effects dose-response model revealed a negative correlation between the duration of breastfeeding and risk of obesity (regression coefficient = -0.032, p = .001). Categorical analysis confirmed this dose-response association (1 day to less then 3 months of breastfeeding OR = 1.07, 95%CI [0.94,1.21]; 3 months to less then 6 months OR = 0.96, 95%CI [0.60,1.54]; ≥6 months OR = 0.67, 95%CI [0.58,0.77]). One month of breastfeeding was associated with a 4.0% decrease in risk of obesity (OR = 0.96/month of breastfeeding, 95% CI [0.95, 0.97]). Under the reference of never breastfeeding, the summary OR of exclusive breastfeeding was 0.53 (95%CI [0.45,0.63]). Conclusions Breastfeeding is inversely associated with a risk of early obesity in children aged two to six years. Moreover, there is a dose-response effect between duration of breastfeeding and reduced risk of early childhood obesity. Implications Clinical nurses' guidance and advice that prolong the duration of breastfeeding and promote exclusive breastfeeding are needed to prevent the development of later childhood obesity.
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  • 01% in the LCI + WLI group. This is a difference of 3.70% with a P value  less then  0.001 and an OR (95% CI) of 1.934 (1.362, 2.746). The lower limit of the 95% CI was greater than 0, and the superiority margin was 1%. CONCLUSION The detection rate of gastric neoplastic lesions was higher in the LCI + WLI group than in the WLI group, LCI might be an effective method for screening early gastric cancer.The questionable state of psychology as a science has been pointed out repeatedly over last hundred years. Sometimes programs to overcome the obvious limitations of psychology have been also proposed. So far, in vain. Zagaria with coauthors (this issue) bring the subject up again. They demonstrate that psychology today is characterized by the incoherence of definitions of core constructs and lack of consensus in the scientific community. The authors also suggest that psychology would do better by adopting a research program of a specific form of evolutionary psychology. In this paper I show, mostly on the basis of my earlier works on the same subject, that shortcomings of psychology today go **** deeper than the authors of the target article have discussed. Psychology today is characterized by fundamental epistemological and methodological problems. As the same shortcomings characterize the version of evolutionary psychology advocated by Zagaria and coauthors, it is not the best candidate to ground the future of psychology. I suggest the psychology misses unifying psychology of a specific kind, which basic principles were outlined by Vygotsky almost a century ago.BACKGROUND Recent improvement of machinery evaluation for the skin changes in various therapies enabled us to evaluate fine changes quantitatively. In this study, we performed evaluation of the changes in radiation dermatitis (RD) using quantitative and qualitative methods, and verified the validity of the conventional qualitative assessment for clinical use. METHODS Forty-three breast cancer patients received conventional fractionated radiotherapy to whole breast after breast-conserving surgery. Erythema, pigmentation and skin dryness were evaluated qualitatively, and biophysical parameters of RD were measured using a Multi-Display Device MDD4 with a Corneometer for capacitance, a Tewameter for transepidermal water loss (TEWL), a Mexameter for erythema index and melanin index. Measurements were performed periodically until 1 year. RESULTS The quantitative manifestations developed serially from skin erythema followed by dryness and pigmentation. Quantitative measurements detected the effects of irradiation earlier than that of qualitative indices. However, the grades of the domains in RD by qualitative and quantitative assessment showed similar time courses and peak periods. However, no significant correlation was observed between the skin dryness grade and skin barrier function. In contrast to serial increase in pigmentation grades, melanin index showed initial decrease followed by marked increase with significant correlation with pigmentation grades. CONCLUSION Subjectively and objectively measured results of RD were almost similar course and peak points through the study. Therefore, validity of the conventional qualitative scoring for RD is confirmed by the present quantitative assessments. Instrumental evaluations revealed the presence of modest inflammatory changes before radiotherapy and long-lasting skin dryness, suggesting indication of intervention for RD.Tripterygium hypoglaucum hutch (THH) is a plant of the genus tripterygium, which is also known as colquhounia, Gelsemiun elegan, and so on. It is mainly distributed in Yunnan, Guizhou, and Sichuan regions and other places in China. To study the immune mechanism of THH on related inflammatory cytokines in collagen II-induced arthritis (CIA) ****, healthy male C57BL/6 **** were used to model CIA ****. **** received THH 420 mg/kg/day or the same amount of normal saline (NS) by gavage for 20 days. https://www.selleckchem.com/products/SB-431542.html The thickness of the ankle joint in **** was observed, and the arthritis index was calculated. Related inflammatory cytokines were detected by real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. The results showed that after treatment with THH, the CIA **** had less swelling and destruction of the joints as well as decreased foot size and arthritis index. The mRNA and protein levels of TNF-α, IFN-γ, and IL-17A were lower in the THH-treated group than in the NS group (P  less then  0.05). In summary, THH has great significance in the treatment of CIA ****, including reduced related inflammatory cytokines expression level in both joint tissue and serum. The mechanism of THH in the treatment of CIA may be through the inhibition of the NF-kB-STAT3-IL-17 pathway, which also requires further experimental investigation.Many children growing up in cities are spending less time outdoors to escape the heat. This is contributing to childhood obesity and the prospect of a range of diseases in adulthood. When landscape architects and urban designers use a human thermal comfort model to test their designs for children's comfort, they would have to use a model essentially designed to simulate healthy adults. Yet there are many differences between the body of a child and an adult. The aim of this paper was to modify the thermal comfort model COMFA into a children's energy budget model through the consideration of the heat exchange of a child. The energy budget of a child can be up to 21 W/m2 higher than adults in hot summertime conditions, and 26 W/m2 lower in cold conditions. The model was validated through field studies of 65 children (32 boys and 33 girls) aged from 7-12 years old in 9 days from March to June in 2019, in 68 different microclimates ranging from cool to hot. A 5-point thermal comfort scale of energy budget for children was created using multinomial logistic regression, which revealed that children have a different range of thermal acceptability than adults. The frequency distribution of the actual thermal sensation and the predicted thermal comfort was improved using the new scale. The actual thermal sensation responses from children and the predicted thermal sensation using the model was determined to be positively significantly related. The accuracy of the model was 93.26%. This study has provided an effective children's energy budget model to predict children's thermal comfort. Its application can contribute to the design of thermally comfortable children's outdoor play areas by landscape architects and urban designers.
    01% in the LCI + WLI group. This is a difference of 3.70% with a P value  less then  0.001 and an OR (95% CI) of 1.934 (1.362, 2.746). The lower limit of the 95% CI was greater than 0, and the superiority margin was 1%. CONCLUSION The detection rate of gastric neoplastic lesions was higher in the LCI + WLI group than in the WLI group, LCI might be an effective method for screening early gastric cancer.The questionable state of psychology as a science has been pointed out repeatedly over last hundred years. Sometimes programs to overcome the obvious limitations of psychology have been also proposed. So far, in vain. Zagaria with coauthors (this issue) bring the subject up again. They demonstrate that psychology today is characterized by the incoherence of definitions of core constructs and lack of consensus in the scientific community. The authors also suggest that psychology would do better by adopting a research program of a specific form of evolutionary psychology. In this paper I show, mostly on the basis of my earlier works on the same subject, that shortcomings of psychology today go much deeper than the authors of the target article have discussed. Psychology today is characterized by fundamental epistemological and methodological problems. As the same shortcomings characterize the version of evolutionary psychology advocated by Zagaria and coauthors, it is not the best candidate to ground the future of psychology. I suggest the psychology misses unifying psychology of a specific kind, which basic principles were outlined by Vygotsky almost a century ago.BACKGROUND Recent improvement of machinery evaluation for the skin changes in various therapies enabled us to evaluate fine changes quantitatively. In this study, we performed evaluation of the changes in radiation dermatitis (RD) using quantitative and qualitative methods, and verified the validity of the conventional qualitative assessment for clinical use. METHODS Forty-three breast cancer patients received conventional fractionated radiotherapy to whole breast after breast-conserving surgery. Erythema, pigmentation and skin dryness were evaluated qualitatively, and biophysical parameters of RD were measured using a Multi-Display Device MDD4 with a Corneometer for capacitance, a Tewameter for transepidermal water loss (TEWL), a Mexameter for erythema index and melanin index. Measurements were performed periodically until 1 year. RESULTS The quantitative manifestations developed serially from skin erythema followed by dryness and pigmentation. Quantitative measurements detected the effects of irradiation earlier than that of qualitative indices. However, the grades of the domains in RD by qualitative and quantitative assessment showed similar time courses and peak periods. However, no significant correlation was observed between the skin dryness grade and skin barrier function. In contrast to serial increase in pigmentation grades, melanin index showed initial decrease followed by marked increase with significant correlation with pigmentation grades. CONCLUSION Subjectively and objectively measured results of RD were almost similar course and peak points through the study. Therefore, validity of the conventional qualitative scoring for RD is confirmed by the present quantitative assessments. Instrumental evaluations revealed the presence of modest inflammatory changes before radiotherapy and long-lasting skin dryness, suggesting indication of intervention for RD.Tripterygium hypoglaucum hutch (THH) is a plant of the genus tripterygium, which is also known as colquhounia, Gelsemiun elegan, and so on. It is mainly distributed in Yunnan, Guizhou, and Sichuan regions and other places in China. To study the immune mechanism of THH on related inflammatory cytokines in collagen II-induced arthritis (CIA) mice, healthy male C57BL/6 mice were used to model CIA mice. Mice received THH 420 mg/kg/day or the same amount of normal saline (NS) by gavage for 20 days. https://www.selleckchem.com/products/SB-431542.html The thickness of the ankle joint in mice was observed, and the arthritis index was calculated. Related inflammatory cytokines were detected by real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. The results showed that after treatment with THH, the CIA mice had less swelling and destruction of the joints as well as decreased foot size and arthritis index. The mRNA and protein levels of TNF-α, IFN-γ, and IL-17A were lower in the THH-treated group than in the NS group (P  less then  0.05). In summary, THH has great significance in the treatment of CIA mice, including reduced related inflammatory cytokines expression level in both joint tissue and serum. The mechanism of THH in the treatment of CIA may be through the inhibition of the NF-kB-STAT3-IL-17 pathway, which also requires further experimental investigation.Many children growing up in cities are spending less time outdoors to escape the heat. This is contributing to childhood obesity and the prospect of a range of diseases in adulthood. When landscape architects and urban designers use a human thermal comfort model to test their designs for children's comfort, they would have to use a model essentially designed to simulate healthy adults. Yet there are many differences between the body of a child and an adult. The aim of this paper was to modify the thermal comfort model COMFA into a children's energy budget model through the consideration of the heat exchange of a child. The energy budget of a child can be up to 21 W/m2 higher than adults in hot summertime conditions, and 26 W/m2 lower in cold conditions. The model was validated through field studies of 65 children (32 boys and 33 girls) aged from 7-12 years old in 9 days from March to June in 2019, in 68 different microclimates ranging from cool to hot. A 5-point thermal comfort scale of energy budget for children was created using multinomial logistic regression, which revealed that children have a different range of thermal acceptability than adults. The frequency distribution of the actual thermal sensation and the predicted thermal comfort was improved using the new scale. The actual thermal sensation responses from children and the predicted thermal sensation using the model was determined to be positively significantly related. The accuracy of the model was 93.26%. This study has provided an effective children's energy budget model to predict children's thermal comfort. Its application can contribute to the design of thermally comfortable children's outdoor play areas by landscape architects and urban designers.
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  • Background Constructing a medical image feature database according to the category of disease can achieve a quick retrieval of images with similar pathological features. Therefore, this approach has important application values in the fields such as auxiliary diagnosis, teaching, research, and telemedicine. Methods Based on the deep convolutional neural network, an image classifier applicable to brain disease was designed to distinguish between the image features of the different brain diseases with similar anatomical structures. Through the extraction and analysis of visual features, the images were labelled with the corresponding semantic features of a specific disease category, which can establish an association between the visual features of brain images and the semantic features of the category of disease which will permit to construct a disease category feature database of brain images. Results Based on the similarity measurement and the matching strategy of high-dimensional visual feature, a high-precision retrieval of brain image with semantics category was achieved, and the constructed disease category feature database of brain image was tested and evaluated through large numbers of pathological image retrieval experiments, the accuracy and the effectiveness of the proposed approach was verified. Conclusion The disease category feature database of brain image constructed by the proposed approach achieved a quick and effective retrieval of images with similar pathological features, which is beneficial to the categorization and analysis of intractable brain diseases. https://www.selleckchem.com/pharmacological_epigenetics.html This provides an effective application tool such as case-based image data management, evidence-based medicine and clinical decision support.This paper reports the results of an experiment involving text-messaging and emojis in laboratory trust games executed on mobile devices. Decomposing chat logs, I find that trust increases dramatically with the introduction of emojis to one-shot games, while reciprocation increases only modestly. Skin tones embedded in emojis impact sharing and resulting gains-to the benefit of some and detriment to others. Both light and dark skin players trust less on receipt of a dark skin tone emoji-suggestive of statistical discrimination. In this way, computer-mediated communication leads to reduced gains for dark-skinned persons. These results highlight the complex social judgment that motivates trust in an anonymous counterpart.Objective To evaluate the level of agreement between cardiologists regarding the management of oral anticoagulation (OAC) in patients with non-valvular atrial fibrillation (NVAF) in Spain. Materials and methods A two-round Delphi study was performed using an online survey. In round 1, panel members rated their level of agreement with the questionnaire items on a 9-point Likert scale. Item selection was based on acceptance by ≥66.6% of panellists and the agreement of the scientific committee. In round 2, the same panellists evaluated those items that did not meet consensus in round 1. Results A total of 238 experts participated in round 1; of these, 217 completed the round 2 survey. In round 1, 111 items from 4 dimensions (Thromboembolic and bleeding risk evaluation for treatment decision-making 18 items; Choice of OAC 39 items; OAC in specific cardiology situations 12 items; Patient participation and education 42 items) were evaluated. Consensus was reached for 92 items (83%). Over 80% of the experts agreed with the use of DOACs as the initial anticoagulant treatment when OAC is indicated. Panellists recommended the use of DOACs in patients at high risk of thromboembolic complications (CHA2DS2-VASc ≥3) (83%), haemorrhages (HAS-BLED ≥3) (89%) and poor quality of anticoagulation control (SAMe-TT2R2 >2) (76%), patients who fail to achieve an optimal therapeutic range after 3 months on VKA treatment (93%), and those who are to undergo cardioversion (80%). Panellists agreed that the efficacy and safety profile of each DOAC (98%), the availability of a specific reversal agent (72%) and patient's preference (85%) should be considered when prescribing a DOAC. A total of 97 items were ultimately accepted after round 2. Conclusions This Delphi panel study provides expert-based recommendations that may offer guidance on clinical decision-making for the management of OAC in NVAF. The importance of patient education and involvement has been highlighted.The nuclear lamina protein lamin A/C is a key component of the nuclear envelope. Mutations in the lamin A/C gene (LMNA) are identified in patients with various types of laminopathy-containing diseases, which have features of accelerated aging and osteoporosis. However, the underlying mechanisms for laminopathy-associated osteoporosis remain largely unclear. Here, we provide evidence that loss of lamin A/C in skeletal muscles, but not osteoblast (OB)-lineage cells, results in not only muscle aging-like deficit but also trabecular bone loss, a feature of osteoporosis. The latter is due in large part to elevated bone resorption. Further cellular studies show an increase of osteoclast (OC) differentiation in cocultures of bone marrow macrophages/monocytes (BMMs) and OBs after treatment with the conditioned medium (CM) from lamin A/C-deficient muscle cells. Antibody array screening analysis of the CM proteins identifies interleukin (IL)-6, whose expression is markedly increased in lamin A/C-deficient muscles. Inhibition of IL-6 by its blocking antibody in BMM-OB cocultures diminishes the increase of osteoclastogenesis. Knockout (KO) of IL-6 in muscle lamin A/C-KO **** diminishes the deficits in trabecular bone mass but not muscle. Further mechanistic studies reveal an elevation of cellular senescence marked by senescence-associated beta-galactosidase (SA-β-gal), p16Ink4a, and p53 in lamin A/C-deficient muscles and C2C12 muscle cells, and the p16Ink4a may induce senescence-associated secretory phenotype (SASP) and IL-6 expression. Taken together, these results suggest a critical role for skeletal muscle lamin A/C to prevent cellular senescence, IL-6 expression, hyperosteoclastogenesis, and trabecular bone loss, uncovering a pathological mechanism underlying the link between muscle aging/senescence and osteoporosis.
    Background Constructing a medical image feature database according to the category of disease can achieve a quick retrieval of images with similar pathological features. Therefore, this approach has important application values in the fields such as auxiliary diagnosis, teaching, research, and telemedicine. Methods Based on the deep convolutional neural network, an image classifier applicable to brain disease was designed to distinguish between the image features of the different brain diseases with similar anatomical structures. Through the extraction and analysis of visual features, the images were labelled with the corresponding semantic features of a specific disease category, which can establish an association between the visual features of brain images and the semantic features of the category of disease which will permit to construct a disease category feature database of brain images. Results Based on the similarity measurement and the matching strategy of high-dimensional visual feature, a high-precision retrieval of brain image with semantics category was achieved, and the constructed disease category feature database of brain image was tested and evaluated through large numbers of pathological image retrieval experiments, the accuracy and the effectiveness of the proposed approach was verified. Conclusion The disease category feature database of brain image constructed by the proposed approach achieved a quick and effective retrieval of images with similar pathological features, which is beneficial to the categorization and analysis of intractable brain diseases. https://www.selleckchem.com/pharmacological_epigenetics.html This provides an effective application tool such as case-based image data management, evidence-based medicine and clinical decision support.This paper reports the results of an experiment involving text-messaging and emojis in laboratory trust games executed on mobile devices. Decomposing chat logs, I find that trust increases dramatically with the introduction of emojis to one-shot games, while reciprocation increases only modestly. Skin tones embedded in emojis impact sharing and resulting gains-to the benefit of some and detriment to others. Both light and dark skin players trust less on receipt of a dark skin tone emoji-suggestive of statistical discrimination. In this way, computer-mediated communication leads to reduced gains for dark-skinned persons. These results highlight the complex social judgment that motivates trust in an anonymous counterpart.Objective To evaluate the level of agreement between cardiologists regarding the management of oral anticoagulation (OAC) in patients with non-valvular atrial fibrillation (NVAF) in Spain. Materials and methods A two-round Delphi study was performed using an online survey. In round 1, panel members rated their level of agreement with the questionnaire items on a 9-point Likert scale. Item selection was based on acceptance by ≥66.6% of panellists and the agreement of the scientific committee. In round 2, the same panellists evaluated those items that did not meet consensus in round 1. Results A total of 238 experts participated in round 1; of these, 217 completed the round 2 survey. In round 1, 111 items from 4 dimensions (Thromboembolic and bleeding risk evaluation for treatment decision-making 18 items; Choice of OAC 39 items; OAC in specific cardiology situations 12 items; Patient participation and education 42 items) were evaluated. Consensus was reached for 92 items (83%). Over 80% of the experts agreed with the use of DOACs as the initial anticoagulant treatment when OAC is indicated. Panellists recommended the use of DOACs in patients at high risk of thromboembolic complications (CHA2DS2-VASc ≥3) (83%), haemorrhages (HAS-BLED ≥3) (89%) and poor quality of anticoagulation control (SAMe-TT2R2 >2) (76%), patients who fail to achieve an optimal therapeutic range after 3 months on VKA treatment (93%), and those who are to undergo cardioversion (80%). Panellists agreed that the efficacy and safety profile of each DOAC (98%), the availability of a specific reversal agent (72%) and patient's preference (85%) should be considered when prescribing a DOAC. A total of 97 items were ultimately accepted after round 2. Conclusions This Delphi panel study provides expert-based recommendations that may offer guidance on clinical decision-making for the management of OAC in NVAF. The importance of patient education and involvement has been highlighted.The nuclear lamina protein lamin A/C is a key component of the nuclear envelope. Mutations in the lamin A/C gene (LMNA) are identified in patients with various types of laminopathy-containing diseases, which have features of accelerated aging and osteoporosis. However, the underlying mechanisms for laminopathy-associated osteoporosis remain largely unclear. Here, we provide evidence that loss of lamin A/C in skeletal muscles, but not osteoblast (OB)-lineage cells, results in not only muscle aging-like deficit but also trabecular bone loss, a feature of osteoporosis. The latter is due in large part to elevated bone resorption. Further cellular studies show an increase of osteoclast (OC) differentiation in cocultures of bone marrow macrophages/monocytes (BMMs) and OBs after treatment with the conditioned medium (CM) from lamin A/C-deficient muscle cells. Antibody array screening analysis of the CM proteins identifies interleukin (IL)-6, whose expression is markedly increased in lamin A/C-deficient muscles. Inhibition of IL-6 by its blocking antibody in BMM-OB cocultures diminishes the increase of osteoclastogenesis. Knockout (KO) of IL-6 in muscle lamin A/C-KO mice diminishes the deficits in trabecular bone mass but not muscle. Further mechanistic studies reveal an elevation of cellular senescence marked by senescence-associated beta-galactosidase (SA-β-gal), p16Ink4a, and p53 in lamin A/C-deficient muscles and C2C12 muscle cells, and the p16Ink4a may induce senescence-associated secretory phenotype (SASP) and IL-6 expression. Taken together, these results suggest a critical role for skeletal muscle lamin A/C to prevent cellular senescence, IL-6 expression, hyperosteoclastogenesis, and trabecular bone loss, uncovering a pathological mechanism underlying the link between muscle aging/senescence and osteoporosis.
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  • Here, we present a new series of hydrazide-bearing class I selective HDAC inhibitors designed based on panobinostat. The cap, linker, and zinc-binding group were derivatized to improve HDAC affinity and antileukemia efficacy. Lead inhibitor 13a shows picomolar or low nanomolar IC50 values against HDAC1 and HDAC3 and exhibits differential toxicity profiles toward multiple cancer cells with different FLT3 and p53 statuses. 13a indirectly inhibits the FLT3 signaling pathway and down-regulates master antiapoptotic proteins, resulting in the activation of pro-caspase3 in wt-p53 FLT3-ITD MV4-11 cells. While in the wt-FLT3 and p53-null cells, 13a is incapable of causing apoptosis at a therapeutic concentration. The MDM2 antagonist and the proteasome inhibitor promote 13a-triggered apoptosis by preventing p53 degradation. Furthermore, we demonstrate that apoptosis rather than autophagy is the key contributing factor for 13a-triggered cell death. When compared to panobinostat, 13a is not mutagenic and displays superior in vivo bioavailability and a higher AUC0-inf value.This work presents an improvement in the activity and catalytic lifetime of Pt deposits on Bi-modified Pt nanoparticles (Bi/Pt NP) toward formic acid oxidation (FAO). Using an irreversible adsorption method, Bi was deposited on Pt NP to form Bi/Pt NP and sequentially Pt was deposited on Bi/Pt NP to form Pt/Bi/Pt NP. Voltammetric studies of Pt NP, Bi/Pt NP, and Pt/Bi/Pt NPs supported that Pt deposits of Pt/Bi/Pt NPs provided quite a unique behavior simultaneous surface oxidation of deposited Pt and Bi and significant resistance to the oxidative removal of Bi. Furthermore, combined spectroscopic investigations revealed that the concentration of the employed Pt precursor ion solution determined the amount of deposited Pt from ∼0.2 to ∼0.4 in coverage. The best Pt/Bi/Pt NP catalyst with a Pt coverage of ∼0.25 enhanced the dehydrogenation processes below ∼0.4 V by a factor of more than 2 and increased the FAO current at ∼0.8 V roughly by 15 times, referring to those of Bi/Pt NP. The lifetime measurement works revealed that after the 1000th voltammetric cycle to 0.4 V, the FAO currents of Pt/Bi/Pt NPs were 2 and 4 times higher than those of Bi/Pt NP and Pt NP, respectively. The Pt deposits on Bi/Pt NP were concluded to play two roles in FAO the promotion of FAO processes to increase the activity and the retardation of Bi oxidative removal to maintain the activity **** longer.We investigated the potential for waterless urinal sealants fluids to remove pharmaceuticals from urine. 1H NMR, FTIR, and GC/MS characterization of the fluids indicated that they are mostly composed of aliphatic compounds. Removal of ethinyl estradiol was >40% for two of the three sealant fluids during simulated urination to a urinal cartridge but removal of seven other compounds with greater hydrophilicity was 3.5. At equilibrium with synthetic urine, removal ranged widely from 2% to 100%. Kow was poorly correlated with removal for both matrices at equilibrium, but Dow was correlated with removal from synthetic urine for two of the three sealants, indicating that ionization and hydrophilicity control partitioning between the urine and sealant phases. To improve removal during urination, where equilibrium is not achieved, we increased the hydraulic retention time 100-fold over that of typical male urination. https://www.selleckchem.com/products/z-lehd-fmk-s7313.html Removal of specific hydrophobic compounds increased, indicating that both hydrophobicity and kinetics control removal. Removal of ethinyl estradiol was ≥90% for all sealants in the increased hydraulic retention time experiment, demonstrating the potential for implementation to female urinals.In the present study, the memristive characteristics of hydrothermally grown TiO2 nanorod arrays, particularly, the difference in the retention time of the resistance state, are investigated in dependence of the array growth temperature. A volatile behavior is observed and related to a redistribution of oxygen vacancies over time. It is shown that the retention time increases for increasing array growth temperatures from several seconds up to 20 min. The relaxation behavior is also seen in the current-voltage characteristics, which do not show the common unipolar, bipolar, or complementary switching behavior. Instead, the temporal evolution depends on the duration of the applied voltage and on the nanowire growth temperature. Therefore, electronic measurements are combined with scanning electron and scanning transmission electron microscopy, so that the amount of oxygen defect-rich grain boundaries in the upper part of the nanowires can be linked to the differences in the current-voltage behavior and retention time.High-valent chiral oxidovanadium(V) complexes derived from 3,5-substituted-N-salicylidene-l-tert-leucine were used as catalysts in asymmetric reduction of N-benzyl-β-ketoamides. Among six different solvents, three different alcohol additives, and two different boranes examined, the use of pinacolborane in tetrahydrofuran (THF) with a t-BuOH additive led to the best results at -20 °C. The corresponding β-hydroxyamides can be furnished with yields up to 92% and an enantiomeric excess (ee) up to 99%. We have successfully extended this catalytic protocol for the synthesis of an (S)-duloxetine precursor.Single-molecule conductance of a B-N substituted phenanthrene derivative and its isoelectronic C═C counterpart was investigated by the scanning tunneling microscopy break junction (STM-BJ) technique. The incorporation of the B-N motif results in a better single-molecule conductivity than the C═C analogue. Furthermore, the Lewis acid-base reaction between F- and the B atom of the B-N motif leads to a decrease of the conductance of the BN derivative, which can be understood due to the shifting of the energy positions of the LUMO, as revealed by quantum transport calculations, even though the HOMO-LUMO gap decreases in the B-F Lewis acid-base. These findings provide insights for modulating electron transport properties by isoelectronic structure design. The B-N isoelectronic substituted structure could be a feasible way to design single-molecule devices such as switches and chemical sensors.
    Here, we present a new series of hydrazide-bearing class I selective HDAC inhibitors designed based on panobinostat. The cap, linker, and zinc-binding group were derivatized to improve HDAC affinity and antileukemia efficacy. Lead inhibitor 13a shows picomolar or low nanomolar IC50 values against HDAC1 and HDAC3 and exhibits differential toxicity profiles toward multiple cancer cells with different FLT3 and p53 statuses. 13a indirectly inhibits the FLT3 signaling pathway and down-regulates master antiapoptotic proteins, resulting in the activation of pro-caspase3 in wt-p53 FLT3-ITD MV4-11 cells. While in the wt-FLT3 and p53-null cells, 13a is incapable of causing apoptosis at a therapeutic concentration. The MDM2 antagonist and the proteasome inhibitor promote 13a-triggered apoptosis by preventing p53 degradation. Furthermore, we demonstrate that apoptosis rather than autophagy is the key contributing factor for 13a-triggered cell death. When compared to panobinostat, 13a is not mutagenic and displays superior in vivo bioavailability and a higher AUC0-inf value.This work presents an improvement in the activity and catalytic lifetime of Pt deposits on Bi-modified Pt nanoparticles (Bi/Pt NP) toward formic acid oxidation (FAO). Using an irreversible adsorption method, Bi was deposited on Pt NP to form Bi/Pt NP and sequentially Pt was deposited on Bi/Pt NP to form Pt/Bi/Pt NP. Voltammetric studies of Pt NP, Bi/Pt NP, and Pt/Bi/Pt NPs supported that Pt deposits of Pt/Bi/Pt NPs provided quite a unique behavior simultaneous surface oxidation of deposited Pt and Bi and significant resistance to the oxidative removal of Bi. Furthermore, combined spectroscopic investigations revealed that the concentration of the employed Pt precursor ion solution determined the amount of deposited Pt from ∼0.2 to ∼0.4 in coverage. The best Pt/Bi/Pt NP catalyst with a Pt coverage of ∼0.25 enhanced the dehydrogenation processes below ∼0.4 V by a factor of more than 2 and increased the FAO current at ∼0.8 V roughly by 15 times, referring to those of Bi/Pt NP. The lifetime measurement works revealed that after the 1000th voltammetric cycle to 0.4 V, the FAO currents of Pt/Bi/Pt NPs were 2 and 4 times higher than those of Bi/Pt NP and Pt NP, respectively. The Pt deposits on Bi/Pt NP were concluded to play two roles in FAO the promotion of FAO processes to increase the activity and the retardation of Bi oxidative removal to maintain the activity much longer.We investigated the potential for waterless urinal sealants fluids to remove pharmaceuticals from urine. 1H NMR, FTIR, and GC/MS characterization of the fluids indicated that they are mostly composed of aliphatic compounds. Removal of ethinyl estradiol was >40% for two of the three sealant fluids during simulated urination to a urinal cartridge but removal of seven other compounds with greater hydrophilicity was 3.5. At equilibrium with synthetic urine, removal ranged widely from 2% to 100%. Kow was poorly correlated with removal for both matrices at equilibrium, but Dow was correlated with removal from synthetic urine for two of the three sealants, indicating that ionization and hydrophilicity control partitioning between the urine and sealant phases. To improve removal during urination, where equilibrium is not achieved, we increased the hydraulic retention time 100-fold over that of typical male urination. https://www.selleckchem.com/products/z-lehd-fmk-s7313.html Removal of specific hydrophobic compounds increased, indicating that both hydrophobicity and kinetics control removal. Removal of ethinyl estradiol was ≥90% for all sealants in the increased hydraulic retention time experiment, demonstrating the potential for implementation to female urinals.In the present study, the memristive characteristics of hydrothermally grown TiO2 nanorod arrays, particularly, the difference in the retention time of the resistance state, are investigated in dependence of the array growth temperature. A volatile behavior is observed and related to a redistribution of oxygen vacancies over time. It is shown that the retention time increases for increasing array growth temperatures from several seconds up to 20 min. The relaxation behavior is also seen in the current-voltage characteristics, which do not show the common unipolar, bipolar, or complementary switching behavior. Instead, the temporal evolution depends on the duration of the applied voltage and on the nanowire growth temperature. Therefore, electronic measurements are combined with scanning electron and scanning transmission electron microscopy, so that the amount of oxygen defect-rich grain boundaries in the upper part of the nanowires can be linked to the differences in the current-voltage behavior and retention time.High-valent chiral oxidovanadium(V) complexes derived from 3,5-substituted-N-salicylidene-l-tert-leucine were used as catalysts in asymmetric reduction of N-benzyl-β-ketoamides. Among six different solvents, three different alcohol additives, and two different boranes examined, the use of pinacolborane in tetrahydrofuran (THF) with a t-BuOH additive led to the best results at -20 °C. The corresponding β-hydroxyamides can be furnished with yields up to 92% and an enantiomeric excess (ee) up to 99%. We have successfully extended this catalytic protocol for the synthesis of an (S)-duloxetine precursor.Single-molecule conductance of a B-N substituted phenanthrene derivative and its isoelectronic C═C counterpart was investigated by the scanning tunneling microscopy break junction (STM-BJ) technique. The incorporation of the B-N motif results in a better single-molecule conductivity than the C═C analogue. Furthermore, the Lewis acid-base reaction between F- and the B atom of the B-N motif leads to a decrease of the conductance of the BN derivative, which can be understood due to the shifting of the energy positions of the LUMO, as revealed by quantum transport calculations, even though the HOMO-LUMO gap decreases in the B-F Lewis acid-base. These findings provide insights for modulating electron transport properties by isoelectronic structure design. The B-N isoelectronic substituted structure could be a feasible way to design single-molecule devices such as switches and chemical sensors.
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  • 85 for association of DKK3 concentrations with chronic GVHD. Multiple linear regression analysis showed that chronic GVHD with or without steroid treatment and patient age were independently associated with DKK3 concentrations. Patients with high DKK3 concentrations had a higher nonrelapse mortality than those with low concentrations. The lower IL1RAP concentrations in patients with sclerotic GVHD compared with other conditions in the discovery cohort were not confirmed in the verification cohort. DKK3 is a novel biomarker for chronic GVHD. Further studies are needed to determine the biological functions of DKK3 in the pathogenesis of chronic GVHD.Caloric starvation, as well as various diets, has been proposed to increase the oxidative DNA damage induced by radiotherapy (RT). However, some diets could have dual effects, sometimes promoting cancer growth, whereas proposing caloric restriction may appear counterproductive during RT considering that the maintenance of weight is a major factor for the success of this therapy. A systematic review was performed via a PubMed search on RT and fasting, or caloric restriction, ketogenic diet (>75% of fat-derived energy intake), protein starvation, amino acid restriction, as well as the Warburg effect. Twenty-six eligible original articles (17 preclinical studies and 9 clinical noncontrolled studies on low-carbohydrate, high-fat diets popularized as ketogenic diets, representing a total of 77 patients) were included. Preclinical experiments suggest that a short period of fasting prior to radiation, and/or transient caloric restriction during treatment course, can increase tumor responsiveness. These regimens promdeserve to be tested to improve efficiency of radiation.Context It is unclear whether vitamin D supplementation reduces risk of falls, and results from randomized controlled trials (RCTs) are conflicting. Objective To determine whether 2000 IU/day of supplemental vitamin D3 decreases fall risk. Design VITamin D and OmegA-3 TriaL (VITAL) is a double-blind, placebo-controlled RCT including 25,871 adults, randomized November 2011-March 2014 and treated for 5.3 years (median). Setting Nationwide study. Participants Men ≥50 and women ≥55 years (mean age 67.1 years) without cancer or cardiovascular disease at baseline. Interventions Vitamin D3 (cholecalciferol; 2,000 IU/day) and/or omega-3 fatty acids (1 g/day) or respective placebos in a 2X2 factorial design. https://www.selleckchem.com/products/z-vad(oh)-fmk.html Main outcome measures Two or more falls, falls resulting in a doctor or hospital visit. Results Baseline serum total 25-hydroxyvitamin D [25(OH)D] level was 77 nmol/L; characteristics were well-balanced between groups. Numbers of participants with ≥2 falls were similar between active and placebo groups (9.8% vs. 9.4%). Over 5 years, there were no differences in the proportion having ≥2 falls (OR=0.97; 95% CI, 0.90-1.05, p=0.50), falls resulting in a doctor visit (OR=1.03; 95% CI, 0.94-1.13, p=0.46) or resulting in a hospital visit (OR=1.04; 95% CI, 0.90-1.19, p=0.61) between groups. Results did not differ between those with baseline 25(OH)D 50 nmol/L or other cutpoints. Conclusion Daily supplemental vitamin D3 vs. placebo did not decrease fall risk in generally healthy adults not selected for vitamin D insufficiency. This large RCT does not indicate that supplemental vitamin D should be used for primary prevention of falls in the U.S. population.Human catechol-O-methyltransferase (COMT), a key enzyme related to neurotransmitter metabolism, catalyzes a methyl transfer from S-adenosylmethionine (SAM) to catechol. Although extensive studies aim to understand the enzyme mechanisms, the connection of protein dynamics and enzyme catalysis is still not clear. Here, W38in (Trp143Phe) and W38in/Y68A (Trp143Phe with Tyr68Ala) mutants were carried out to study the relationship of dynamics and catalysis in nanosecond time scale using time-resolved fluorescence lifetimes and Stokes shifts in various solvents. The comprehensive data implied the mutant W38in/Y68A with lower activity is more rigid than the "WT"-W38in, suggesting the importance of flexibility at residue 38 to maintain the optimal catalysis.Background Poor lifestyles have been linked to insulin insensitivity/hyperinsulinemia, which may contribute to downstream changes such as inflammation and oxidative damage and the development of chronic diseases. As a biomarker of intracellular oxidative stress, leukocyte mitochondrial DNA copy number (mtDNA-CN) has been related to lifestyle factors including diet and weight. No epidemiologic study has examined the relation between combined insulinemic potential of lifestyle and mtDNA-CN. Objectives Our aim was to examine the association between Empirical Lifestyle Index for Hyperinsulinemia (ELIH) and leukocyte mtDNA-CN in US men and women. Methods This cross-sectional analysis included 2835 white adults without cancers, diabetes, or cardiovascular disease at blood collection, including 2160 women from the Nurses' Health Study and 675 men from the Health Professionals Follow-Up Study. ELIH is an index based on plasma C-peptide that characterizes the insulinemic potential of lifestyle (diet, body weight, and physical activity). Relative mtDNA-CN in peripheral blood leukocytes was measured by qPCR-based assay. Results We found a significant inverse association between ELIH and mtDNA-CN. In multivariable-adjusted linear models, absolute least squares means ± SDs of mtDNA-CN z score across ELIH quintiles in women were as follows Q1 0.14 ± 0.05; Q2 0.04 ± 0.06; Q3 0.008 ± 0.05; Q4 0.01 ± 0.05; and Q5 -0.06 ± 0.05 (P-trend = 0.006). Means ± SDs in men were as follows Q1 0.25 ± 0.09; Q2 0.23 ± 0.09; Q3 0.07 ± 0.09; Q4 0.02 ± 0.09; and Q5 -0.04 ± 0.09 (P-trend = 0.007). Means ± SDs in all participants were as follows Q1 0.16 ± 0.05; Q2 0.07 ± 0.05; Q3 0.01 ± 0.05; Q4 0.01 ± 0.05; and Q5 -0.05 ± 0.05 (P-trend = 0.0004). Conclusions Hyperinsulinemic lifestyles (i.e., higher ELIH) were associated with lower leukocyte mtDNA-CN among subjects without major diseases, suggesting that the difference in lifestyle insulinemic potential may be related to excessive oxidative stress damage.
    85 for association of DKK3 concentrations with chronic GVHD. Multiple linear regression analysis showed that chronic GVHD with or without steroid treatment and patient age were independently associated with DKK3 concentrations. Patients with high DKK3 concentrations had a higher nonrelapse mortality than those with low concentrations. The lower IL1RAP concentrations in patients with sclerotic GVHD compared with other conditions in the discovery cohort were not confirmed in the verification cohort. DKK3 is a novel biomarker for chronic GVHD. Further studies are needed to determine the biological functions of DKK3 in the pathogenesis of chronic GVHD.Caloric starvation, as well as various diets, has been proposed to increase the oxidative DNA damage induced by radiotherapy (RT). However, some diets could have dual effects, sometimes promoting cancer growth, whereas proposing caloric restriction may appear counterproductive during RT considering that the maintenance of weight is a major factor for the success of this therapy. A systematic review was performed via a PubMed search on RT and fasting, or caloric restriction, ketogenic diet (>75% of fat-derived energy intake), protein starvation, amino acid restriction, as well as the Warburg effect. Twenty-six eligible original articles (17 preclinical studies and 9 clinical noncontrolled studies on low-carbohydrate, high-fat diets popularized as ketogenic diets, representing a total of 77 patients) were included. Preclinical experiments suggest that a short period of fasting prior to radiation, and/or transient caloric restriction during treatment course, can increase tumor responsiveness. These regimens promdeserve to be tested to improve efficiency of radiation.Context It is unclear whether vitamin D supplementation reduces risk of falls, and results from randomized controlled trials (RCTs) are conflicting. Objective To determine whether 2000 IU/day of supplemental vitamin D3 decreases fall risk. Design VITamin D and OmegA-3 TriaL (VITAL) is a double-blind, placebo-controlled RCT including 25,871 adults, randomized November 2011-March 2014 and treated for 5.3 years (median). Setting Nationwide study. Participants Men ≥50 and women ≥55 years (mean age 67.1 years) without cancer or cardiovascular disease at baseline. Interventions Vitamin D3 (cholecalciferol; 2,000 IU/day) and/or omega-3 fatty acids (1 g/day) or respective placebos in a 2X2 factorial design. https://www.selleckchem.com/products/z-vad(oh)-fmk.html Main outcome measures Two or more falls, falls resulting in a doctor or hospital visit. Results Baseline serum total 25-hydroxyvitamin D [25(OH)D] level was 77 nmol/L; characteristics were well-balanced between groups. Numbers of participants with ≥2 falls were similar between active and placebo groups (9.8% vs. 9.4%). Over 5 years, there were no differences in the proportion having ≥2 falls (OR=0.97; 95% CI, 0.90-1.05, p=0.50), falls resulting in a doctor visit (OR=1.03; 95% CI, 0.94-1.13, p=0.46) or resulting in a hospital visit (OR=1.04; 95% CI, 0.90-1.19, p=0.61) between groups. Results did not differ between those with baseline 25(OH)D 50 nmol/L or other cutpoints. Conclusion Daily supplemental vitamin D3 vs. placebo did not decrease fall risk in generally healthy adults not selected for vitamin D insufficiency. This large RCT does not indicate that supplemental vitamin D should be used for primary prevention of falls in the U.S. population.Human catechol-O-methyltransferase (COMT), a key enzyme related to neurotransmitter metabolism, catalyzes a methyl transfer from S-adenosylmethionine (SAM) to catechol. Although extensive studies aim to understand the enzyme mechanisms, the connection of protein dynamics and enzyme catalysis is still not clear. Here, W38in (Trp143Phe) and W38in/Y68A (Trp143Phe with Tyr68Ala) mutants were carried out to study the relationship of dynamics and catalysis in nanosecond time scale using time-resolved fluorescence lifetimes and Stokes shifts in various solvents. The comprehensive data implied the mutant W38in/Y68A with lower activity is more rigid than the "WT"-W38in, suggesting the importance of flexibility at residue 38 to maintain the optimal catalysis.Background Poor lifestyles have been linked to insulin insensitivity/hyperinsulinemia, which may contribute to downstream changes such as inflammation and oxidative damage and the development of chronic diseases. As a biomarker of intracellular oxidative stress, leukocyte mitochondrial DNA copy number (mtDNA-CN) has been related to lifestyle factors including diet and weight. No epidemiologic study has examined the relation between combined insulinemic potential of lifestyle and mtDNA-CN. Objectives Our aim was to examine the association between Empirical Lifestyle Index for Hyperinsulinemia (ELIH) and leukocyte mtDNA-CN in US men and women. Methods This cross-sectional analysis included 2835 white adults without cancers, diabetes, or cardiovascular disease at blood collection, including 2160 women from the Nurses' Health Study and 675 men from the Health Professionals Follow-Up Study. ELIH is an index based on plasma C-peptide that characterizes the insulinemic potential of lifestyle (diet, body weight, and physical activity). Relative mtDNA-CN in peripheral blood leukocytes was measured by qPCR-based assay. Results We found a significant inverse association between ELIH and mtDNA-CN. In multivariable-adjusted linear models, absolute least squares means ± SDs of mtDNA-CN z score across ELIH quintiles in women were as follows Q1 0.14 ± 0.05; Q2 0.04 ± 0.06; Q3 0.008 ± 0.05; Q4 0.01 ± 0.05; and Q5 -0.06 ± 0.05 (P-trend = 0.006). Means ± SDs in men were as follows Q1 0.25 ± 0.09; Q2 0.23 ± 0.09; Q3 0.07 ± 0.09; Q4 0.02 ± 0.09; and Q5 -0.04 ± 0.09 (P-trend = 0.007). Means ± SDs in all participants were as follows Q1 0.16 ± 0.05; Q2 0.07 ± 0.05; Q3 0.01 ± 0.05; Q4 0.01 ± 0.05; and Q5 -0.05 ± 0.05 (P-trend = 0.0004). Conclusions Hyperinsulinemic lifestyles (i.e., higher ELIH) were associated with lower leukocyte mtDNA-CN among subjects without major diseases, suggesting that the difference in lifestyle insulinemic potential may be related to excessive oxidative stress damage.
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  • The use of "omics" is increasing in research areas looking to identify biomarkers or early preclinical signs of disease or to increase understanding of complex pathological processes that determines prognosis of the disease. Diabetic kidney disease is no exception as it is an area in need of further improvement of both understanding and prognosis. In addition, there is a notion that pretreatment investigations using techniques like proteomics, lipidomics and metabolomics can help individualize therapy thus fulfilling the wish for personalized medicine. An increasing number of cohort studies using these techniques are published, but only few have been validated in external cohorts or even replicated by other groups. In essence, to achieve clinical impact and usefulness, prospective validation is needed. So far, only the urinary proteomics based PRIORITY study has tried to do this, as discussed in this review. Other areas are promising, but are currently lacking such efforts. In this review we report and discuss the current status of urinary proteomics as well as plasma metabolomics and lipidomics with an overview of the results so far, and with some comments and perspectives regarding future developments and implementation. As is evident, these techniques are promising, but there is still some way before widespread clinical use can be foreseen.We investigated the potential role of miR-490-3p in ischemia reperfusion (IR) injury. We first determined the expression of miR-490-3p and autophagy-related 4B cysteine (ATG4B) in IR. Then, to explore whether miR-490-3p would affect autophagy, apoptosis, and IR injury, we evaluated apoptosis, autophagy, and infarct size via gain- and loss-of-function experiments. Furthermore, we used adenovirus to enhance or inhibit the expression of ATG4B, and then measured autophagy, apoptosis, and IR injury. miR-490-3p was downregulated in the hearts during the process of IR, while ATG4B was upregulated. The inhibition of miR-490-3p or overexpression of ATG4B could promote the expression of LC3II, increase the autolysosomes, inhibit the expression of p62, and reduce infarct size. On all accounts, the inhibition of miR-490-3p could promote autophagy to reduce myocardial IR injury by upregulating ATG4B, a finding that provides new insights for the protective mechanism of autophagy in IR. Graphical Abstract.A two-dimensional model is developed to simulate dendrite growth and movement in a gravity environment. The model combines the features of cellular automaton and lattice Boltzmann methods. Two sets of distribution functions are adopted to calculate the melt flow and solute transport simultaneously. The fluid force acting on the dendrite is calculated by extending the basic flow simulation at the solid-liquid interface. Incorporating the force interaction between melt flow and solidified dendrite into the algorithm for dendritic growth, the movement of a growing dendrite in the flowing melt can be simulated. After model validation, the coupled model has been applied to simulate the evolution and motion of an individual nucleus that grows into a dendrite in the presence of gravitational force. It is found that the dendrite growth is strongly influenced by the fluid flow, producing an asymmetrical morphology that the dendrite grows faster in the upstream direction, whereas largely slower in the downstream direction. The growth process of dendritic side-branches is modeled in a high settling velocity without any artificial noise introduced. The melt flow triggered by the dendrite motion enhances the growth of the dendrite in the downward direction, which in turn influences the subsequent dendritic translation.Background γ-Glutamyltransferase (GGT) is a marker of oxidative stress. Elevated serum GGT is linked to poor survival in various malignancies; however, there are no data on metastatic renal cell carcinoma (****). Additionally, GGT expression in cancer tissues remains largely unknown. Objective The present study was designed to determine the prognostic role of serum GGT in patients with **** and the association between systemic and local GGT levels. Patients and methods Pretherapeutic serum GGT and other clinicopathological parameters were retrospectively compared with overall survival (OS) in 146 consecutive patients with **** receiving tyrosine kinase inhibitor therapy. https://www.selleckchem.com/products/8-bromo-camp.html GGT expression was analyzed in 65 resected specimens using immunohistochemistry. Results A total of 82 patients (56%) died during the follow-up period (median 34.9 months). Median OS was 16.0 months and 36.8 months in patients with elevated GGT levels and without elevated GGT, respectively (P less then 0.001). On multivariable analysis, elevated serum GGT was an independent adverse prognostic factor (hazard ratio [HR] 4.04, P less then 0.001), together with high neutrophils (HR 2.06, P = 0.041), low albumin (HR 2.00, P = 0.006), high lactate dehydrogenase (HR 2.68, P less then 0.001), and high De Ritis ratio (HR 1.97, P = 0.004). Preoperative serum GGT levels were 29, 48, and 109 U/l in patients whose renal cancer cells showed negative to weak, moderate, and strong GGT expression, respectively (P = 0.004). Conclusions Elevated serum GGT was an unfavorable prognostic factor in ****, and overexpression of GGT in renal cancer cells might be responsible for elevation of serum GGT.Since December 2019, a novel Coronavirus (SARS-CoV-2) was confirmed as the etiologic agent of a worldwide outbreak of a pneumonia that can result in severe respiratory failure. This clinical entity seems to be associated with a marked hypercoagulable state that causes both arterial and venous thromboembolic complications. Therefore, an adequate anti-thrombotic prophylaxis is recommended in hospitalized COVID-19 patients. Although rapidly worsening respiratory symptoms in a patient with SARS-CoV-2 respiratory infection may correlate with worsening pneumonia itself, it may also mask a pulmonary embolism. We report the case of a 50-year-old man affected by SARS-CoV-2 pneumonia, who developed acute pulmonary embolism.Tunnel ventilation is an increasingly popular approach to mitigate the effects of heat stress on dairy cattle. Tunnel-ventilation barns use a bank of high-power fans to move air horizontally from one end of the barn to the other at *** level. The overall objective of the present experiments was to determine whether tunnel ventilation is superior to housing with fans and sprinklers with respect to rectal temperature during heat stress and seasonal variation in milk yield. In the first study, rectal temperatures were measured for 1097 lactating Holstein cows in six freestall barns with fans and sprinklers and 575 lactating Holsteins in four tunnel-ventilated freestall barns at a time point between 1400 and 1600 h during the months of June to August in Florida, USA. Rectal temperatures were lower for cows in tunnel-ventilation barns than sprinkler-and-fan barns when the tunnel-ventilation barns were built de novo but not when the tunnel-ventilation barns were produced by retrofitting a sprinkler-and-fan barn (interaction, P = 0.
    The use of "omics" is increasing in research areas looking to identify biomarkers or early preclinical signs of disease or to increase understanding of complex pathological processes that determines prognosis of the disease. Diabetic kidney disease is no exception as it is an area in need of further improvement of both understanding and prognosis. In addition, there is a notion that pretreatment investigations using techniques like proteomics, lipidomics and metabolomics can help individualize therapy thus fulfilling the wish for personalized medicine. An increasing number of cohort studies using these techniques are published, but only few have been validated in external cohorts or even replicated by other groups. In essence, to achieve clinical impact and usefulness, prospective validation is needed. So far, only the urinary proteomics based PRIORITY study has tried to do this, as discussed in this review. Other areas are promising, but are currently lacking such efforts. In this review we report and discuss the current status of urinary proteomics as well as plasma metabolomics and lipidomics with an overview of the results so far, and with some comments and perspectives regarding future developments and implementation. As is evident, these techniques are promising, but there is still some way before widespread clinical use can be foreseen.We investigated the potential role of miR-490-3p in ischemia reperfusion (IR) injury. We first determined the expression of miR-490-3p and autophagy-related 4B cysteine (ATG4B) in IR. Then, to explore whether miR-490-3p would affect autophagy, apoptosis, and IR injury, we evaluated apoptosis, autophagy, and infarct size via gain- and loss-of-function experiments. Furthermore, we used adenovirus to enhance or inhibit the expression of ATG4B, and then measured autophagy, apoptosis, and IR injury. miR-490-3p was downregulated in the hearts during the process of IR, while ATG4B was upregulated. The inhibition of miR-490-3p or overexpression of ATG4B could promote the expression of LC3II, increase the autolysosomes, inhibit the expression of p62, and reduce infarct size. On all accounts, the inhibition of miR-490-3p could promote autophagy to reduce myocardial IR injury by upregulating ATG4B, a finding that provides new insights for the protective mechanism of autophagy in IR. Graphical Abstract.A two-dimensional model is developed to simulate dendrite growth and movement in a gravity environment. The model combines the features of cellular automaton and lattice Boltzmann methods. Two sets of distribution functions are adopted to calculate the melt flow and solute transport simultaneously. The fluid force acting on the dendrite is calculated by extending the basic flow simulation at the solid-liquid interface. Incorporating the force interaction between melt flow and solidified dendrite into the algorithm for dendritic growth, the movement of a growing dendrite in the flowing melt can be simulated. After model validation, the coupled model has been applied to simulate the evolution and motion of an individual nucleus that grows into a dendrite in the presence of gravitational force. It is found that the dendrite growth is strongly influenced by the fluid flow, producing an asymmetrical morphology that the dendrite grows faster in the upstream direction, whereas largely slower in the downstream direction. The growth process of dendritic side-branches is modeled in a high settling velocity without any artificial noise introduced. The melt flow triggered by the dendrite motion enhances the growth of the dendrite in the downward direction, which in turn influences the subsequent dendritic translation.Background γ-Glutamyltransferase (GGT) is a marker of oxidative stress. Elevated serum GGT is linked to poor survival in various malignancies; however, there are no data on metastatic renal cell carcinoma (mRCC). Additionally, GGT expression in cancer tissues remains largely unknown. Objective The present study was designed to determine the prognostic role of serum GGT in patients with mRCC and the association between systemic and local GGT levels. Patients and methods Pretherapeutic serum GGT and other clinicopathological parameters were retrospectively compared with overall survival (OS) in 146 consecutive patients with mRCC receiving tyrosine kinase inhibitor therapy. https://www.selleckchem.com/products/8-bromo-camp.html GGT expression was analyzed in 65 resected specimens using immunohistochemistry. Results A total of 82 patients (56%) died during the follow-up period (median 34.9 months). Median OS was 16.0 months and 36.8 months in patients with elevated GGT levels and without elevated GGT, respectively (P less then 0.001). On multivariable analysis, elevated serum GGT was an independent adverse prognostic factor (hazard ratio [HR] 4.04, P less then 0.001), together with high neutrophils (HR 2.06, P = 0.041), low albumin (HR 2.00, P = 0.006), high lactate dehydrogenase (HR 2.68, P less then 0.001), and high De Ritis ratio (HR 1.97, P = 0.004). Preoperative serum GGT levels were 29, 48, and 109 U/l in patients whose renal cancer cells showed negative to weak, moderate, and strong GGT expression, respectively (P = 0.004). Conclusions Elevated serum GGT was an unfavorable prognostic factor in mRCC, and overexpression of GGT in renal cancer cells might be responsible for elevation of serum GGT.Since December 2019, a novel Coronavirus (SARS-CoV-2) was confirmed as the etiologic agent of a worldwide outbreak of a pneumonia that can result in severe respiratory failure. This clinical entity seems to be associated with a marked hypercoagulable state that causes both arterial and venous thromboembolic complications. Therefore, an adequate anti-thrombotic prophylaxis is recommended in hospitalized COVID-19 patients. Although rapidly worsening respiratory symptoms in a patient with SARS-CoV-2 respiratory infection may correlate with worsening pneumonia itself, it may also mask a pulmonary embolism. We report the case of a 50-year-old man affected by SARS-CoV-2 pneumonia, who developed acute pulmonary embolism.Tunnel ventilation is an increasingly popular approach to mitigate the effects of heat stress on dairy cattle. Tunnel-ventilation barns use a bank of high-power fans to move air horizontally from one end of the barn to the other at cow level. The overall objective of the present experiments was to determine whether tunnel ventilation is superior to housing with fans and sprinklers with respect to rectal temperature during heat stress and seasonal variation in milk yield. In the first study, rectal temperatures were measured for 1097 lactating Holstein cows in six freestall barns with fans and sprinklers and 575 lactating Holsteins in four tunnel-ventilated freestall barns at a time point between 1400 and 1600 h during the months of June to August in Florida, USA. Rectal temperatures were lower for cows in tunnel-ventilation barns than sprinkler-and-fan barns when the tunnel-ventilation barns were built de novo but not when the tunnel-ventilation barns were produced by retrofitting a sprinkler-and-fan barn (interaction, P = 0.
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