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  • The birth of a child affected by a threatened abortion (TAB) in utero is associated with autism spectrum disorder; association with other neurological disorders is unknown.

    This nationwide registry-based cohort study included singletons live-born in Denmark (1979-2010), followed through 2016. The outcomes were epilepsy, cerebral palsy (CP) and attention-deficit/hyperactivity disorder (ADHD). We used Cox regression to compute hazard ratios (HRs), adjusted for birth year, birth order, parental age, morbidity, medication use and maternal socio-economic factors. To remove time-invariant family-shared confounding, we applied sibling analyses.

    The study population included 1 864 221 singletons live-born in 1979-2010. Among the TAB-affected children (N = 59 134) vs TAB-unaffected children, at the end of follow-up, the cumulative incidence was 2.2% vs 1.6% for epilepsy, 0.4% vs 0.2% for CP and 5.5% vs 4.2% for ADHD (for children born in 1995-2010). The adjusted HRs were 1.25 [95% confidence interval (CI) 1.16-1.34] for epilepsy, 1.42 (95% CI 1.20-1.68) for CP and 1.21 (95% CI 1.14-1.29) for ADHD. In the sibling design, the adjusted HRs were unity for epilepsy (full siblings 0.96, 95% CI 0.82-1.12; maternal 1.04, 95% CI 0.90-1.20; paternal 1.08, 95% CI 0.93-1.25) and ADHD (full 1.08, 95% CI 0.92-1.27; maternal 1.04, 95% CI 0.90-1.20; paternal 1.08, 95% CI 0.93-1.25). For CP, HRs shifted away from unity among sibling pairs (full 2.92, 95% CI 1.33-6.39; maternal 2.03, 95% CI 1.15-3.57; paternal 3.28, 95% CI 1.36-7.91).

    The birth of a child affected by TAB in utero was associated with a greater risk of CP, but not epilepsy or ADHD.
    The birth of a child affected by TAB in utero was associated with a greater risk of CP, but not epilepsy or ADHD.
    COVID-19 has strained healthcare systems with patient hospitalizations and deaths. Anti-spike monoclonal antibodies, including bamlanivimab, have demonstrated reduction in hospitalization rates in clinical trials, yet real-world evidence is lacking.

    We conducted a retrospective case-control study across a single healthcare system of non-hospitalized patients, age 18 years or older, with documented positive SARS-CoV-2 testing, risk factors for severe COVID-19, and referrals for bamlanivimab via emergency use authorization. Cases were defined as patients who received bamlanivimab; contemporary controls had a referral order placed but did not receive bamlanivimab. The primary outcome was 30-day hospitalization rate from initial positive SARS-CoV-2 PCR. Descriptive statistics, including Chi-square and Mann-Whitney U test, were performed. Multivariable logistic regression was used for adjusted analysis to evaluate independent associations with 30-day hospitalization.

    Between November 20, 2020 and January 19,gainst hospitalization.
    Approximately 7.3 million births occur annually among adolescents in low- and middle-income countries. Pregnant adolescents constitute a nutritionally vulnerable group that could benefit from intervention to mitigate the mortality and adverse birth outcomes associated with adolescent pregnancy.

    The aim of this systematic review and meta-analysis was to assess the following (1) the effect of multiple-micronutrient (MMN) supplementation vs iron and folic acid (IFA) supplementation among adolescents on maternal morbidity, birth outcomes, and mortality outcomes, (2) the effects of MMN supplementation in adolescents compared with the effects in adult women, and (3) the effect modification, if any, of MMN supplementation by baseline and geographic characteristics of adolescents.

    MEDLINE and Cochrane databases were searched, along with the reference lists of relevant reviews.

    Multiple-micronutrient supplementation trials in pregnancy that were conducted in a low- or middle-income country and had included at .95) when compared with IFA supplementation. The effects of MMN supplementation did not differ between adolescents and older women, although a potentially greater reduction in small-for-gestational-age births was observed among adolescents. Effect modification by baseline characteristics and geographic region was inconclusive.

    Multiple-micronutrient supplementation can improve birth outcomes among pregnant adolescents in low- and middle-income countries. Policy related to antenatal care in these settings should prioritize MMN supplementation over the currently recommended IFA supplementation for all pregnant women, especially adolescents.
    Multiple-micronutrient supplementation can improve birth outcomes among pregnant adolescents in low- and middle-income countries. Policy related to antenatal care in these settings should prioritize MMN supplementation over the currently recommended IFA supplementation for all pregnant women, especially adolescents.
    To assess potential benefits of a local activation time (LAT) automatic acquisition protocol using wavefront annotation plus an ECG pattern matching algorithm [automatic (AUT)-arm] during premature ventricular complex (PVC) ablation procedures.

    Prospective, randomized, controlled, and international multicentre study (NCT03340922). One hundred consecutive patients with indication for PVC ablation were enrolled and randomized to AUT (n = 50) or manual (MAN, n = 50) annotation protocols using the CARTO3 navigation system. The primary endpoint was mapping success. Clinical success was defined as a PVC-burden reduction of ≥80% in the 24-h Holter within 6 months after the procedure. Mean age was 56 ± 14 years, 54% men. The mean baseline PVC burden was 25 ± 13%, and mean left ventricular ejection fraction (LVEF) 55 ± 11%. Baseline characteristics were similar between the groups. The most frequent PVC-site of origin were right ventricular outflow tract (41%), LV (25%), and left ventricular outflow tract (17%), without differences between groups. Radiofrequency (RF) time and number of RF applications were similar for both groups. Mapping and procedure times were significantly shorter in the AUT-arm (25.5 ± 14.3 vs. 32.8 ± 12.6 min, P = 0.009; and 54.8 ± 24.8 vs. 67.4 ± 25.2, P = 0.014, respectively), while more mapping points were acquired [136 (94-222) AUT vs. https://www.selleckchem.com/products/rg2833-rgfp109.html 79 (52-111) MAN; P < 0.001]. Mapping and clinical success were similar in both groups. There were no procedure-related complications.

    The use of a complete automatic protocol for LAT annotation during PVC ablation procedures allows to achieve similar clinical endpoints with higher procedural efficiency when compared with conventional, manual annotation carried out by expert operators.
    The use of a complete automatic protocol for LAT annotation during PVC ablation procedures allows to achieve similar clinical endpoints with higher procedural efficiency when compared with conventional, manual annotation carried out by expert operators.
    The birth of a child affected by a threatened abortion (TAB) in utero is associated with autism spectrum disorder; association with other neurological disorders is unknown. This nationwide registry-based cohort study included singletons live-born in Denmark (1979-2010), followed through 2016. The outcomes were epilepsy, cerebral palsy (CP) and attention-deficit/hyperactivity disorder (ADHD). We used Cox regression to compute hazard ratios (HRs), adjusted for birth year, birth order, parental age, morbidity, medication use and maternal socio-economic factors. To remove time-invariant family-shared confounding, we applied sibling analyses. The study population included 1 864 221 singletons live-born in 1979-2010. Among the TAB-affected children (N = 59 134) vs TAB-unaffected children, at the end of follow-up, the cumulative incidence was 2.2% vs 1.6% for epilepsy, 0.4% vs 0.2% for CP and 5.5% vs 4.2% for ADHD (for children born in 1995-2010). The adjusted HRs were 1.25 [95% confidence interval (CI) 1.16-1.34] for epilepsy, 1.42 (95% CI 1.20-1.68) for CP and 1.21 (95% CI 1.14-1.29) for ADHD. In the sibling design, the adjusted HRs were unity for epilepsy (full siblings 0.96, 95% CI 0.82-1.12; maternal 1.04, 95% CI 0.90-1.20; paternal 1.08, 95% CI 0.93-1.25) and ADHD (full 1.08, 95% CI 0.92-1.27; maternal 1.04, 95% CI 0.90-1.20; paternal 1.08, 95% CI 0.93-1.25). For CP, HRs shifted away from unity among sibling pairs (full 2.92, 95% CI 1.33-6.39; maternal 2.03, 95% CI 1.15-3.57; paternal 3.28, 95% CI 1.36-7.91). The birth of a child affected by TAB in utero was associated with a greater risk of CP, but not epilepsy or ADHD. The birth of a child affected by TAB in utero was associated with a greater risk of CP, but not epilepsy or ADHD. COVID-19 has strained healthcare systems with patient hospitalizations and deaths. Anti-spike monoclonal antibodies, including bamlanivimab, have demonstrated reduction in hospitalization rates in clinical trials, yet real-world evidence is lacking. We conducted a retrospective case-control study across a single healthcare system of non-hospitalized patients, age 18 years or older, with documented positive SARS-CoV-2 testing, risk factors for severe COVID-19, and referrals for bamlanivimab via emergency use authorization. Cases were defined as patients who received bamlanivimab; contemporary controls had a referral order placed but did not receive bamlanivimab. The primary outcome was 30-day hospitalization rate from initial positive SARS-CoV-2 PCR. Descriptive statistics, including Chi-square and Mann-Whitney U test, were performed. Multivariable logistic regression was used for adjusted analysis to evaluate independent associations with 30-day hospitalization. Between November 20, 2020 and January 19,gainst hospitalization. Approximately 7.3 million births occur annually among adolescents in low- and middle-income countries. Pregnant adolescents constitute a nutritionally vulnerable group that could benefit from intervention to mitigate the mortality and adverse birth outcomes associated with adolescent pregnancy. The aim of this systematic review and meta-analysis was to assess the following (1) the effect of multiple-micronutrient (MMN) supplementation vs iron and folic acid (IFA) supplementation among adolescents on maternal morbidity, birth outcomes, and mortality outcomes, (2) the effects of MMN supplementation in adolescents compared with the effects in adult women, and (3) the effect modification, if any, of MMN supplementation by baseline and geographic characteristics of adolescents. MEDLINE and Cochrane databases were searched, along with the reference lists of relevant reviews. Multiple-micronutrient supplementation trials in pregnancy that were conducted in a low- or middle-income country and had included at .95) when compared with IFA supplementation. The effects of MMN supplementation did not differ between adolescents and older women, although a potentially greater reduction in small-for-gestational-age births was observed among adolescents. Effect modification by baseline characteristics and geographic region was inconclusive. Multiple-micronutrient supplementation can improve birth outcomes among pregnant adolescents in low- and middle-income countries. Policy related to antenatal care in these settings should prioritize MMN supplementation over the currently recommended IFA supplementation for all pregnant women, especially adolescents. Multiple-micronutrient supplementation can improve birth outcomes among pregnant adolescents in low- and middle-income countries. Policy related to antenatal care in these settings should prioritize MMN supplementation over the currently recommended IFA supplementation for all pregnant women, especially adolescents. To assess potential benefits of a local activation time (LAT) automatic acquisition protocol using wavefront annotation plus an ECG pattern matching algorithm [automatic (AUT)-arm] during premature ventricular complex (PVC) ablation procedures. Prospective, randomized, controlled, and international multicentre study (NCT03340922). One hundred consecutive patients with indication for PVC ablation were enrolled and randomized to AUT (n = 50) or manual (MAN, n = 50) annotation protocols using the CARTO3 navigation system. The primary endpoint was mapping success. Clinical success was defined as a PVC-burden reduction of ≥80% in the 24-h Holter within 6 months after the procedure. Mean age was 56 ± 14 years, 54% men. The mean baseline PVC burden was 25 ± 13%, and mean left ventricular ejection fraction (LVEF) 55 ± 11%. Baseline characteristics were similar between the groups. The most frequent PVC-site of origin were right ventricular outflow tract (41%), LV (25%), and left ventricular outflow tract (17%), without differences between groups. Radiofrequency (RF) time and number of RF applications were similar for both groups. Mapping and procedure times were significantly shorter in the AUT-arm (25.5 ± 14.3 vs. 32.8 ± 12.6 min, P = 0.009; and 54.8 ± 24.8 vs. 67.4 ± 25.2, P = 0.014, respectively), while more mapping points were acquired [136 (94-222) AUT vs. https://www.selleckchem.com/products/rg2833-rgfp109.html 79 (52-111) MAN; P < 0.001]. Mapping and clinical success were similar in both groups. There were no procedure-related complications. The use of a complete automatic protocol for LAT annotation during PVC ablation procedures allows to achieve similar clinical endpoints with higher procedural efficiency when compared with conventional, manual annotation carried out by expert operators. The use of a complete automatic protocol for LAT annotation during PVC ablation procedures allows to achieve similar clinical endpoints with higher procedural efficiency when compared with conventional, manual annotation carried out by expert operators.
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  • 38, 95% confidence interval -2.53 to -0.24; P = 0.02), while pulmonary artery banding was a significant risk factor for elevated pre-Fontan mean pulmonary artery pressure (Coefficient B 1.68, 95% confidence interval 0.81 to 2.56, P < 0.001).

    High mean pulmonary artery pressure before bidirectional cavopulmoary shunt (≥16mmHg) remains a significant risk factor for adverse events after TCPC even though mean pulmonary artery pressure decreased below 10 mmHg before TCPC.
    High mean pulmonary artery pressure before bidirectional cavopulmoary shunt (≥16mmHg) remains a significant risk factor for adverse events after TCPC even though mean pulmonary artery pressure decreased below 10 mmHg before TCPC.Attenuation of the secondary injury of spinal cord injury (SCI) can suppress the spread of spinal cord tissue damage, possibly resulting in spinal cord sparing that can improve functional prognoses. Granulocyte colony-stimulating factor (G-CSF) is a haematological cytokine commonly used to treat neutropenia. Previous reports have shown that G-CSF promotes functional recovery in rodent models of SCI. Based on preclinical results, we conducted early phase clinical trials, showing safety/feasibility and suggestive efficacy. These lines of evidence demonstrate that G-CSF might have therapeutic benefits for acute SCI in humans. To confirm this efficacy and to obtain strong evidence for pharmaceutical approval of G-CSF therapy for SCI, we conducted a phase 3 clinical trial designed as a prospective, randomized, double-blinded and placebo-controlled comparative trial. The current trial included cervical SCI [severity of American Spinal Injury Association (ASIA) Impairment Scale (AIS) B or C] within 48 h after injuryhs (P = 0.062) and 1 year (P = 0.073) after drug administration tend to be higher in the G-CSF group compared with the placebo control group. Moreover, in patients aged over 65 years old, motor recovery 6 months after drug administration showed a strong trend towards a better recovery in the G-CSF treated group (P = 0.056) compared with the control group. https://www.selleckchem.com/products/pf-3644022.html The present trial failed to show a significant effect of G-CSF in primary end point although the subanalyses of the present trial suggested potential G-CSF benefits for specific population.Healthy function of intervertebral discs (IVDs) depends on their tissue mechanical properties. Native cells embedded within IVD tissues are responsible for building, maintaining, and repairing IVD structures in response to genetic, biochemical, and mechanical signals. Organ culturing provides a method for investigating how cells respond to these stimuli in their natural architectural environment. The purpose of this study was to determine how organ culturing affects the mechanical characteristics of functional spine units (FSUs) across the entire range of axial loading, including the neutral zone (NZ), using a rat tail model. Rat tail FSUs were organ cultured at 37 °C in an unloaded state in standard culture media for either 1-day (n = 8) or 6-days (n = 12). Noncultured FSUs (n = 12) were included as fresh control specimens. Axial mechanical properties were tested by applying cyclical compression and tension. A novel mathematical approach was developed to fully characterize the relationship between load, stiffness, and deformation through the entire range of loading. Culturing FSUs for 1-day did not affect any of the axial mechanical outcome measures compared to noncultured IVDs; however, culturing for 6 days increased the size of NZ by 112% and decreased the stiffness in NZ, compressive, and tensile regions by 53%, 19%, and 15%, respectively, compared to noncultured FSUs. These results highlight the importance of considering how the mechanical integrity of IVD tissues may affect the transmission of mechanical signals to cells in unloaded organ culturing experiments.
    The host's immune response to malignant tumor is fundamental to tumorigenesis and tumor development. The immune score is currently used to assess prognosis and to guide immunotherapy; however, its association with lung cancer prognosis is not clear.

    Clinical features and immune score data of lung cancer patients from The Cancer Genome Atlas were obtained to build a clinical prognosis nomogram. The model's accuracy was verified by calibration curves.

    In total, 1005 patients with lung cancer were included. Patients were divided into three groups according to low, medium, and high immune scores. Compared with patients in the low immune score group, the disease-free survival (DFS) of patients in medium and high immune score groups was significantly longer; the hazard ratio (HR) and 95% confidence interval (95% CI) were 0.77 [0.60-0.99] and 0.74 [0.60-0.91], respectively. The overall survival (OS) of patients in the medium and high immune score groups was significantly longer than in the low immune score group; the HR and 95% CI were 0.74 [0.57-0.96] and 0.69 [0.55-0.88], respectively. A clinical prediction model was established to predict the survival prognosis. As verified by calibration curves, the model showed good predictive ability, especially for predicting 3-/5-year DFS and OS.

    Patients with lung cancer with medium and high immune scores had longer DFS and OS than those in low immune score group. Patient prognosis can be effectively predicted by the clinical prediction model combining clinical features and immune score and was consistent with actual clinical outcomes.
    Patients with lung cancer with medium and high immune scores had longer DFS and OS than those in low immune score group. Patient prognosis can be effectively predicted by the clinical prediction model combining clinical features and immune score and was consistent with actual clinical outcomes.Promyelocytic leukemia protein (PML) is a constitutive component of PML nuclear bodies (PML-NBs), which function as stress-regulated SUMOylation factories. Since PML can also act as a regulator of the inflammatory and fibroproliferative responses characteristic of atherosclerosis, we investigated whether PML is implicated in this disease. Immunoblotting, ELISA and immunohistochemistry showed a stronger expression of PML in segments of human atherosclerotic coronary arteries and sections compared with non-atherosclerotic ones. In particular, PML was concentrated in PML-NBs from α-smooth muscle actin (α-SMA)-immunoreactive cells in plaque areas. To identify possible functional consequences of PML-accumulation in this cell type, differentiated human coronary artery smooth muscle cells (dHCASMCs) were transfected with a vector containing the intact PML-gene. These PML-transfected dHCASMCs showed higher levels of small ubiquitin-like modifier (SUMO)-1-dependent SUMOylated proteins, but lower levels of markers for smooth muscle cell (SMC) differentiation and revealed more proliferation and migration activities than dHCASMCs transfected with the vector lacking a specific gene insert or with the vector containing a mutated PML-gene coding for a PML-form without SUMOylation activity.
    38, 95% confidence interval -2.53 to -0.24; P = 0.02), while pulmonary artery banding was a significant risk factor for elevated pre-Fontan mean pulmonary artery pressure (Coefficient B 1.68, 95% confidence interval 0.81 to 2.56, P < 0.001). High mean pulmonary artery pressure before bidirectional cavopulmoary shunt (≥16mmHg) remains a significant risk factor for adverse events after TCPC even though mean pulmonary artery pressure decreased below 10 mmHg before TCPC. High mean pulmonary artery pressure before bidirectional cavopulmoary shunt (≥16mmHg) remains a significant risk factor for adverse events after TCPC even though mean pulmonary artery pressure decreased below 10 mmHg before TCPC.Attenuation of the secondary injury of spinal cord injury (SCI) can suppress the spread of spinal cord tissue damage, possibly resulting in spinal cord sparing that can improve functional prognoses. Granulocyte colony-stimulating factor (G-CSF) is a haematological cytokine commonly used to treat neutropenia. Previous reports have shown that G-CSF promotes functional recovery in rodent models of SCI. Based on preclinical results, we conducted early phase clinical trials, showing safety/feasibility and suggestive efficacy. These lines of evidence demonstrate that G-CSF might have therapeutic benefits for acute SCI in humans. To confirm this efficacy and to obtain strong evidence for pharmaceutical approval of G-CSF therapy for SCI, we conducted a phase 3 clinical trial designed as a prospective, randomized, double-blinded and placebo-controlled comparative trial. The current trial included cervical SCI [severity of American Spinal Injury Association (ASIA) Impairment Scale (AIS) B or C] within 48 h after injuryhs (P = 0.062) and 1 year (P = 0.073) after drug administration tend to be higher in the G-CSF group compared with the placebo control group. Moreover, in patients aged over 65 years old, motor recovery 6 months after drug administration showed a strong trend towards a better recovery in the G-CSF treated group (P = 0.056) compared with the control group. https://www.selleckchem.com/products/pf-3644022.html The present trial failed to show a significant effect of G-CSF in primary end point although the subanalyses of the present trial suggested potential G-CSF benefits for specific population.Healthy function of intervertebral discs (IVDs) depends on their tissue mechanical properties. Native cells embedded within IVD tissues are responsible for building, maintaining, and repairing IVD structures in response to genetic, biochemical, and mechanical signals. Organ culturing provides a method for investigating how cells respond to these stimuli in their natural architectural environment. The purpose of this study was to determine how organ culturing affects the mechanical characteristics of functional spine units (FSUs) across the entire range of axial loading, including the neutral zone (NZ), using a rat tail model. Rat tail FSUs were organ cultured at 37 °C in an unloaded state in standard culture media for either 1-day (n = 8) or 6-days (n = 12). Noncultured FSUs (n = 12) were included as fresh control specimens. Axial mechanical properties were tested by applying cyclical compression and tension. A novel mathematical approach was developed to fully characterize the relationship between load, stiffness, and deformation through the entire range of loading. Culturing FSUs for 1-day did not affect any of the axial mechanical outcome measures compared to noncultured IVDs; however, culturing for 6 days increased the size of NZ by 112% and decreased the stiffness in NZ, compressive, and tensile regions by 53%, 19%, and 15%, respectively, compared to noncultured FSUs. These results highlight the importance of considering how the mechanical integrity of IVD tissues may affect the transmission of mechanical signals to cells in unloaded organ culturing experiments. The host's immune response to malignant tumor is fundamental to tumorigenesis and tumor development. The immune score is currently used to assess prognosis and to guide immunotherapy; however, its association with lung cancer prognosis is not clear. Clinical features and immune score data of lung cancer patients from The Cancer Genome Atlas were obtained to build a clinical prognosis nomogram. The model's accuracy was verified by calibration curves. In total, 1005 patients with lung cancer were included. Patients were divided into three groups according to low, medium, and high immune scores. Compared with patients in the low immune score group, the disease-free survival (DFS) of patients in medium and high immune score groups was significantly longer; the hazard ratio (HR) and 95% confidence interval (95% CI) were 0.77 [0.60-0.99] and 0.74 [0.60-0.91], respectively. The overall survival (OS) of patients in the medium and high immune score groups was significantly longer than in the low immune score group; the HR and 95% CI were 0.74 [0.57-0.96] and 0.69 [0.55-0.88], respectively. A clinical prediction model was established to predict the survival prognosis. As verified by calibration curves, the model showed good predictive ability, especially for predicting 3-/5-year DFS and OS. Patients with lung cancer with medium and high immune scores had longer DFS and OS than those in low immune score group. Patient prognosis can be effectively predicted by the clinical prediction model combining clinical features and immune score and was consistent with actual clinical outcomes. Patients with lung cancer with medium and high immune scores had longer DFS and OS than those in low immune score group. Patient prognosis can be effectively predicted by the clinical prediction model combining clinical features and immune score and was consistent with actual clinical outcomes.Promyelocytic leukemia protein (PML) is a constitutive component of PML nuclear bodies (PML-NBs), which function as stress-regulated SUMOylation factories. Since PML can also act as a regulator of the inflammatory and fibroproliferative responses characteristic of atherosclerosis, we investigated whether PML is implicated in this disease. Immunoblotting, ELISA and immunohistochemistry showed a stronger expression of PML in segments of human atherosclerotic coronary arteries and sections compared with non-atherosclerotic ones. In particular, PML was concentrated in PML-NBs from α-smooth muscle actin (α-SMA)-immunoreactive cells in plaque areas. To identify possible functional consequences of PML-accumulation in this cell type, differentiated human coronary artery smooth muscle cells (dHCASMCs) were transfected with a vector containing the intact PML-gene. These PML-transfected dHCASMCs showed higher levels of small ubiquitin-like modifier (SUMO)-1-dependent SUMOylated proteins, but lower levels of markers for smooth muscle cell (SMC) differentiation and revealed more proliferation and migration activities than dHCASMCs transfected with the vector lacking a specific gene insert or with the vector containing a mutated PML-gene coding for a PML-form without SUMOylation activity.
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  • The cell cycle is a highly regulated and evolutionary conserved process that results in the duplication of cell content and the equal distribution of the duplicated chromosomes into a pair of daughter cells. Histones are fundamental structural components of chromatin in eukaryotic cells, and their post-translational modifications (PTMs) benchmark DNA readout and chromosome condensation. Aberrant regulation of the cell cycle associated with dysregulation of histone PTMs is the cause of critical diseases such as cancer. Monitoring changes of histone PTMs could pave the way to understanding the molecular mechanisms associated with epigenetic regulation of cell proliferation. Previously, our lab established a novel middle-down workflow using porous graphitic carbon (PGC) as a stationary phase to analyze histone PTMs, which utilizes the same reversed-phase chromatography for gradient separation as canonical proteomics coupled with online mass spectrometry (MS). Here, we applied this novel workflow for high-throughput analysis of histone modifications of H3.1 and H3.2 during the cell cycle. Collectively, we identified 1133 uniquely modified canonical histone H3 N-terminal tails. Consistent with previous findings, histone H3 phosphorylation increased significantly during the mitosis (M) phase. Histone H3 variant-specific and cell-cycle-dependent expressions of PTMs were observed, underlining the need to not combine H3.1 and H3.2 together as H3. We confirmed previously known H3 PTM crosstalk (e.g., K9me-S10ph) and revealed new information in this area as well. https://www.selleckchem.com/products/a-1210477.html These findings imply that the combinatorial PTMs play a role in cell cycle control, and they may serve as markers for proliferation.Coal and coal gangue spontaneous combustion (CGSC) occurs globally, causing significant environmental pollution. However, its emissions are poorly quantified and are overlooked in global or regional air pollutant emission inventories in previous studies, resulting in the underestimation of its impacts on climate, environment, and public health. This study quantified the emissions of various air pollutants originating from CGSC in Wuhai, a city in China, investigated emission characteristics, and estimated the contribution of CGSC emissions to fine particulate matter (PM2.5) air pollution and related health impacts on a regional scale. The results revealed that the CGSC-related PM2.5 emissions were approximately 4643 t a-1 (95% confidence interval (95% CI) 721; 10447), accounting for 26.3% of the total PM2.5 emissions. Alkanes, alkenes, and aromatics accounted for 69.4, 17.9, and 2.9%, respectively, of the total emissions of volatile organic compounds (VOCs). Due to CGSC emissions, the ambient PM2.5 concentration in Wuhai increased by 5.7 μg m-3 on average, while the nitrate concentration decreased. The number of premature deaths caused by exposure to ambient PM2.5 associated with CGSC reached 381 (95% CI 290; 452) in Wuhai and surrounding cities in 2017. Urgent control strategies and engineering techniques are needed to mitigate CGSC to protect public health.The directional flexibility of proteins is an equilibrium molecular property which is accessible to both experiment and computation. Single molecule force spectroscopy (SMFS) experiments report effective directional spring constants to describe the collective anisotropic response of a protein structure to mechanical pulling forces applied along selected axes. On the other hand, computational methods have thus far employed either indirect force based nonequilibrium simulations or coarse-grained elastic network models (ENM) to predict protein directional spring constants. Here, we examine the ability of equilibrium atomistic Molecular Dynamics (MD) simulations to estimate the directional flexibility and mechanical anisotropy of proteins. MD-derived effective directional spring constants are found to correlate well with SMFS spring constants (ρ2 = 0.97-0.99; Adj R2 = 0.92-0.99) and unfolding forces (ρ2 = 0.85-0.97; Adj R2 = 0.63-0.91) for five different globular proteins. Specifically, the computed spring consta85 bond vectors in Ub, we propose and validate a new covariance-propagation scheme to extract spring constants from ENM normal modes. We also critically examine the ability of ENM to predict directional flexibility of proteins and suggest modifications to improve these intuitive and scalable descriptions.Major strides have been made in the development of materials and devices based around low-dimensional hybrid group 14 metal halide perovskites. Thus far, this work has mostly focused on compounds containing highly toxic Pb, with the analogous less toxic Sn materials being comparatively poorly evolved. In response, the study herein aims to (i) provide insight into the impact of templating cations upon the structure of n = 1 2D tin iodide perovskites (where n refers to the number of contiguous two-dimensional (2D) inorganic layers, i.e., not separated by organic cations) and (ii) examine their potential as light absorbers for photovoltaic (PV) cells. It was discovered through systematic tuning of organic dications that imidazolium rings are able to induce the formation of (110)-oriented materials, including examples of "3 × 3" corrugated Sn-I perovskites. This structural outcome is a consequence of a combination of supramolecular interactions of the two endocyclic N atoms of the imidazolium rings with the Sn-I ng lead iodide material, which demonstrates that 2D Sn-based materials have significant potential as less toxic alternatives to their Pb counterparts.Monophosphate, an essential component of nucleic acids, as well as cell membranes and signaling molecules, is often bound to metal cations. Despite the biological importance of monophosphate-containing cell-signaling or lipid molecules, their propensity to bind the two most abundant cellular dications, Mg2+ and Ca2+, in a particular mode (inner/outer shell, mono/bidentate) is not well understood. Whether they prefer binding to Mg2+ than to Ca2+ and if they can outcompete the carboxylates of excitatory Asp/Glu and inhibitory gamma-aminobutyric acid (GABA) neurotransmitters in binding to Mg2+/Ca2+ remain unclear. To address these questions, we modeled cyclic adenosine/guanosine monophosphate (cAMP/cGMP), nucleoside 2',3'-cyclic phosphate, phosphatidylinositol (PI), phosphatidylserine (PS), and phosphatidylethanolamine (PEA) and determined their most stable metal-binding modes, including those of Asp/Glu and GABA, as well as their selectivity for Mg2+/Ca2+ using density functional theory combined with the polarizable continuum model.
    The cell cycle is a highly regulated and evolutionary conserved process that results in the duplication of cell content and the equal distribution of the duplicated chromosomes into a pair of daughter cells. Histones are fundamental structural components of chromatin in eukaryotic cells, and their post-translational modifications (PTMs) benchmark DNA readout and chromosome condensation. Aberrant regulation of the cell cycle associated with dysregulation of histone PTMs is the cause of critical diseases such as cancer. Monitoring changes of histone PTMs could pave the way to understanding the molecular mechanisms associated with epigenetic regulation of cell proliferation. Previously, our lab established a novel middle-down workflow using porous graphitic carbon (PGC) as a stationary phase to analyze histone PTMs, which utilizes the same reversed-phase chromatography for gradient separation as canonical proteomics coupled with online mass spectrometry (MS). Here, we applied this novel workflow for high-throughput analysis of histone modifications of H3.1 and H3.2 during the cell cycle. Collectively, we identified 1133 uniquely modified canonical histone H3 N-terminal tails. Consistent with previous findings, histone H3 phosphorylation increased significantly during the mitosis (M) phase. Histone H3 variant-specific and cell-cycle-dependent expressions of PTMs were observed, underlining the need to not combine H3.1 and H3.2 together as H3. We confirmed previously known H3 PTM crosstalk (e.g., K9me-S10ph) and revealed new information in this area as well. https://www.selleckchem.com/products/a-1210477.html These findings imply that the combinatorial PTMs play a role in cell cycle control, and they may serve as markers for proliferation.Coal and coal gangue spontaneous combustion (CGSC) occurs globally, causing significant environmental pollution. However, its emissions are poorly quantified and are overlooked in global or regional air pollutant emission inventories in previous studies, resulting in the underestimation of its impacts on climate, environment, and public health. This study quantified the emissions of various air pollutants originating from CGSC in Wuhai, a city in China, investigated emission characteristics, and estimated the contribution of CGSC emissions to fine particulate matter (PM2.5) air pollution and related health impacts on a regional scale. The results revealed that the CGSC-related PM2.5 emissions were approximately 4643 t a-1 (95% confidence interval (95% CI) 721; 10447), accounting for 26.3% of the total PM2.5 emissions. Alkanes, alkenes, and aromatics accounted for 69.4, 17.9, and 2.9%, respectively, of the total emissions of volatile organic compounds (VOCs). Due to CGSC emissions, the ambient PM2.5 concentration in Wuhai increased by 5.7 μg m-3 on average, while the nitrate concentration decreased. The number of premature deaths caused by exposure to ambient PM2.5 associated with CGSC reached 381 (95% CI 290; 452) in Wuhai and surrounding cities in 2017. Urgent control strategies and engineering techniques are needed to mitigate CGSC to protect public health.The directional flexibility of proteins is an equilibrium molecular property which is accessible to both experiment and computation. Single molecule force spectroscopy (SMFS) experiments report effective directional spring constants to describe the collective anisotropic response of a protein structure to mechanical pulling forces applied along selected axes. On the other hand, computational methods have thus far employed either indirect force based nonequilibrium simulations or coarse-grained elastic network models (ENM) to predict protein directional spring constants. Here, we examine the ability of equilibrium atomistic Molecular Dynamics (MD) simulations to estimate the directional flexibility and mechanical anisotropy of proteins. MD-derived effective directional spring constants are found to correlate well with SMFS spring constants (ρ2 = 0.97-0.99; Adj R2 = 0.92-0.99) and unfolding forces (ρ2 = 0.85-0.97; Adj R2 = 0.63-0.91) for five different globular proteins. Specifically, the computed spring consta85 bond vectors in Ub, we propose and validate a new covariance-propagation scheme to extract spring constants from ENM normal modes. We also critically examine the ability of ENM to predict directional flexibility of proteins and suggest modifications to improve these intuitive and scalable descriptions.Major strides have been made in the development of materials and devices based around low-dimensional hybrid group 14 metal halide perovskites. Thus far, this work has mostly focused on compounds containing highly toxic Pb, with the analogous less toxic Sn materials being comparatively poorly evolved. In response, the study herein aims to (i) provide insight into the impact of templating cations upon the structure of n = 1 2D tin iodide perovskites (where n refers to the number of contiguous two-dimensional (2D) inorganic layers, i.e., not separated by organic cations) and (ii) examine their potential as light absorbers for photovoltaic (PV) cells. It was discovered through systematic tuning of organic dications that imidazolium rings are able to induce the formation of (110)-oriented materials, including examples of "3 × 3" corrugated Sn-I perovskites. This structural outcome is a consequence of a combination of supramolecular interactions of the two endocyclic N atoms of the imidazolium rings with the Sn-I ng lead iodide material, which demonstrates that 2D Sn-based materials have significant potential as less toxic alternatives to their Pb counterparts.Monophosphate, an essential component of nucleic acids, as well as cell membranes and signaling molecules, is often bound to metal cations. Despite the biological importance of monophosphate-containing cell-signaling or lipid molecules, their propensity to bind the two most abundant cellular dications, Mg2+ and Ca2+, in a particular mode (inner/outer shell, mono/bidentate) is not well understood. Whether they prefer binding to Mg2+ than to Ca2+ and if they can outcompete the carboxylates of excitatory Asp/Glu and inhibitory gamma-aminobutyric acid (GABA) neurotransmitters in binding to Mg2+/Ca2+ remain unclear. To address these questions, we modeled cyclic adenosine/guanosine monophosphate (cAMP/cGMP), nucleoside 2',3'-cyclic phosphate, phosphatidylinositol (PI), phosphatidylserine (PS), and phosphatidylethanolamine (PEA) and determined their most stable metal-binding modes, including those of Asp/Glu and GABA, as well as their selectivity for Mg2+/Ca2+ using density functional theory combined with the polarizable continuum model.
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  • Temporary transfers of firearms from suicidal persons is a strategy to reduce the incidence of suicide deaths. We discuss a barrier to the effective operation of voluntary temporary firearm transfer laws the dearth of guidance on the liability for returning firearms to persons who voluntarily surrender them. We examine the laws of all 50 US states that regulate temporary surrenders of firearms and evaluate whether any provisions govern liability for returning temporarily surrendered firearms.Although 14 states create background check exceptions to permit temporary transfers of firearms from an owner to family, friends, retailers, or law enforcement, no states prescribe procedures for returning those firearms.ability for returning the firearms to people who voluntarily surrendered them.We recommend amending state laws to clarify the process and liability for returning temporarily surrendered firearms to the original owner. Such amendments would be intended to mitigate the potential chilling effect that lack of clarity and presumption of liability may impose on efficiently reducing firearm access to protect firearm owners at risk for suicide. (Am J Public Health. Published online ahead of print March 19, 2020 e1-e4. doi10.2105/AJPH.2019.305545).From April 2016 to June 2017, the Health + Housing Project employed four community health workers who engaged residents of two subsidized housing buildings in New York City to address individuals' broadly defined health needs, including social and economic risk factors. Following the intervention, we observed significant improvements in residents' food security, ability to pay rent, and connection to primary care. No immediate change was seen in acute health care use or more narrowly defined health outcomes. (Am J Public Health. Published online ahead of print March 19, 2020 e1-e4. doi10.2105/AJPH.2019.305544).The objective of the Los Angeles County, California (LAC), health care personnel (HCP) influenza vaccination improvement intervention was to increase HCP influenza vaccination coverage during the 2016-2017 influenza season via targeted outreach to LAC acute care hospitals. We selected 13 facilities for intervention and received tailored recommendations from a menu of evidence-based practices. Following the season, each hospital in the intervention group experienced a significant increase in vaccination coverage, which increased the LAC countywide average for all hospitals by 5%, from 74% to 79%. (Am J Public Health. Published online ahead of print March 19, 2020 e1-e3. doi10.2105/AJPH.2019.305555).Objectives. To investigate potential changes in burdens from coal-fired electricity-generating units (EGUcfs) that emit fine particulate matter (PM2.5, defined as matter with a nominal mean aerodynamic diameter of ≤ 2.5 µm) among racial/ethnic and economic groups after reduction of operations in 92 US EGUcfs.Methods. PM2.5 burdens calculated for EGUs listed in the 2008, 2011, and 2014 National Emissions Inventory were recalculated for 2017 after omitting emissions from 92 EGUcfs. The combined influence of race/ethnicity and poverty on burden estimates was characterized.Results. Omission of 92 EGUcfs decreased PM2.5 burdens attributable to EGUs by 8.6% for the entire population and to varying degrees for every population subgroup. Although the burden decreased across all subgroups, the decline was not equitable. After omission of the 92 EGUcfs, burdens were highest for the below-poverty and non-White subgroups. Proportional disparities between White and non-White subgroups increased. In our combined analysis, the burden was highest for the non-White-high-poverty subgroup.Conclusions. Our results indicate that subgroups living in poverty experience the greatest absolute burdens from EGUcfs. Changes as a result of EGUcf closures suggest a shift in burden from White to non-White subgroups. Policymakers could use burden analyses to jointly promote equity and reduce emissions. (Am J Public Health. Published online ahead of print March 19, 2020 e1-e7. doi10.2105/AJPH.2019.305558).Objectives. To determine the effect of new therapies and trends toward reduced mortality rates of melanoma.Methods. We reviewed melanoma incidence and mortality among Whites (the group most affected by melanoma) in 9 US Surveillance, Epidemiology, and End Results registry areas that recorded data between 1986 and 2016.Results. From 1986 to 2013, overall mortality rates increased by 7.5%. Beginning in 2011, the US Food and Drug Administration approved 10 new treatments for metastatic melanoma. From 2013 to 2016, overall mortality decreased by 17.9% (annual percent change [APC] = -6.2%; 95% confidence interval [CI] = -8.7%, -3.7%) with sharp declines among men aged 50 years or older (APC = -8.3%; 95% CI = -12.2%, -4.1%) starting in 2014. This recent, multiyear decline is the largest and most sustained improvement in melanoma mortality ever observed and is unprecedented in cancer medicine.Conclusions. The introduction of new therapies for metastatic melanoma was associated with a significant reduction in population-level mortality. Future research should focus on developing even more effective treatments, identifying biomarkers to select patients most likely to benefit, and renewing emphasis on public health approaches to reduce the number of patients with advanced disease. (Am J Public Health. Published online ahead of print March 19, 2020 e1-e3. doi10.2105/AJPH.2020.305567).Objectives. To examine the impact of extreme heat on emergency services in Boston, MA.Methods. We conducted relative risk and time series analyses of 911 dispatches of the Boston Police Department (BPD), Boston Emergency Medical Services (BEMS), and Boston Fire Department (BFD) from November 2010 to April 2014 to assess the impact of extreme heat on emergency services.Results. During the warm season, there were 2% (95% confidence interval [CI] = 0%, 5%) more BPD dispatches, 9% (95% CI = 7%, 12%) more BEMS dispatches, and 10% (95% CI = 5%, 15%) more BFD dispatches on days when the maximum temperature was 90°F or higher, which remained consistent when we considered multiple days of heat. A 10°F increase in daily maximum temperature, from 80° to 90°F, resulted in 1.016, 1.017, and 1.002 times the expected number of daily BPD, BEMS, and BFD dispatch calls, on average, after adjustment for other predictors.Conclusions. https://www.selleckchem.com/products/bay-218.html The burden of extreme heat on local emergency medical and police services may be agency-wide, and impacts on fire departments have not been previously documented.
    Temporary transfers of firearms from suicidal persons is a strategy to reduce the incidence of suicide deaths. We discuss a barrier to the effective operation of voluntary temporary firearm transfer laws the dearth of guidance on the liability for returning firearms to persons who voluntarily surrender them. We examine the laws of all 50 US states that regulate temporary surrenders of firearms and evaluate whether any provisions govern liability for returning temporarily surrendered firearms.Although 14 states create background check exceptions to permit temporary transfers of firearms from an owner to family, friends, retailers, or law enforcement, no states prescribe procedures for returning those firearms.ability for returning the firearms to people who voluntarily surrendered them.We recommend amending state laws to clarify the process and liability for returning temporarily surrendered firearms to the original owner. Such amendments would be intended to mitigate the potential chilling effect that lack of clarity and presumption of liability may impose on efficiently reducing firearm access to protect firearm owners at risk for suicide. (Am J Public Health. Published online ahead of print March 19, 2020 e1-e4. doi10.2105/AJPH.2019.305545).From April 2016 to June 2017, the Health + Housing Project employed four community health workers who engaged residents of two subsidized housing buildings in New York City to address individuals' broadly defined health needs, including social and economic risk factors. Following the intervention, we observed significant improvements in residents' food security, ability to pay rent, and connection to primary care. No immediate change was seen in acute health care use or more narrowly defined health outcomes. (Am J Public Health. Published online ahead of print March 19, 2020 e1-e4. doi10.2105/AJPH.2019.305544).The objective of the Los Angeles County, California (LAC), health care personnel (HCP) influenza vaccination improvement intervention was to increase HCP influenza vaccination coverage during the 2016-2017 influenza season via targeted outreach to LAC acute care hospitals. We selected 13 facilities for intervention and received tailored recommendations from a menu of evidence-based practices. Following the season, each hospital in the intervention group experienced a significant increase in vaccination coverage, which increased the LAC countywide average for all hospitals by 5%, from 74% to 79%. (Am J Public Health. Published online ahead of print March 19, 2020 e1-e3. doi10.2105/AJPH.2019.305555).Objectives. To investigate potential changes in burdens from coal-fired electricity-generating units (EGUcfs) that emit fine particulate matter (PM2.5, defined as matter with a nominal mean aerodynamic diameter of ≤ 2.5 µm) among racial/ethnic and economic groups after reduction of operations in 92 US EGUcfs.Methods. PM2.5 burdens calculated for EGUs listed in the 2008, 2011, and 2014 National Emissions Inventory were recalculated for 2017 after omitting emissions from 92 EGUcfs. The combined influence of race/ethnicity and poverty on burden estimates was characterized.Results. Omission of 92 EGUcfs decreased PM2.5 burdens attributable to EGUs by 8.6% for the entire population and to varying degrees for every population subgroup. Although the burden decreased across all subgroups, the decline was not equitable. After omission of the 92 EGUcfs, burdens were highest for the below-poverty and non-White subgroups. Proportional disparities between White and non-White subgroups increased. In our combined analysis, the burden was highest for the non-White-high-poverty subgroup.Conclusions. Our results indicate that subgroups living in poverty experience the greatest absolute burdens from EGUcfs. Changes as a result of EGUcf closures suggest a shift in burden from White to non-White subgroups. Policymakers could use burden analyses to jointly promote equity and reduce emissions. (Am J Public Health. Published online ahead of print March 19, 2020 e1-e7. doi10.2105/AJPH.2019.305558).Objectives. To determine the effect of new therapies and trends toward reduced mortality rates of melanoma.Methods. We reviewed melanoma incidence and mortality among Whites (the group most affected by melanoma) in 9 US Surveillance, Epidemiology, and End Results registry areas that recorded data between 1986 and 2016.Results. From 1986 to 2013, overall mortality rates increased by 7.5%. Beginning in 2011, the US Food and Drug Administration approved 10 new treatments for metastatic melanoma. From 2013 to 2016, overall mortality decreased by 17.9% (annual percent change [APC] = -6.2%; 95% confidence interval [CI] = -8.7%, -3.7%) with sharp declines among men aged 50 years or older (APC = -8.3%; 95% CI = -12.2%, -4.1%) starting in 2014. This recent, multiyear decline is the largest and most sustained improvement in melanoma mortality ever observed and is unprecedented in cancer medicine.Conclusions. The introduction of new therapies for metastatic melanoma was associated with a significant reduction in population-level mortality. Future research should focus on developing even more effective treatments, identifying biomarkers to select patients most likely to benefit, and renewing emphasis on public health approaches to reduce the number of patients with advanced disease. (Am J Public Health. Published online ahead of print March 19, 2020 e1-e3. doi10.2105/AJPH.2020.305567).Objectives. To examine the impact of extreme heat on emergency services in Boston, MA.Methods. We conducted relative risk and time series analyses of 911 dispatches of the Boston Police Department (BPD), Boston Emergency Medical Services (BEMS), and Boston Fire Department (BFD) from November 2010 to April 2014 to assess the impact of extreme heat on emergency services.Results. During the warm season, there were 2% (95% confidence interval [CI] = 0%, 5%) more BPD dispatches, 9% (95% CI = 7%, 12%) more BEMS dispatches, and 10% (95% CI = 5%, 15%) more BFD dispatches on days when the maximum temperature was 90°F or higher, which remained consistent when we considered multiple days of heat. A 10°F increase in daily maximum temperature, from 80° to 90°F, resulted in 1.016, 1.017, and 1.002 times the expected number of daily BPD, BEMS, and BFD dispatch calls, on average, after adjustment for other predictors.Conclusions. https://www.selleckchem.com/products/bay-218.html The burden of extreme heat on local emergency medical and police services may be agency-wide, and impacts on fire departments have not been previously documented.
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  • By age 15, adolescents reported more aggression than their parents. Parental hostility, family status, and adolescent gender predicted change in informant discrepancies. Practical and developmental implications are discussed for assessing and determining accurate change in adolescent aggressive behavior problems.Because the demographic composition of neighborhoods and schools overlaps, their effects on educational attainment are not independent of each other. Throughout the early teenage years, the timing and duration of exposure to neighborhood and school contexts can vary, advocating for a longitudinal approach when studying schooling outcomes. This study uses Avon Longitudinal Study of Parents and Children data (N = 4502; 49% female) to examine how exposure to poverty between ages 10-16 predicts educational attainment. The results indicate that enduring exposure to neighborhood poverty relates to educational attainment, while timing does not. For school poverty, longer exposure is related to lower attainment, but earlier exposure has a stronger impact than later exposure. Adolescents who were exposed to poverty in both contexts for the full observation period had the lowest educational attainment. The findings highlight the importance of understanding when and how long adolescents are exposed to contextual poverty.Heat shock proteins, in particular Hsp70, play a central role in proteostasis in eukaryotic cells. Due to its chaperone properties, Hsp70 is involved in various processes after stress and under normal physiological conditions. In contrast to mammals and many Diptera species, inducible members of the Hsp70 family in Drosophila are constitutively synthesized at a low level and undergo dramatic induction after temperature elevation or other forms of stress. In the courtship suppression paradigm used in this study, Drosophila males that have been repeatedly rejected by mated females during courtship are less likely than naive males to court other females. Although numerous genes with known function were identified to play important roles in long-term memory, there is, to the best of our knowledge, no direct evidence implicating Hsp70 in this process. To elucidate a possible role of Hsp70 in memory formation, we used D. melanogaster strains containing different hsp70 copy numbers, including strains carrying a deletion of all six hsp70 genes. Our investigations exploring the memory of courtship rejection paradigm demonstrated that a low constitutive level of Hsp70 is apparently required for learning and the formation of short and long-term memories in males. The performed transcriptomic studies demonstrate that males with different hsp70 copy numbers differ significantly in the expression of a few definite groups of genes involved in mating, reproduction, and immunity in response to rejection. Specifically, our analysis reveals several major pathways that depend on the presence of hsp70 in the genome and participate in memory formation and consolidation, including the cAMP signaling cascade.
    Patients taking low-dose aspirin to prevent cardiovascular disease (CVD) may also benefit from a reduced risk of colorectal cancer (CRC).

    The aim was to examine the preferences of people eligible for preventive treatment with low-dose aspirin and the trade-offs they are willing to make between CVD prevention, CRC prevention, and treatment risks.

    A cross-sectional study using a discrete choice experiment (DCE) survey was conducted in Italy in 2019 to elicit preferences for three benefit attributes (prevention of ischemic stroke, myocardial infarction, and CRC) and four risk attributes (intracranial and gastrointestinal bleeding, peptic ulcer, and severe allergic reaction) associated with use of low-dose aspirin. Latent class logit models were used to evaluate variation in treatment preferences.

    The DCE survey was completed by 1005 participants eligible for use of low-dose aspirin. A four-class model had the best fit for the primary CVD prevention group (n = 491), and a three-class model had the best fit for the secondary CVD prevention group (n = 514). For the primary CVD prevention group, where classes differed on age, education level, type 2 diabetes, exercise, and low-dose aspirin use, the most important attributes were intracranial bleeding (two classes), myocardial infarction (one class), and CRC (one class). For the secondary CVD prevention group, where classes differed on various comorbidities, self-reported health, exercise, and CVD medication use, the most important attributes were intracranial bleeding (two classes), myocardial infarction (one class), and gastrointestinal bleeding (one class).

    Patient preferences for the benefits and risks of low-dose aspirin differ significantly among people eligible for treatment as primary or secondary CVD prevention.
    Patient preferences for the benefits and risks of low-dose aspirin differ significantly among people eligible for treatment as primary or secondary CVD prevention.Patients critically ill with COVID-19 are at risk for thrombotic events despite prophylactic anticoagulation. Impaired fibrinolysis has been proposed as an underlying mechanism. https://www.selleckchem.com/products/azd1390.html Our objective was to determine if fibrinolysis stimulated by tissue plasminogen activator (tPA) differed between COVID patients and controls. Plasma from 14 COVID patients on prophylactic heparin therapy was obtained and compared with heparinized plasma from 14 different healthy donors to act as controls. Kaolin activated thromboelastography with heparinase was utilized to obtain baseline measurements and then repeated with the addition of 4 nM tPA. Baseline fibrinogen levels were higher in COVID plasma as measured by maximum clot amplitude (43.6 ± 6.9 mm vs. 23.2 ± 5.5 mm, p  less then  0.0001) and Clauss assay (595 ± 135 mg/dL vs. 278 ± 44 mg/dL, p  less then  0.0001). With the addition of tPA, fibrinolysis at 30 min after MA (LY30%) was lower (37.9 ± 16.5% vs. 58.9 ± 18.3%, p = 0.0035) and time to 50% lysis was longer (48.8 ± 16.3 vs. 30.5 ± 15.4 min, p = 0.0053) in the COVID-19 samples. Clotting times and rate of fibrin polymerization ('R' or 'α' parameters) were largely the same in both groups. Clot from COVID patients contains a higher fibrin content compared to standard controls and shows resistance to fibrinolysis induced by tPA. These findings suggest the clinical efficacy of thrombolytics may be reduced in COVID-19 patients.
    By age 15, adolescents reported more aggression than their parents. Parental hostility, family status, and adolescent gender predicted change in informant discrepancies. Practical and developmental implications are discussed for assessing and determining accurate change in adolescent aggressive behavior problems.Because the demographic composition of neighborhoods and schools overlaps, their effects on educational attainment are not independent of each other. Throughout the early teenage years, the timing and duration of exposure to neighborhood and school contexts can vary, advocating for a longitudinal approach when studying schooling outcomes. This study uses Avon Longitudinal Study of Parents and Children data (N = 4502; 49% female) to examine how exposure to poverty between ages 10-16 predicts educational attainment. The results indicate that enduring exposure to neighborhood poverty relates to educational attainment, while timing does not. For school poverty, longer exposure is related to lower attainment, but earlier exposure has a stronger impact than later exposure. Adolescents who were exposed to poverty in both contexts for the full observation period had the lowest educational attainment. The findings highlight the importance of understanding when and how long adolescents are exposed to contextual poverty.Heat shock proteins, in particular Hsp70, play a central role in proteostasis in eukaryotic cells. Due to its chaperone properties, Hsp70 is involved in various processes after stress and under normal physiological conditions. In contrast to mammals and many Diptera species, inducible members of the Hsp70 family in Drosophila are constitutively synthesized at a low level and undergo dramatic induction after temperature elevation or other forms of stress. In the courtship suppression paradigm used in this study, Drosophila males that have been repeatedly rejected by mated females during courtship are less likely than naive males to court other females. Although numerous genes with known function were identified to play important roles in long-term memory, there is, to the best of our knowledge, no direct evidence implicating Hsp70 in this process. To elucidate a possible role of Hsp70 in memory formation, we used D. melanogaster strains containing different hsp70 copy numbers, including strains carrying a deletion of all six hsp70 genes. Our investigations exploring the memory of courtship rejection paradigm demonstrated that a low constitutive level of Hsp70 is apparently required for learning and the formation of short and long-term memories in males. The performed transcriptomic studies demonstrate that males with different hsp70 copy numbers differ significantly in the expression of a few definite groups of genes involved in mating, reproduction, and immunity in response to rejection. Specifically, our analysis reveals several major pathways that depend on the presence of hsp70 in the genome and participate in memory formation and consolidation, including the cAMP signaling cascade. Patients taking low-dose aspirin to prevent cardiovascular disease (CVD) may also benefit from a reduced risk of colorectal cancer (CRC). The aim was to examine the preferences of people eligible for preventive treatment with low-dose aspirin and the trade-offs they are willing to make between CVD prevention, CRC prevention, and treatment risks. A cross-sectional study using a discrete choice experiment (DCE) survey was conducted in Italy in 2019 to elicit preferences for three benefit attributes (prevention of ischemic stroke, myocardial infarction, and CRC) and four risk attributes (intracranial and gastrointestinal bleeding, peptic ulcer, and severe allergic reaction) associated with use of low-dose aspirin. Latent class logit models were used to evaluate variation in treatment preferences. The DCE survey was completed by 1005 participants eligible for use of low-dose aspirin. A four-class model had the best fit for the primary CVD prevention group (n = 491), and a three-class model had the best fit for the secondary CVD prevention group (n = 514). For the primary CVD prevention group, where classes differed on age, education level, type 2 diabetes, exercise, and low-dose aspirin use, the most important attributes were intracranial bleeding (two classes), myocardial infarction (one class), and CRC (one class). For the secondary CVD prevention group, where classes differed on various comorbidities, self-reported health, exercise, and CVD medication use, the most important attributes were intracranial bleeding (two classes), myocardial infarction (one class), and gastrointestinal bleeding (one class). Patient preferences for the benefits and risks of low-dose aspirin differ significantly among people eligible for treatment as primary or secondary CVD prevention. Patient preferences for the benefits and risks of low-dose aspirin differ significantly among people eligible for treatment as primary or secondary CVD prevention.Patients critically ill with COVID-19 are at risk for thrombotic events despite prophylactic anticoagulation. Impaired fibrinolysis has been proposed as an underlying mechanism. https://www.selleckchem.com/products/azd1390.html Our objective was to determine if fibrinolysis stimulated by tissue plasminogen activator (tPA) differed between COVID patients and controls. Plasma from 14 COVID patients on prophylactic heparin therapy was obtained and compared with heparinized plasma from 14 different healthy donors to act as controls. Kaolin activated thromboelastography with heparinase was utilized to obtain baseline measurements and then repeated with the addition of 4 nM tPA. Baseline fibrinogen levels were higher in COVID plasma as measured by maximum clot amplitude (43.6 ± 6.9 mm vs. 23.2 ± 5.5 mm, p  less then  0.0001) and Clauss assay (595 ± 135 mg/dL vs. 278 ± 44 mg/dL, p  less then  0.0001). With the addition of tPA, fibrinolysis at 30 min after MA (LY30%) was lower (37.9 ± 16.5% vs. 58.9 ± 18.3%, p = 0.0035) and time to 50% lysis was longer (48.8 ± 16.3 vs. 30.5 ± 15.4 min, p = 0.0053) in the COVID-19 samples. Clotting times and rate of fibrin polymerization ('R' or 'α' parameters) were largely the same in both groups. Clot from COVID patients contains a higher fibrin content compared to standard controls and shows resistance to fibrinolysis induced by tPA. These findings suggest the clinical efficacy of thrombolytics may be reduced in COVID-19 patients.
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  • Thoracic and cardiovascular surgery requires learning both theoretical knowledge and technical skills. In this surgical field, several disparities exist between the different training programs around the world. This report describes the implementation of a portfolio in the teaching and assessment of French trainees in Thoracic and Cardiovascular surgery, following an electronic logbook model, aiming to improve the training program. The French surgical course is a twelve semesters' curriculum divided in 3 parts, each part containing knowledge, technical skills and behaviors objectives to be validated, defined by the French College of Thoracic and Cardiovascular surgery. The competencies are marked in the logbook, following a declarative model where the surgical trainee fills every surgical procedure attended (all or part) if he/she has observed, partially or fully performed, or supervised another trainee. All the surgical procedures are linked to theoretical e-learning lessons and each e-learning lesson includes a self-evaluation. https://www.selleckchem.com/products/tqb-3804-egrf-in-7.html This constitutes a competency-based assessment model with milestones both for surgeon trainees and their mentors. This portfolio also contains complementary tools such as an automated publication point calculation, a formatted curriculum vitae generator, and several contact tools between trainees. Implementation of a dedicated portfolio following an electronic logbook model appears to be a relevant pedagogic tool and survey element in the thoracic and cardiovascular surgery training program. Its use may lead to potential educational benefits for the trainee, reliable competency assessment for the supervising surgeon and for scientific society or national college.The surgical setting is a highly complex environment where, in ideal conditions, everything should be under control to ensure a positive outcome. However, the existing complexity opens the possibility for multiple failures along the process and many of those failures are related to what is call the non-technical skills of the members of the team. We cannot eradicate human error, but we can try to avoid future mistakes in our daily practice introducing the awareness for providing a high-quality care in which patient safety is crucial. This paper presents an easy approach to concepts and teaching possibilities of those non-technical skills.Principles of surgical training have not changed, but methods of training are evolving very fast. Online tools are being adopted in both knowledge and skills training for surgical residents. As a result, to evaluate the outcome of these tools, online assessment is also developing. Knowledge resources are very diverse ranging from lectures, webinars, surgical videos to three-dimensional planning and printing. Skills resources include virtual reality simulators, remote skills training and interdisciplinary teamwork. Assessment of E-learning tools can be performed using online questions, task-based simulations, branching scenarios and online interviews/discussions. In thoracic surgery, video assisted thoracic surgery (VATS) lobectomy simulator has been developed and it appears to be an important tool for minimally invasive thoracic surgery education. Training programs incorporate e-Learning in their curriculum and online training and assessment will become an important part of thoracic surgical training as well.In 2005, the European Respiratory Society (ERS) launched a project to harmonise education and training and to address the heterogeneity of respiratory health training across Europe. Since then, various educational activities have been developed for different target audiences. This article will describe the overall methodology and the projects developed over the years, detailing their objectives and target audiences. Moving forward, ERS strives to provide a structure for the continuing professional development of respiratory physicians.Founded in 1958 the UEMS (Union Européenne des Médecins Spécialistes-European Union of Medical Specialists) has become the largest European Medical organization representing over 1.5 million specialists of 43 Specialties in 39 countries. The primary goal of UEMS is to defend the interests of Specialists in the broadest sense of the word. This includes promoting the highest quality of care, the highest standards of training, continuous professional development (CPD) and continuous medical education (CME). For the latter the European Accreditation Council for Continuous Medical Education (EACCME) is one of the main assets of UEMS. The UEMS Section of Thoracic Surgery was created in 2013 and has substantially contributed to the improvement of the identity of Thoracic Surgery as a specialty throughout Europe. Its main activities are focusing on harmonization of training and organization of the format of the UEMS Board in Thoracic Surgery as well as further molding of the specialty via an intense collaboration with all involved stakeholders over the specialty boundaries.Durable mechanical circulatory support (MCS) systems are established therapy option in patients with end-stage heart failure, with increasing importance during the last years due to donor organ shortage. Left ventricular assist devices (LVADs) are traditionally implanted through median sternotomy (MS). However, improvement in the pump designs during the last years led to evolvement of new surgical approaches that aim to reduce the invasiveness of the procedure. Numerous reports and studies have shown the viability and possible advantages of less-invasive approach compared to the sternotomy approach. The less invasive implant strategies for LVADs, while vague in definition, are characterized by minimizing surgical trauma and if possible, cardio-pulmonary bypass related complications. Usually it involves minimizing or completely avoiding sternal trauma, avoiding heart luxation while simultaneously leaving the major part of pericardium intact. There is no consensus between the centers regarding the ideal approach for LVAD implantation. Some centers, like our center, perform by default VAD implantation using less invasive approach in almost all patients and some centers use only sternotomy approach. The aim of this review article is to shed light on the currently available less invasive options of LVAD implantation, with particular focus on the centrifugal pumps, and their possible advantages compared to traditional sternotomy approach.
    Thoracic and cardiovascular surgery requires learning both theoretical knowledge and technical skills. In this surgical field, several disparities exist between the different training programs around the world. This report describes the implementation of a portfolio in the teaching and assessment of French trainees in Thoracic and Cardiovascular surgery, following an electronic logbook model, aiming to improve the training program. The French surgical course is a twelve semesters' curriculum divided in 3 parts, each part containing knowledge, technical skills and behaviors objectives to be validated, defined by the French College of Thoracic and Cardiovascular surgery. The competencies are marked in the logbook, following a declarative model where the surgical trainee fills every surgical procedure attended (all or part) if he/she has observed, partially or fully performed, or supervised another trainee. All the surgical procedures are linked to theoretical e-learning lessons and each e-learning lesson includes a self-evaluation. https://www.selleckchem.com/products/tqb-3804-egrf-in-7.html This constitutes a competency-based assessment model with milestones both for surgeon trainees and their mentors. This portfolio also contains complementary tools such as an automated publication point calculation, a formatted curriculum vitae generator, and several contact tools between trainees. Implementation of a dedicated portfolio following an electronic logbook model appears to be a relevant pedagogic tool and survey element in the thoracic and cardiovascular surgery training program. Its use may lead to potential educational benefits for the trainee, reliable competency assessment for the supervising surgeon and for scientific society or national college.The surgical setting is a highly complex environment where, in ideal conditions, everything should be under control to ensure a positive outcome. However, the existing complexity opens the possibility for multiple failures along the process and many of those failures are related to what is call the non-technical skills of the members of the team. We cannot eradicate human error, but we can try to avoid future mistakes in our daily practice introducing the awareness for providing a high-quality care in which patient safety is crucial. This paper presents an easy approach to concepts and teaching possibilities of those non-technical skills.Principles of surgical training have not changed, but methods of training are evolving very fast. Online tools are being adopted in both knowledge and skills training for surgical residents. As a result, to evaluate the outcome of these tools, online assessment is also developing. Knowledge resources are very diverse ranging from lectures, webinars, surgical videos to three-dimensional planning and printing. Skills resources include virtual reality simulators, remote skills training and interdisciplinary teamwork. Assessment of E-learning tools can be performed using online questions, task-based simulations, branching scenarios and online interviews/discussions. In thoracic surgery, video assisted thoracic surgery (VATS) lobectomy simulator has been developed and it appears to be an important tool for minimally invasive thoracic surgery education. Training programs incorporate e-Learning in their curriculum and online training and assessment will become an important part of thoracic surgical training as well.In 2005, the European Respiratory Society (ERS) launched a project to harmonise education and training and to address the heterogeneity of respiratory health training across Europe. Since then, various educational activities have been developed for different target audiences. This article will describe the overall methodology and the projects developed over the years, detailing their objectives and target audiences. Moving forward, ERS strives to provide a structure for the continuing professional development of respiratory physicians.Founded in 1958 the UEMS (Union Européenne des Médecins Spécialistes-European Union of Medical Specialists) has become the largest European Medical organization representing over 1.5 million specialists of 43 Specialties in 39 countries. The primary goal of UEMS is to defend the interests of Specialists in the broadest sense of the word. This includes promoting the highest quality of care, the highest standards of training, continuous professional development (CPD) and continuous medical education (CME). For the latter the European Accreditation Council for Continuous Medical Education (EACCME) is one of the main assets of UEMS. The UEMS Section of Thoracic Surgery was created in 2013 and has substantially contributed to the improvement of the identity of Thoracic Surgery as a specialty throughout Europe. Its main activities are focusing on harmonization of training and organization of the format of the UEMS Board in Thoracic Surgery as well as further molding of the specialty via an intense collaboration with all involved stakeholders over the specialty boundaries.Durable mechanical circulatory support (MCS) systems are established therapy option in patients with end-stage heart failure, with increasing importance during the last years due to donor organ shortage. Left ventricular assist devices (LVADs) are traditionally implanted through median sternotomy (MS). However, improvement in the pump designs during the last years led to evolvement of new surgical approaches that aim to reduce the invasiveness of the procedure. Numerous reports and studies have shown the viability and possible advantages of less-invasive approach compared to the sternotomy approach. The less invasive implant strategies for LVADs, while vague in definition, are characterized by minimizing surgical trauma and if possible, cardio-pulmonary bypass related complications. Usually it involves minimizing or completely avoiding sternal trauma, avoiding heart luxation while simultaneously leaving the major part of pericardium intact. There is no consensus between the centers regarding the ideal approach for LVAD implantation. Some centers, like our center, perform by default VAD implantation using less invasive approach in almost all patients and some centers use only sternotomy approach. The aim of this review article is to shed light on the currently available less invasive options of LVAD implantation, with particular focus on the centrifugal pumps, and their possible advantages compared to traditional sternotomy approach.
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  • In group E, enucleation was performed in 17 eyes. https://www.selleckchem.com/products/limertinib.html Global salvage was obtained in 0 out of 2 eyes in set I, 2 out of 3 eyes in set II, 3 out of 5 in set III, and in 1 out of 2 eyes in set IV. Conclusions IVC with adjuvant IAC, LT, CT and IViC has shown favorable results as a treatment method for group D and group E retinoblastoma.Primary open angle glaucoma (POAG) is a multifactorial optic neuropathy, which progresses in a chronic manner. Several etiological factors are involved, including genetic factors, race, age, IOP or vascular, systemic factors. IOP has an established role in the initiation and evolution of glaucoma, but its interactions with additional risk factors are complex. We propose the notion of the Glaucoma Etiological Area (GEA), as a representation of all the elements acting in collaboration in the physiopathology of each glaucoma case. When combined in different proportions, these elements may trigger the typical glaucomatous optic neuropathy (GON). We know that the statistical values of IOP are valid for normal eyes, but the glaucoma eye is not a normal eye. The notion of GEA can open a new perspective to interpret IOP values and to assess the true value of IOP control as a treatment for glaucoma. Applying the GEA theory allows us to tune the role of IOP. Additional factors, such as ocular properties (RGCL status, Come, PEX = Pseudoexfoliation syndrome, POAG - primary open-angle glaucoma, RGCL = retinal ganglion cell layer, VFL = visual field loss.ANCA+ associated vasculitis (AAV) is a group of rare diseases with potentially vision-threatening complications. Ocular and orbital complications of these diseases are caused by vasculitis of the small vessels of the eye or by granulomatous mass formation. ANCA (anti-neutrophil cytoplasmic antibodies) represent a key component of pathophysiological pathways as well as a diagnostic marker. Various manifestations are reported in literature, scleritis and episcleritis being the most common, followed by pseudotumor orbitae. In vision-threatening orbital or ocular disease, aggressive systemic treatment with a combination of high-dose glucocorticoids and either cyclophosphamide or rituximab is needed. Certain cases require locoregional surgical management to preserve ocular integrity or vision. Ocular involvement of AAV remains a challenge in clinical practice, requiring multi-specialty cooperation in order to ensure the best possible visual outcome. Abbreviations AAV = ANCA+ associated vasculitis, ANCA = anti-neutrophil cytoplasmic antibodies, GPA = granulomatosis with polyangiitis, EGPA = eosinophilic granulomatosis with polyangiitis, MPA = microscopic polyangiitis.Objective To investigate the recent pieces of evidence regarding the bacterial ocular surface contamination and its treatment in the prophylaxis of post-cataract surgery endophthalmitis. Methods We conducted a literature research on the topic of interest and selected the most relevant data. Results The studies reported a relatively high rate of positive conjunctival culture and the most frequently isolated organism was Coagulase negative Staphylococcus, which is also the most common etiological agent of the postoperative endophthalmitis. The bacterial ocular surface load is influenced by age, climate, associated diseases, topical and systemic medication. The use of povidone-iodine alone or in association with levofloxacin eyedrops as prophylactic method is effective in reducing the conjunctival bacterial contamination and consequently decreases the incidence of postoperative endophthalmitis. Conclusions Based on the current pieces of evidence, adequate treatment of the bacterial ocular surface contamination prior to cataract surgery seems to be effective in preventing endophthalmitis after cataract surgery. Abbreviations EU = European Union, Spp. = Species, HIV = Human Immunodeficiency Virus.Traditional Chinese medicine and Chinese herbs have a demonstrated value for disease therapy and sub-health improvement. Attempts in this area tend to develop new forms to make their applications more convenient and wider. Here, we propose a novel Chinese herb microneedle (CHMN) patch by integrating the herbal extracts, Premna microphylla and Centella asiatica, with microstructure of microneedle for wound healing. Such path is composed of sap extracted from the herbal leaves via traditional kneading method and solidified by plant ash derived from the brine induced process of tofu in a well-designed mold. Because the leaves of the Premna microphylla are rich in pectin and various amino acids, the CHMN could be imparted with medicinal efficacy of heat clearing, detoxicating, detumescence and hemostatic. Besides, with the excellent pharmaceutical activity of Asiatic acid extracted from Centella asiatica, the CHMN is potential in promoting relevant growth factor genes expression in fibroblasts and showing excellent performance in anti-oxidant, anti-inflammatory and anti-bacterial activity. Taking advantages of these pure herbal compositions, we have demonstrated that the derived CHMN was with dramatical achievement in anti-bacteria, inhibiting inflammatory, collagen deposition, angiogenesis and tissue reconstruction during the wound closure. These results indicate that the integration of traditional Chinese herbs with progressive technologies will facilitate the development and promotion of traditional Chinese medicine in modern society.Upon skin injury, re-epithelialization must be triggered promptly to restore the integrity and barrier function of the epidermis. However, this process is often delayed or interrupted in chronic wounds like diabetic foot ulcers. Considering that BG particles can activate multiple genes in various cells, herein, we hypothesized that bioactive glass (BG) might be able to modulate the barrier functional behaviors of keratinocytes. By measuring the transepithelial electrical resistance (TEER) and the paracellular tracer flux, we found the 58S-BG extracts substantially enhanced the barrier function of keratinocyte monolayers. The BG extracts might exert such effects by promoting the keratinocyte differentiation and the formation of tight junctions, as evidenced by the increased expression of critical differentiation markers (K10 and involucrin) and TJ protein claudin-1, as well as the altered subcellular location of four major TJ proteins (claudin-1, occludin, JAM-A, and ZO-1). Besides, the cell scratch assay showed that BG extracts induced the collective migration of keratinocytes, though they did not accelerate the migration rate compared to the control.
    In group E, enucleation was performed in 17 eyes. https://www.selleckchem.com/products/limertinib.html Global salvage was obtained in 0 out of 2 eyes in set I, 2 out of 3 eyes in set II, 3 out of 5 in set III, and in 1 out of 2 eyes in set IV. Conclusions IVC with adjuvant IAC, LT, CT and IViC has shown favorable results as a treatment method for group D and group E retinoblastoma.Primary open angle glaucoma (POAG) is a multifactorial optic neuropathy, which progresses in a chronic manner. Several etiological factors are involved, including genetic factors, race, age, IOP or vascular, systemic factors. IOP has an established role in the initiation and evolution of glaucoma, but its interactions with additional risk factors are complex. We propose the notion of the Glaucoma Etiological Area (GEA), as a representation of all the elements acting in collaboration in the physiopathology of each glaucoma case. When combined in different proportions, these elements may trigger the typical glaucomatous optic neuropathy (GON). We know that the statistical values of IOP are valid for normal eyes, but the glaucoma eye is not a normal eye. The notion of GEA can open a new perspective to interpret IOP values and to assess the true value of IOP control as a treatment for glaucoma. Applying the GEA theory allows us to tune the role of IOP. Additional factors, such as ocular properties (RGCL status, Come, PEX = Pseudoexfoliation syndrome, POAG - primary open-angle glaucoma, RGCL = retinal ganglion cell layer, VFL = visual field loss.ANCA+ associated vasculitis (AAV) is a group of rare diseases with potentially vision-threatening complications. Ocular and orbital complications of these diseases are caused by vasculitis of the small vessels of the eye or by granulomatous mass formation. ANCA (anti-neutrophil cytoplasmic antibodies) represent a key component of pathophysiological pathways as well as a diagnostic marker. Various manifestations are reported in literature, scleritis and episcleritis being the most common, followed by pseudotumor orbitae. In vision-threatening orbital or ocular disease, aggressive systemic treatment with a combination of high-dose glucocorticoids and either cyclophosphamide or rituximab is needed. Certain cases require locoregional surgical management to preserve ocular integrity or vision. Ocular involvement of AAV remains a challenge in clinical practice, requiring multi-specialty cooperation in order to ensure the best possible visual outcome. Abbreviations AAV = ANCA+ associated vasculitis, ANCA = anti-neutrophil cytoplasmic antibodies, GPA = granulomatosis with polyangiitis, EGPA = eosinophilic granulomatosis with polyangiitis, MPA = microscopic polyangiitis.Objective To investigate the recent pieces of evidence regarding the bacterial ocular surface contamination and its treatment in the prophylaxis of post-cataract surgery endophthalmitis. Methods We conducted a literature research on the topic of interest and selected the most relevant data. Results The studies reported a relatively high rate of positive conjunctival culture and the most frequently isolated organism was Coagulase negative Staphylococcus, which is also the most common etiological agent of the postoperative endophthalmitis. The bacterial ocular surface load is influenced by age, climate, associated diseases, topical and systemic medication. The use of povidone-iodine alone or in association with levofloxacin eyedrops as prophylactic method is effective in reducing the conjunctival bacterial contamination and consequently decreases the incidence of postoperative endophthalmitis. Conclusions Based on the current pieces of evidence, adequate treatment of the bacterial ocular surface contamination prior to cataract surgery seems to be effective in preventing endophthalmitis after cataract surgery. Abbreviations EU = European Union, Spp. = Species, HIV = Human Immunodeficiency Virus.Traditional Chinese medicine and Chinese herbs have a demonstrated value for disease therapy and sub-health improvement. Attempts in this area tend to develop new forms to make their applications more convenient and wider. Here, we propose a novel Chinese herb microneedle (CHMN) patch by integrating the herbal extracts, Premna microphylla and Centella asiatica, with microstructure of microneedle for wound healing. Such path is composed of sap extracted from the herbal leaves via traditional kneading method and solidified by plant ash derived from the brine induced process of tofu in a well-designed mold. Because the leaves of the Premna microphylla are rich in pectin and various amino acids, the CHMN could be imparted with medicinal efficacy of heat clearing, detoxicating, detumescence and hemostatic. Besides, with the excellent pharmaceutical activity of Asiatic acid extracted from Centella asiatica, the CHMN is potential in promoting relevant growth factor genes expression in fibroblasts and showing excellent performance in anti-oxidant, anti-inflammatory and anti-bacterial activity. Taking advantages of these pure herbal compositions, we have demonstrated that the derived CHMN was with dramatical achievement in anti-bacteria, inhibiting inflammatory, collagen deposition, angiogenesis and tissue reconstruction during the wound closure. These results indicate that the integration of traditional Chinese herbs with progressive technologies will facilitate the development and promotion of traditional Chinese medicine in modern society.Upon skin injury, re-epithelialization must be triggered promptly to restore the integrity and barrier function of the epidermis. However, this process is often delayed or interrupted in chronic wounds like diabetic foot ulcers. Considering that BG particles can activate multiple genes in various cells, herein, we hypothesized that bioactive glass (BG) might be able to modulate the barrier functional behaviors of keratinocytes. By measuring the transepithelial electrical resistance (TEER) and the paracellular tracer flux, we found the 58S-BG extracts substantially enhanced the barrier function of keratinocyte monolayers. The BG extracts might exert such effects by promoting the keratinocyte differentiation and the formation of tight junctions, as evidenced by the increased expression of critical differentiation markers (K10 and involucrin) and TJ protein claudin-1, as well as the altered subcellular location of four major TJ proteins (claudin-1, occludin, JAM-A, and ZO-1). Besides, the cell scratch assay showed that BG extracts induced the collective migration of keratinocytes, though they did not accelerate the migration rate compared to the control.
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  • 01). In the multivariate regression analysis of ACD, which included LT, AL, WTW, sex, Km, CCT, and age, there was a reasonable prediction with adjusted R
     = 0.641.

    Cataract patients with longer AL and wider WTW have deeper ACD. With increasing age and lens thickening ACD becomes shallower. Based on the standardized coefficients of ACD multivariate regression analysis from the study, LT is the main factor that affects ACD, and is followed by AL.
    Cataract patients with longer AL and wider WTW have deeper ACD. With increasing age and lens thickening ACD becomes shallower. Based on the standardized coefficients of ACD multivariate regression analysis from the study, LT is the main factor that affects ACD, and is followed by AL.
    Recently developed immunosuppressive drugs, especially TNF antagonists, may enhance the risk of granulomatous infections, including leprosy. We aimed to evaluate the leprosy detection rate in patients under immunosuppression due to rheumatological, dermatological and gastroenterological diseases.

    We performed a systematic review of the literature by searching the PubMed, EMBASE, LILACS, Web of Science and Scielo databases through 2018. No date or language restrictions were applied. We included all articles that reported the occurrence of leprosy in patients under medication-induced immunosuppression.

    The search strategy resulted in 15,103 articles; finally, 20 articles were included, with 4 reporting longitudinal designs. The detection rate of leprosy ranged from 0.13 to 116.18 per 100,000 patients/year in the USA and Brazil, respectively. In the meta-analysis, the detection rate of cases of leprosy per 100,000 immunosuppressed patients with rheumatic diseases was 84 (detection rate = 0.00084; 95% CI = 0.0000-0.00266; I
     = 0%, p = 0.55).

    Our analysis showed that leprosy was relatively frequently detected in medication-induced immunosuppressed patients suffering from rheumatological diseases, and further studies are needed. The lack of an active search for leprosy in the included articles precluded more precise conclusions.

    This review is registered in PROSPERO with the registry number CRD42018116275 .
    This review is registered in PROSPERO with the registry number CRD42018116275 .
    Postnatal care (PNC) is important for preventing morbidity and mortality in mothers and newborns. Even though its importance is highlighted, PNC received less attention than antenatal care. This study determines the level of PNC coverage and its determinants in Srilanka.

    This is a secondary analysis of the 2016 Demographic and Health Survey. Receiving full postnatal care (FPNC) was defined with a set of indicators to detect adequate care for mother and newborn. Demographic and socio-economic associated factors for receiving FPNC were identified using binary and multiple logistic regression. Variables that had marginal relationship with receiving FPNC which p-value less than or equal to 0.2 at binary analysis were selected and included in the multiple logistic regression models. We used manual backward stepwise regression to identify variables which had independent association with receiving FPNC on the basis of adjusted odds ratios (AOR), with 95% confidence interval (CI) and p-value less than 0.05. All ae associated with FPNC coverage. Strategies that aim to improve postnatal care should target improvement of non-health factors as well.
    Receiving FPNC in Srilanka is high. https://www.selleckchem.com/products/ganetespib-sta-9090.html However, inequity remains to be a challenge. Socio-demographic factors are associated with FPNC coverage. Strategies that aim to improve postnatal care should target improvement of non-health factors as well.
    To guide decision-making on immunisation programmes for ageing adults in Europe, one of the aims of the Vaccines and InfecTious diseases in the Ageing popuLation (IMI2-VITAL) project is to assess the burden of disease (BoD) of (potentially) vaccine-preventable diseases ((P)VPD). We aimed to identify the available data sources to calculate the BoD of (P)VPD in participating VITAL countries and to pinpoint data gaps. Based on epidemiological criteria and vaccine availability, we prioritized (P) VPD caused by Extra-intestinal pathogenic Escherichia coli (ExPEC), norovirus, respiratory syncytial virus, Staphylococcus aureus, and pneumococcal pneumonia.

    We conducted a survey on available data (e.g. incidence, mortality, disability-adjusted life years (DALY), quality-adjusted life years (QALY), sequelae, antimicrobial resistance (AMR), etc.) among national experts from European countries, and carried out five pathogen-specific literature reviews by searching MEDLINE for peer-reviewed publications published between 2009 and 2019.

    Morbidity and mortality data were generally available for all five diseases, while summary BoD estimates were mostly lacking. Available data were not always stratified by age and risk group, which is especially important when calculating BoD for ageing adults. AMR data were available in several countries for S. aureus and ExPEC.

    This study provides an exhaustive overview of the available data sources and data gaps for the estimation of BoD of five (P) VPD in ageing adults in the EU/EAA, which is useful to guide pathogen-specific BoD studies and contribute to calculation of (P)VPDs BoD.
    This study provides an exhaustive overview of the available data sources and data gaps for the estimation of BoD of five (P) VPD in ageing adults in the EU/EAA, which is useful to guide pathogen-specific BoD studies and contribute to calculation of (P)VPDs BoD.
    Autopsies regularly aim to clarify the cause of death; however, relatives may directly benefit from autopsy results in the setting of heritable traits ("mortui vivos docent").

    A case of a sudden unexpected cardiac death of a 5.5-months-old child is presented. Autopsy and thorough postmortem cardiac examinations revealed a massively enlarged heart with endomyocardial fibroelastosis. Postmortem molecular testing (molecular autopsy) revealed an unusual combination of two biparental MYBPC3 gene mutations likely to underlie the cardiac abnormalities. Thus, the molecular autoptic findings also had consequences for the relatives of the deceased child and impact on further family planning.

    The presented case highlights the need for clinical autopsies including cardiac examinations and postmortem molecular testing; it also paves the way for further cascade screening of family members for cardiac disease, if a distinct genetic disorder is suspected.
    The presented case highlights the need for clinical autopsies including cardiac examinations and postmortem molecular testing; it also paves the way for further cascade screening of family members for cardiac disease, if a distinct genetic disorder is suspected.
    01). In the multivariate regression analysis of ACD, which included LT, AL, WTW, sex, Km, CCT, and age, there was a reasonable prediction with adjusted R  = 0.641. Cataract patients with longer AL and wider WTW have deeper ACD. With increasing age and lens thickening ACD becomes shallower. Based on the standardized coefficients of ACD multivariate regression analysis from the study, LT is the main factor that affects ACD, and is followed by AL. Cataract patients with longer AL and wider WTW have deeper ACD. With increasing age and lens thickening ACD becomes shallower. Based on the standardized coefficients of ACD multivariate regression analysis from the study, LT is the main factor that affects ACD, and is followed by AL. Recently developed immunosuppressive drugs, especially TNF antagonists, may enhance the risk of granulomatous infections, including leprosy. We aimed to evaluate the leprosy detection rate in patients under immunosuppression due to rheumatological, dermatological and gastroenterological diseases. We performed a systematic review of the literature by searching the PubMed, EMBASE, LILACS, Web of Science and Scielo databases through 2018. No date or language restrictions were applied. We included all articles that reported the occurrence of leprosy in patients under medication-induced immunosuppression. The search strategy resulted in 15,103 articles; finally, 20 articles were included, with 4 reporting longitudinal designs. The detection rate of leprosy ranged from 0.13 to 116.18 per 100,000 patients/year in the USA and Brazil, respectively. In the meta-analysis, the detection rate of cases of leprosy per 100,000 immunosuppressed patients with rheumatic diseases was 84 (detection rate = 0.00084; 95% CI = 0.0000-0.00266; I  = 0%, p = 0.55). Our analysis showed that leprosy was relatively frequently detected in medication-induced immunosuppressed patients suffering from rheumatological diseases, and further studies are needed. The lack of an active search for leprosy in the included articles precluded more precise conclusions. This review is registered in PROSPERO with the registry number CRD42018116275 . This review is registered in PROSPERO with the registry number CRD42018116275 . Postnatal care (PNC) is important for preventing morbidity and mortality in mothers and newborns. Even though its importance is highlighted, PNC received less attention than antenatal care. This study determines the level of PNC coverage and its determinants in Srilanka. This is a secondary analysis of the 2016 Demographic and Health Survey. Receiving full postnatal care (FPNC) was defined with a set of indicators to detect adequate care for mother and newborn. Demographic and socio-economic associated factors for receiving FPNC were identified using binary and multiple logistic regression. Variables that had marginal relationship with receiving FPNC which p-value less than or equal to 0.2 at binary analysis were selected and included in the multiple logistic regression models. We used manual backward stepwise regression to identify variables which had independent association with receiving FPNC on the basis of adjusted odds ratios (AOR), with 95% confidence interval (CI) and p-value less than 0.05. All ae associated with FPNC coverage. Strategies that aim to improve postnatal care should target improvement of non-health factors as well. Receiving FPNC in Srilanka is high. https://www.selleckchem.com/products/ganetespib-sta-9090.html However, inequity remains to be a challenge. Socio-demographic factors are associated with FPNC coverage. Strategies that aim to improve postnatal care should target improvement of non-health factors as well. To guide decision-making on immunisation programmes for ageing adults in Europe, one of the aims of the Vaccines and InfecTious diseases in the Ageing popuLation (IMI2-VITAL) project is to assess the burden of disease (BoD) of (potentially) vaccine-preventable diseases ((P)VPD). We aimed to identify the available data sources to calculate the BoD of (P)VPD in participating VITAL countries and to pinpoint data gaps. Based on epidemiological criteria and vaccine availability, we prioritized (P) VPD caused by Extra-intestinal pathogenic Escherichia coli (ExPEC), norovirus, respiratory syncytial virus, Staphylococcus aureus, and pneumococcal pneumonia. We conducted a survey on available data (e.g. incidence, mortality, disability-adjusted life years (DALY), quality-adjusted life years (QALY), sequelae, antimicrobial resistance (AMR), etc.) among national experts from European countries, and carried out five pathogen-specific literature reviews by searching MEDLINE for peer-reviewed publications published between 2009 and 2019. Morbidity and mortality data were generally available for all five diseases, while summary BoD estimates were mostly lacking. Available data were not always stratified by age and risk group, which is especially important when calculating BoD for ageing adults. AMR data were available in several countries for S. aureus and ExPEC. This study provides an exhaustive overview of the available data sources and data gaps for the estimation of BoD of five (P) VPD in ageing adults in the EU/EAA, which is useful to guide pathogen-specific BoD studies and contribute to calculation of (P)VPDs BoD. This study provides an exhaustive overview of the available data sources and data gaps for the estimation of BoD of five (P) VPD in ageing adults in the EU/EAA, which is useful to guide pathogen-specific BoD studies and contribute to calculation of (P)VPDs BoD. Autopsies regularly aim to clarify the cause of death; however, relatives may directly benefit from autopsy results in the setting of heritable traits ("mortui vivos docent"). A case of a sudden unexpected cardiac death of a 5.5-months-old child is presented. Autopsy and thorough postmortem cardiac examinations revealed a massively enlarged heart with endomyocardial fibroelastosis. Postmortem molecular testing (molecular autopsy) revealed an unusual combination of two biparental MYBPC3 gene mutations likely to underlie the cardiac abnormalities. Thus, the molecular autoptic findings also had consequences for the relatives of the deceased child and impact on further family planning. The presented case highlights the need for clinical autopsies including cardiac examinations and postmortem molecular testing; it also paves the way for further cascade screening of family members for cardiac disease, if a distinct genetic disorder is suspected. The presented case highlights the need for clinical autopsies including cardiac examinations and postmortem molecular testing; it also paves the way for further cascade screening of family members for cardiac disease, if a distinct genetic disorder is suspected.
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  • This study investigated whether 6 weeks of basketball combined with mathematics once a week in physical education lessons could improve children's motivation for mathematics. Seven hundred fifty-seven children (mean age = 10.4 years, age range 7-12 years) were randomly selected to have either basketball combined with mathematics once a week (BM) or to have basketball sessions without mathematics (CON). Children in BM and CON motivation for classroom-based mathematics were measured using the Academic Self-Regulation Questionnaire (SRQ-A) before (T0) and after the intervention (T1). Among the BM, levels of intrinsic motivation, feelings of competence, and autonomy were measured using the Post-Experimental Intrinsic Motivation Inventory (IMI) questionnaire acutely after a basketball session combined with mathematics and immediately after a session of classroom-based mathematics. https://www.selleckchem.com/products/cadd522.html BM had significantly higher acute levels of perceived autonomy (+14.24%, p less then 0.0001), competencies (+6.33%, p less then 0.0001), and intrinsic motivation (+16.09%, p less then 0.0001) during basketball sessions combined with mathematics compared to when having classroom-based mathematics. A significant decrease in the mean for intrinsic motivation was observed from T0 to T1 for CON (-9.38%, p less then 0.001), but not for BM (-0.39%, p = 0.98). BM had a more positive development in intrinsic motivation compared to CON from T0 to T1 (p = 0.006), meaning that BM had a positive influence on children's intrinsic motivation for classroom-based mathematics. This study indicates that basketball combined with mathematics is an intrinsically motivating way to practice mathematics, which also has a positive influence on children's general intrinsic motivation for mathematics in the classroom.Science museums aim to provide educational experiences for both children and adults. To achieve this goal, museum displays must convey scientifically-relevant relationships, such as the similarities that unite members of a natural category, and the connections between scientific models and observable objects and events. In this paper, we explore how research on comparison could be leveraged to support learning about such relationships. We describe how museum displays could promote educationally-relevant comparisons involving natural specimens and scientific models. We also discuss how these comparisons could be supported through the design of a display-in particular, by using similarity, space, and language to facilitate relational thinking for children and their adult companions. Such supports may be pivotal given the informal nature of learning in museums.This paper reports results from a longitudinal study on the impact of the lockdown on daily self-reported life satisfaction levels during the first wave of the COVID-19 pandemic in Spain. A stable panel (N = 1,131) of adult subjects were surveyed during 84 consecutive days (March 29-June 20, 2020). They were asked to report daily life satisfaction and health state levels. Interestingly, daily life satisfaction increased during the lockdown. At the beginning of the experiment, subjects were asked to guess the end-week of the lockdown, against a possible monetary reward for accurate forecasts. Subjects predicting a longer lockdown period reported a higher average level of daily life satisfaction. Females reported on average lower levels of daily life satisfaction, but exhibited a stronger tendency to report higher levels of life satisfaction, the longer their lockdown forecast. Individual heterogeneity in life satisfaction levels can be partly attributed to personality traits, with neuroticism having a negative effect, while extraversion and agreeableness having a positive effect on daily life satisfaction.A growing body of research highlights that adults with autism spectrum disorder (ASD) have poor health outcomes, yet effective health interventions are lacking for this population. While mobile health applications demonstrate potential for promoting physical activity (PA) in adults with ASD, scientific evidence for supporting this tool's long-term effectiveness on PA behavior change remains inconclusive. This study aimed to provide the latest information on PA research and the prospective role of mobile health applications for promoting PA in adults with ASD. A literature review demonstrated that a few available studies show contradictory results regarding PA levels in adults with ASD, and behavior change techniques and gamification-guided mobile health applications can be promising tactics to leverage autism's strengths and increase PA in these individuals. Optimizing design decisions based on needs analysis and user feedback is crucial to identifying and developing a sustainable mobile health intervention for PA promotion in adults with ASD.It is important to understand the processes behind how and why individuals emerge as leaders, so that the best and most capable individuals may occupy leadership positions. So far, most literature in this area has focused on individual characteristics, such as personality or cognitive ability. While interactions between individuals and context do get research attention, we still lack a comprehensive understanding of how the social context at work may help individuals to emerge as leaders. Such knowledge could make an important contribution toward getting the most capable, rather than the most dominant or narcissistic individuals, into leadership positions. In the present work, we contribute toward closing this gap by testing a mediation chain linking a leader's leader self-awareness to a follower's leadership emergence with two time-lagged studies (n study1 = 449, n study2 = 355). We found that the leader's leader self-awareness was positively related to (a) the follower's leadership emergence and (b) the follower's nomination for promotion and that both relationships were serially mediated by the follower's self-leadership and the follower's leader self-efficacy. We critically discuss our findings and provide ideas for future research.The coronavirus disease 2019 (COVID-19) pandemic has had profound effects on all aspects of society. Families were among those directly impacted by the first measures imposed by health authorities worldwide to contain the spread of the Sars-CoV-2 virus, where social distancing and mandatory quarantine were the main approaches implemented. Notably, little is yet known about how social distancing during COVID-19 has altered families' daily routines, particularly regarding music-related behaviors. The aim of this study was 2-fold (i) to explore changes in families' daily routine and caregivers' levels of well-being and stress during the COVID-19 outbreak in Brazil and (ii) to investigate whether musical behaviors of caregivers and the children under their care (aged from 3 to 6 years old) changed during social distancing. One hundred and eighty-eight caregivers residing in Brazil participated in an online cross-sectional study conducted between July and August 2020. Our findings suggest significant changes in families' dynamics during the COVID-19 outbreak, with parents (especially mothers) spending more time on childcare and a substantial decrease in caregiver's well-being.
    This study investigated whether 6 weeks of basketball combined with mathematics once a week in physical education lessons could improve children's motivation for mathematics. Seven hundred fifty-seven children (mean age = 10.4 years, age range 7-12 years) were randomly selected to have either basketball combined with mathematics once a week (BM) or to have basketball sessions without mathematics (CON). Children in BM and CON motivation for classroom-based mathematics were measured using the Academic Self-Regulation Questionnaire (SRQ-A) before (T0) and after the intervention (T1). Among the BM, levels of intrinsic motivation, feelings of competence, and autonomy were measured using the Post-Experimental Intrinsic Motivation Inventory (IMI) questionnaire acutely after a basketball session combined with mathematics and immediately after a session of classroom-based mathematics. https://www.selleckchem.com/products/cadd522.html BM had significantly higher acute levels of perceived autonomy (+14.24%, p less then 0.0001), competencies (+6.33%, p less then 0.0001), and intrinsic motivation (+16.09%, p less then 0.0001) during basketball sessions combined with mathematics compared to when having classroom-based mathematics. A significant decrease in the mean for intrinsic motivation was observed from T0 to T1 for CON (-9.38%, p less then 0.001), but not for BM (-0.39%, p = 0.98). BM had a more positive development in intrinsic motivation compared to CON from T0 to T1 (p = 0.006), meaning that BM had a positive influence on children's intrinsic motivation for classroom-based mathematics. This study indicates that basketball combined with mathematics is an intrinsically motivating way to practice mathematics, which also has a positive influence on children's general intrinsic motivation for mathematics in the classroom.Science museums aim to provide educational experiences for both children and adults. To achieve this goal, museum displays must convey scientifically-relevant relationships, such as the similarities that unite members of a natural category, and the connections between scientific models and observable objects and events. In this paper, we explore how research on comparison could be leveraged to support learning about such relationships. We describe how museum displays could promote educationally-relevant comparisons involving natural specimens and scientific models. We also discuss how these comparisons could be supported through the design of a display-in particular, by using similarity, space, and language to facilitate relational thinking for children and their adult companions. Such supports may be pivotal given the informal nature of learning in museums.This paper reports results from a longitudinal study on the impact of the lockdown on daily self-reported life satisfaction levels during the first wave of the COVID-19 pandemic in Spain. A stable panel (N = 1,131) of adult subjects were surveyed during 84 consecutive days (March 29-June 20, 2020). They were asked to report daily life satisfaction and health state levels. Interestingly, daily life satisfaction increased during the lockdown. At the beginning of the experiment, subjects were asked to guess the end-week of the lockdown, against a possible monetary reward for accurate forecasts. Subjects predicting a longer lockdown period reported a higher average level of daily life satisfaction. Females reported on average lower levels of daily life satisfaction, but exhibited a stronger tendency to report higher levels of life satisfaction, the longer their lockdown forecast. Individual heterogeneity in life satisfaction levels can be partly attributed to personality traits, with neuroticism having a negative effect, while extraversion and agreeableness having a positive effect on daily life satisfaction.A growing body of research highlights that adults with autism spectrum disorder (ASD) have poor health outcomes, yet effective health interventions are lacking for this population. While mobile health applications demonstrate potential for promoting physical activity (PA) in adults with ASD, scientific evidence for supporting this tool's long-term effectiveness on PA behavior change remains inconclusive. This study aimed to provide the latest information on PA research and the prospective role of mobile health applications for promoting PA in adults with ASD. A literature review demonstrated that a few available studies show contradictory results regarding PA levels in adults with ASD, and behavior change techniques and gamification-guided mobile health applications can be promising tactics to leverage autism's strengths and increase PA in these individuals. Optimizing design decisions based on needs analysis and user feedback is crucial to identifying and developing a sustainable mobile health intervention for PA promotion in adults with ASD.It is important to understand the processes behind how and why individuals emerge as leaders, so that the best and most capable individuals may occupy leadership positions. So far, most literature in this area has focused on individual characteristics, such as personality or cognitive ability. While interactions between individuals and context do get research attention, we still lack a comprehensive understanding of how the social context at work may help individuals to emerge as leaders. Such knowledge could make an important contribution toward getting the most capable, rather than the most dominant or narcissistic individuals, into leadership positions. In the present work, we contribute toward closing this gap by testing a mediation chain linking a leader's leader self-awareness to a follower's leadership emergence with two time-lagged studies (n study1 = 449, n study2 = 355). We found that the leader's leader self-awareness was positively related to (a) the follower's leadership emergence and (b) the follower's nomination for promotion and that both relationships were serially mediated by the follower's self-leadership and the follower's leader self-efficacy. We critically discuss our findings and provide ideas for future research.The coronavirus disease 2019 (COVID-19) pandemic has had profound effects on all aspects of society. Families were among those directly impacted by the first measures imposed by health authorities worldwide to contain the spread of the Sars-CoV-2 virus, where social distancing and mandatory quarantine were the main approaches implemented. Notably, little is yet known about how social distancing during COVID-19 has altered families' daily routines, particularly regarding music-related behaviors. The aim of this study was 2-fold (i) to explore changes in families' daily routine and caregivers' levels of well-being and stress during the COVID-19 outbreak in Brazil and (ii) to investigate whether musical behaviors of caregivers and the children under their care (aged from 3 to 6 years old) changed during social distancing. One hundred and eighty-eight caregivers residing in Brazil participated in an online cross-sectional study conducted between July and August 2020. Our findings suggest significant changes in families' dynamics during the COVID-19 outbreak, with parents (especially mothers) spending more time on childcare and a substantial decrease in caregiver's well-being.
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