Comparing Telemedicine and In-Person Clinical Evaluations for Pediatric Urology Concerns.

INTRODUCTION: Telemedicine may promote equitable health care delivery, particularly in rural and underserved regions. While patient and provider satisfaction with telemedicine appear to be high, it remains unclear if telemedicine accomplishes the same clinical goals as in-person clinic visits. We undertook this study to compare the differences in history-taking, physical examination, and recommended follow-up in new pediatric urology patients seen via telemedicine and in-person. METHODS: This cross-sectional study was performed by retrospectively reviewing the charts of all new patients visiting the general pediatric urology clinic at a single freestanding children's hospital in January and April of three consecutive years (2019, 2020, 2021). Data were abstracted on patient demographics, comprehensiveness of history of present illness, completeness of physical examination, and recommended follow-up. Patients seen by telemedicine and in-person were compared. RESULTS: Of 1354 patients, 1244 (91.9%) had in-person and 110 (8.1%) telemedicine visits. Telemedicine patients had a median of 4 history of present illness components recorded; in-person patients had 3 (P < 0.0001). Patients seen in-person had a more comprehensive physical examination recorded compared with telemedicine patients (median 12 vs 2 systems, P < 0.0001). Significantly fewer telemedicine patients were discharged from clinic after the initial visit (2.7% vs 16.5%), and significantly more were asked to return for additional evaluation (39.1% vs 23.2, P < 0.0001). CONCLUSIONS: Initial pediatric urology telemedicine consultations gathered more historical and fewer physical examination components and were more likely to require an additional clinic visit for evaluation. Goals of care should be considered when selecting a visit modality.

Novel mutations of the PAX6, FOXC1, and PITX2 genes cause abnormal development of the iris in Vietnamese individuals.

Purpose: Congenital iris abnormality is a feature of several genetic conditions, such as aniridia syndrome and anterior segment degeneration (ASD) disorders. Aniridia syndrome is caused by mutations in the PAX6 gene or its regulatory elements in the locus 11p13 or deletions of contiguous genes, while ASDs are the result of mutations in various genes, such as PAX6, FOXC1, PITX2, and CYP1B1. This study aims to identify pathogenic mutations in Vietnamese individuals with congenital anomalies of the iris. Methods: Genomic DNA was extracted from peripheral blood of 24 patients belonging to 15 unrelated families and their available family members. Multiplex ligation-dependent probe amplification (MLPA) was used to detect the deletions or duplications in the 11p13-14 region, including the PAX6 gene and its neighboring genes. Direct PCR sequencing was used to screen mutations in 13 exons and flanking sequences of the PAX6 gene. The patients without mutation in the PAX6 locus were further analyzed with whole exome sequencing (WES). Identified mutations were tested with segregation analysis in proband family members. Results: We identified a total of 8 novel and 4 recurrent mutations in 20 of 24 affected individuals from 12 families. Among these mutations, one large deletion of the whole PAX6 gene and another deletion of the PAX6 downstream region containing the DCDC1 and ELP4 genes were identified. Eight mutations were detected in PAX6, including four nonsense, three frameshift, and one splice site. In addition, two point mutations were identified in the FOXC1 and PITX2 genes in patients without mutation in PAX6. Some of the mutations segregated in an autosomal dominant pattern where family members were available. Conclusions: This study provides new data on causative mutations in individuals with abnormal development of iris tissue in Vietnam. These results contribute to clinical management and genetic counseling for affected people and their families.

Stability of 40 cytokines/chemokines in chronically ill patients under different storage conditions.

Numerous studies point to the utility of blood cytokine measurements in the diagnosis and treatment of human disease. Advances in detection allow robust multiplex analysis. However, cytokines are present at low levels and are produced and act in complex networks which can remain active in stored blood. A major barrier to the routine use of cytokines as clinical biomarkers is sample management prior to analysis. Studies on cytokine stability under storage frequently use 'spiked' normal control plasma or serum to generate detectable levels of the cytokines of interest. These conditions may oversimplify the reality of clinically complex samples and provide limited information regarding optimal management of whole blood samples prior to plasma separation. Cytokine stability has also been addressed previously using plasma from normal individuals under different conditions of anticoagulant use, storage time and temperature of storage. No studies have as yet been undertaken to address cytokine stability in critically ill patients which may differ from normal, healthy individuals due to underlying cofounders such as inflammation. To address these issues, we subjected samples from five patients exhibiting an inflammatory disease state to three storage extremes which might be encountered in a clinical setting, prior to analysis of 40 cytokines. Blood drawn into EDTA or ACD anticoagulant was immediately separated and plasma stored at -80 °C. Matched samples were stored as follows; whole blood overnight at room temperature, or whole blood or plasma stored 10 days at 4 °C. We used equivalence testing to determine the similarity of stored cytokine values to baseline values. In ACD plasma, Eotaxin, IL-6, IL-11, IL-15, IP10, MDC, MCP-1 met equivalence to baseline in all storage conditions while for EDTA plasma stored 10 days at 4 °C EGF, FGF2, Fractalkine, G-CSF, IL-1ß, IL-5, IL-6, IL-7, IL-11, IP-10, TGFα and TNFα showed equivalence to baseline measurements. Intraclass Correlation Coefficients (ICC) were calculated and the following cytokines showed good to excellent agreement across all 4 storage conditions: Eotaxin, IL-5, IL-6, IL-11, IL-13, IP-10, MCP-1 and TNFα when collected in EDTA, and Eotaxin, IL-5, IL-6, IL-11, IL12-p40, IL-15, IP-10 and MCP-1 when collected in ACD. Five plasma cytokines were identified as being the least stable in both ACD and EDTA: IL-7, IL-9, IL12p70, RANTES, sCD40L, while IL-1ß was identified as unstable stored in ACD plasma. This study identified several clinically important cytokines that are remarkably stable in blood and plasma, and some that stored poorly. To our knowledge, this is the first cytokine storage study to use medically unwell patient samples and equivalence testing to evaluate the stability of measured cytokine values after storage.

Health Literacy, eHealth Literacy, Adherence to Infection Prevention and Control Procedures, Lifestyle Changes, and Suspected COVID-19 Symptoms Among Health Care Workers During Lockdown: Online Survey.

BACKGROUND: The COVID-19 pandemic has imposed a heavy burden on health care systems and governments. Health literacy (HL) and eHealth literacy (as measured by the eHealth Literacy Scale [eHEALS]) are recognized as strategic public health elements but they have been underestimated during the pandemic. HL, eHEALS score, practices, lifestyles, and the health status of health care workers (HCWs) play crucial roles in containing the COVID-19 pandemic. OBJECTIVE: The aim of this study is to evaluate the psychometric properties of the eHEALS and examine associations of HL and eHEALS scores with adherence to infection prevention and control (IPC) procedures, lifestyle changes, and suspected COVID-19 symptoms among HCWs during lockdown. METHODS: We conducted an online survey of 5209 HCWs from 15 hospitals and health centers across Vietnam from April 6 to April 19, 2020. Participants answered questions related to sociodemographics, HL, eHEALS, adherence to IPC procedures, behavior changes in eating, smoking, drinking, and physical activity, and suspected COVID-19 symptoms. Principal component analysis, correlation analysis, and bivariate and multivariate linear and logistic regression models were used to validate the eHEALS and examine associations. RESULTS: The eHEALS had a satisfactory construct validity with 8 items highly loaded on one component, with factor loadings ranked from 0.78 to 0.92 explaining 76.34% of variance; satisfactory criterion validity as correlated with HL (ρ=0.42); satisfactory convergent validity with high item-scale correlations (ρ=0.80-0.84); and high internal consistency (Cronbach α=.95). HL and eHEALS scores were significantly higher in men (unstandardized coefficient [B]=1.01, 95% CI 0.57-1.45, P<.001; B=0.72, 95% CI 0.43-1.00, P<.001), those with a better ability to pay for medication (B=1.65, 95% CI 1.25-2.05, P<.001; B=0.60, 95% CI 0.34-0.86, P<.001), doctors (B=1.29, 95% CI 0.73-1.84, P<.001; B 0.56, 95% CI 0.20-0.93, P=.003), and those with epidemic containment experience (B=1.96, 95% CI 1.56-2.37, P<.001; B=0.64, 95% CI 0.38-0.91, P<.001), as compared to their counterparts, respectively. HCWs with higher HL or eHEALS scores had better adherence to IPC procedures (B=0.13, 95% CI 0.10-0.15, P<.001; B=0.22, 95% CI 0.19-0.26, P<.001), had a higher likelihood of healthy eating (odds ratio [OR] 1.04, 95% CI 1.01-1.06, P=.001; OR 1.04, 95% CI 1.02-1.07, P=.002), were more physically active (OR 1.03, 95% CI 1.02-1.03, P<.001; OR 1.04, 95% CI 1.03-1.05, P<.001), and had a lower likelihood of suspected COVID-19 symptoms (OR 0.97, 95% CI 0.96-0.98, P<.001; OR 0.96, 95% CI 0.95-0.98, P<.001), respectively. CONCLUSIONS: The eHEALS is a valid and reliable survey tool. Gender, ability to pay for medication, profession, and epidemic containment experience were independent predictors of HL and eHEALS scores. HCWs with higher HL or eHEALS scores had better adherence to IPC procedures, healthier lifestyles, and a lower likelihood of suspected COVID-19 symptoms. Efforts to improve HCWs' HL and eHEALS scores can help to contain the COVID-19 pandemic and minimize its consequences.

Evaluation of the functional properties of cryopreserved buffy coat-derived monocytes for monocyte monolayer assay.

BACKGROUND: Monocyte monolayer assay (MMA) is a compatibility testing method for evaluating the clinical significance of red blood cell (RBC) alloantibodies. Time-consuming monocyte isolation procedures and requirement for fresh monocytes have limited application of the MMA. The aim of this study was to develop and assess the utility and efficacy of cryopreserved buffy coat (BC)-derived monocytes for MMA application. STUDY DESIGN AND METHODS: Peripheral blood mononuclear cells (PBMNCs) were isolated from BC or peripheral blood (PB) and pooled and BC PBMNCs were cryopreserved. Monocytes from pooled PBMNCs were incubated with anti-D-sensitized, anti-Scianna2 (Sc2)-sensitized, anti-AnWj-sensitized, or anti-Jra -sensitized RBCs or lipopolysaccharide (LPS). MMA phagocytic index (PI) and membrane integrity were determined microscopically, and cytokine release was measured by Luminex technology. RESULTS: PBMNC isolation rates from fresh BC and PB were not comparable (67.4 ± 6.3 and 75.8 ± 7.7% respectively, p = 0.024). There was no significant difference in PBMNC membrane integrity (fresh PB, 100%; fresh BC, 100%; cryopreserved BC, 95.2 ± 1.2%), postwash recovery (fresh PB, 85.9 ± 3.1; fresh BC, 86.9 ± 6.7; cryopreserved BC, 84.8 ± 5.1), or monocyte PI (fresh PB, 82 ± 10; fresh BC, 77 ± 11; cryopreserved BC = 80 ± 6). Monocytes from pooled cryopreserved BC PBMNCs reacted with RBCs sensitized with anti-D and RBC alloantibodies, including anti-Sc2, anti-Jra , and anti-AnWj. CONCLUSIONS: Monocytes from pooled cryopreserved BC PBMNCs can be used reliably to evaluate phagocytic responses of sensitized RBCs and to assess clinical significance of RBC alloantibodies.

Inositol-Triphosphate 3-Kinase C Mediates Inflammasome Activation and Treatment Response in Kawasaki Disease.

Kawasaki disease (KD) is a multisystem vasculitis that predominantly targets the coronary arteries in children. Phenotypic similarities between KD and recurrent fever syndromes point to the potential role of inflammasome activation in KD. Mutations in NLRP3 are associated with recurrent fever/autoinflammatory syndromes. We show that the KD-associated genetic polymorphism in inositol-triphosphate 3-kinase C (ITPKC) (rs28493229) has important functional consequences, governing ITPKC protein levels and thereby intracellular calcium, which in turn regulates NLRP3 expression and production of IL-1ß and IL-18. Analysis of transcript abundance, protein levels, and cellular response profiles from matched, serial biospecimens from a cohort of genotyped KD subjects points to the critical role of ITPKC in mediating NLRP3 inflammasome activation. Treatment failure in those with the high-risk ITPKC genotype was associated with the highest basal and stimulated intracellular calcium levels and with increased cellular production of IL-1ß and IL-18 and higher circulating levels of both cytokines. Mechanistic studies using Itpkc-deficient mice in a disease model support the genomic, cellular, and clinical findings in affected children. Our findings provide the mechanism behind the observed efficacy of rescue therapy with IL-1 blockade in recalcitrant KD, and we identify that regulation of calcium mobilization is fundamental to the underlying immunobiology in KD.

ASSESSING CLIMATE CHANGE IMPACTS ON THE STABILITY OF SMALL TIDAL INLETS: Part 2- DATA RICH ENVIRONMENTS.

Climate change (CC) is likely to affect the thousands of bar-built or barrier estuaries (here referred to as Small tidal inlets - STIs) around the world. Any such CC impacts on the stability of STIs, which governs the dynamics of STIs as well as that of the inlet-adjacent coastline, can result in significant socio-economic consequences due to the heavy human utilisation of these systems and their surrounds. This article demonstrates the application of a process based snap-shot modelling approach, using the coastal morphodynamic model Delft3D, to 3 case study sites representing the 3 main STI types; Permanently open, locationally stable inlets (Type 1), Permanently open, alongshore migrating inlets (Type 2) and Seasonally/Intermittently open, locationally stable inlets (Type 3). The 3 case study sites (Negombo lagoon - Type 1, Kalutara lagoon - Type 2, and Maha Oya river - Type 3) are all located along the southwest coast of Sri Lanka. After successful hydrodynamic and morphodynamic model validation at the 3 case study sites, CC impact assessment are undertaken for a high end greenhouse gas emission scenario. Future CC modified wave and riverflow conditions are derived from a regional scale application of spectral wave models (WaveWatch III and SWAN) and catchment scale applications of a hydrologic model (CLSM) respectively, both of which are forced with IPCC Global Climate Model output dynamically downscaled to ~ 50 km resolution over the study area with the stretched grid Conformal Cubic Atmospheric Model CCAM. Results show that while all 3 case study STIs will experience significant CC driven variations in their level of stability, none of them will change Type by the year 2100. Specifically, the level of stability of the Type 1 inlet will decrease from 'Good' to 'Fair to poor' by 2100, while the level of (locational) stability of the Type 2 inlet will also decrease with a doubling of the annual migration distance. Conversely, the stability of the Type 3 inlet will increase, with the time till inlet closure increasing by ~75%. The main contributor to the overall CC effect on the stability of all 3 STIs is CC driven variations in wave conditions and resulting changes in longshore sediment transport, not Sea level rise as commonly believed.

The immune-stimulation capacity of liposome-treated red blood cells.

Our in vivo studies on a rat model established safety of transfusing liposome-treated red blood cells (RBCs) but identified the potential for immune modulation as related to transfusion efficacy of liposome-treated RBCs. The aim of this study was at assessing the impact of liposome-induced membrane changes on the immune profile of liposome-treated RBCs by (a) evaluating their interaction with endothelial cells and monocytes; and (b) the resulting immune response derived from this interaction, in the form of cytokine release, adhesion molecules expression and phagocytosis. Unilamellar liposomes were synthesized to contain unsaturated phospholipids (1,2-dioleoyl-sn-glycero-3-phosphocholine [DOPC]:CHOL, 7:3 mol%). The human RBCs immune profile was assessed by incubating control and DOPC-treated RBCs with human umbilical vein endothelial cells (HUVECs) and monocytes. Cytokine release measured by Luminex technology, vascular cell adhesion molecule (VCAM)-1 and E-selectin on HUVECs measured by flow cytometry, and the erythrophagocytic activity of monocytes by monocyte monolayer assay (MMA) were determined. Fibroblast growth factor [FGF]-2 was the only cytokine released by HUVECs that remained increased after incubation with DOPC-treated RBCs compared to control throughout storage. The expression of both VCAM-1 (15.3 ± 5.6% versus 6.3 ± 0.9%, p = 0.008) and E-selectin (18.0 ± 6.3% versus 6.6 ± 0.7%, p = 0.004) by HUVECs were significantly increased after incubation with DOPC-treated RBCs at day 2 of storage. The MMA resulted in phagocytic indexes of zero for both control and DOPC-treated RBCs at day 2 and 42 of storage. The liposome treatment did not result in significant changes to the immune profile of stored DOPC-treated RBCs. These findings combined with previous in vivo results, make liposome treatment a potential candidate for application in RBC preservation and open the possibility for clinical use with other cell types.

Adaptive evolution of the lactose utilization network in experimentally evolved populations of Escherichia coli.

Adaptation to novel environments is often associated with changes in gene regulation. Nevertheless, few studies have been able both to identify the genetic basis of changes in regulation and to demonstrate why these changes are beneficial. To this end, we have focused on understanding both how and why the lactose utilization network has evolved in replicate populations of Escherichia coli. We found that lac operon regulation became strikingly variable, including changes in the mode of environmental response (bimodal, graded, and constitutive), sensitivity to inducer concentration, and maximum expression level. In addition, some classes of regulatory change were enriched in specific selective environments. Sequencing of evolved clones, combined with reconstruction of individual mutations in the ancestral background, identified mutations within the lac operon that recapitulate many of the evolved regulatory changes. These mutations conferred fitness benefits in environments containing lactose, indicating that the regulatory changes are adaptive. The same mutations conferred different fitness effects when present in an evolved clone, indicating that interactions between the lac operon and other evolved mutations also contribute to fitness. Similarly, changes in lac regulation not explained by lac operon mutations also point to important interactions with other evolved mutations. Together these results underline how dynamic regulatory interactions can be, in this case evolving through mutations both within and external to the canonical lactose utilization network.

Effects of Standardized Patient Simulation and Mobile Applications on Nursing Students' Clinical Competence, Self-Efficacy, and Cultural Competence: A Quasi-Experimental Study.

BACKGROUND: Simulation-based education has emerged as an effective approach in nursing education worldwide. We aimed to evaluate the effectiveness of a surgical nursing education program based on a simulation using standardized patients and mobile applications among nursing students. METHODS: A mixed-methods design with a quasi-experimental longitudinal approach and focus group interviews was employed. The data were collected from 130 third-year nursing students at three different time points who were equally divided into experimental and control groups. This study measured the level of clinical surgical nursing competence, self-efficacy in clinical performance, cultural competence, and satisfaction with simulation experience. Four focus group interviews were conducted using open-ended questions to explore the participants' perspectives on the course's efficacy and satisfaction. RESULTS: There were statistically significant differences in clinical surgical nursing competence (F = 8.68, p < 0.001), self-efficacy in clinical performance (F = 13.56, p < 0.001), and cultural competence (F = 10.35, p < 0.001) across time between the intervention and control groups. Student satisfaction with the simulation-based training was high, particularly regarding debriefing and reflection, with an overall mean satisfaction level of 4.25 (0.40). Students' perspectives regarding integrated hybrid training are categorized into three themes: educational achievement, dynamic learning experiences, and satisfaction and suggestion. CONCLUSION: Simulation-based learning provides a dynamic and immersive educational experience that enables undergraduate nursing students to develop and refine essential clinical skills while also fostering confidence and cultural competence.

Mercury increases IL-1ß and IL-18 secretion and intensifies coronary arteritis in an animal model of Kawasaki disease.

Kawasaki disease (KD) is a multisystem vasculitis that predominantly targets the coronary arteries in young children. Epidemiological data suggest both environmental and genetic factors contribute to the susceptibility and severity of the disease. Mercury (Hg) is a known environmental pollutant and a Ca2+ signaling modulator. Ca2+ signaling regulates the activation of NLRP3 inflammasome. Using the Lactobacillus casei cell wall extract (LCWE) induced coronary arteritis mouse model of KD; we studied the effect of mercury on inflammasome activation and its impact on the immunopathogenesis of KD. Mercury enhances the expression of inflammasome activation resulting in caspase-1 mediated secretion of IL-1ß and IL-18 cytokines. In vivo, the administration of mercury together with disease inducing LCWE exacerbates disease resulting in increased incidence and severity of coronary arteritis compared to LCWE alone. Mercury can act as a novel danger signal modulating Ca2+ signaling to increase IL-1ß and IL-18 secretion and intensifies coronary arteritis in an animal model of KD.

An assessment of whether long-term global changes in waves and storm surges have impacted global coastlines.

A common inference in research studies of observed and projected changes in global ocean wave height and storm surge, is that such changes are potentially important for long-term coastal management. Despite numerous studies of the impacts of anthropogenic climate change on trends in global wind and waves, a clear link to impacts on sandy coastlines, at global scale, is yet to be demonstrated. This study presents a first-pass assessment of the potential link between historical trends in global wave and storm surge values and recession/progradation rates of sandy coastlines since the 1980s. Global datasets of waves, surge and shoreline change rate are used for this purpose. Over the past 30 + years, we show that there have been clear changes in waves and storm surge at global scale. The data, however, does not show an unequivocal linkage between trends in wave and storm surge climate and sandy shoreline recession/progradation. We conclude that these long-term changes in oceanographic parameters may still be too small to have a measurable impact on shoreline recession/progradation and that primary drivers such as ambient imbalances in the coastal sediment budget may be masking any such linkages.

Assessing coastline recession for adaptation planning: sea level rise versus storm erosion.

The Sixth Assessment report (AR6) of the Intergovernmental Panel on Climate Change (IPCC) states with high confidence that most sandy coasts around the world will experience an increase in coastal erosion over the twenty-first century. An increase in long term coastal erosion (coastline recession) along sandy coasts can translate into massive socio-economic impacts, unless appropriate adaptation measures are implemented in the next few decades. To adequately inform adaptation measures, it is necessary to have a good understanding of the relative importance of the physical processes driving coastline recession, as well as of linkages between consideration (or not) of certain processes and the level of risk tolerance; understandings that are hitherto lacking. Here, we apply the multi-scale Probabilistic Coastline Recession (PCR) model to two end-member sandy coastal types (swell dominated and storm dominated), to investigate where and when coastline recession projections are dominated by the differential contributions from Sea Level Rise (SLR) and storm erosion. Results show that SLR substantially increases the projected end-century recession at both types of coasts and that projected changes in the wave climate have only a marginal impact. An analysis of the Process Dominance Ratio (PDR), introduced here, shows that the dominance of storm erosion over SLR (and vice versa) on total recession by 2100 depends on both the type of the beach and the risk tolerance levels. For moderately risk-averse decisions (i.e. decisions accounting only for high exceedance probability recessions and hence do not account for very high amounts of potential recession-for example, the placement of temporary summer beach cabins), additional erosion due to SLR can be considered as the dominant driver of end-century recession at both types of beaches. However, for more risk-averse decisions that would typically account for higher potential recession (i.e. lower exceedance probability recessions), such as the placement of coastal infrastructure, multi-storey apartment buildings etc., storm erosion becomes the dominant process. The results of this study provide new insights on which physical processes need to be considered when and where in terms of numerical modelling efforts needed for supporting different management decisions, potentially enabling more streamlined and comprehensive assessments of the efficacy of coastal adaptation measures.

The fibrillogenic L178H variant of apolipoprotein A-I forms helical fibrils.

A number of amyloidogenic variants of apoA-I have been discovered but most have not been analyzed. Previously, we showed that the G26R mutation of apoA-I leads to increased ß-strand structure, increased N-terminal protease susceptibility, and increased fibril formation after several days of incubation. In vivo, this and other variants mutated in the N-terminal domain (residues 26 to ∼90) lead to renal and hepatic accumulation. In contrast, several mutations identified within residues 170 to 178 lead to cardiac, laryngeal, and cutaneous protein deposition. Here, we describe the structural changes in the fibrillogenic variant L178H. Like G26R, the initial structure of the protein exhibits altered tertiary conformation relative to wild-type protein along with decreased stability and an altered lipid binding profile. However, in contrast to G26R, L178H undergoes an increase in helical structure upon incubation at 37°C with a half time (t(1/2)) of about 12 days. Upon prolonged incubation, the L178H mutant forms fibrils of a diameter of 10 nm that ranges in length from 30 to 120 nm. These results show that apoA-I, known for its dynamic properties, has the ability to form multiple fibrillar conformations, which may play a role in the tissue-specific deposition of the individual variants.

Inhibition of transforming growth factor ß worsens elastin degradation in a murine model of Kawasaki disease.

Kawasaki disease (KD) is an acute inflammatory illness marked by coronary arteritis. However, the factors increasing susceptibility to coronary artery lesions are unknown. Because transforming growth factor (TGF) ß increases elastin synthesis and suppresses proteolysis, we hypothesized that, in contrast to the benefit observed in aneurysms forming in those with Marfan syndrome, inhibition of TGF-ß would worsen inflammatory-induced coronary artery lesions. By using a murine model of KD in which injection of Lactobacillus casei wall extract (LCWE) induces coronary arteritis, we show that LCWE increased TGF-ß signaling in the coronary smooth muscle cells beginning at 2 days and continuing through 14 days, the point of peak coronary inflammation. By 42 days, LCWE caused fragmentation of the internal and external elastic lamina. Blocking TGF-ß by administration of a neutralizing antibody accentuated the LCWE-mediated fragmentation of elastin and induced an overall loss of medial elastin without increasing the inflammatory response. We attributed these increased pathological characteristics to a reduction in the proteolytic inhibitor, plasminogen activator inhibitor-1, and an associated threefold increase in matrix metalloproteinase 9 activity compared with LCWE alone. Therefore, our data demonstrate that in the coronary arteritis associated with KD, TGF-ß suppresses elastin degradation by inhibiting plasmin-mediated matrix metalloproteinase 9 activation. Thus, strategies to block TGF-ß, used in those with Marfan syndrome, are unlikely to be beneficial and could be detrimental.

2,3,7,8-Tetrachlorodibenzo-p-dioxin-induced MUC5AC expression: aryl hydrocarbon receptor-independent/EGFR/ERK/p38-dependent SP1-based transcription.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent environmental toxicant. Epidemiological studies have associated TCDD exposure with the development of chronic obstructive pulmonary disease, which is manifested by mucous/goblet cell hyperplasia. The purpose of this research was to elucidate the pathway/mechanisms that lead to TCDD-induced gene expression in both primary normal human bronchial epithelial cells and an immortalized cell line, HBE1, under air-liquid interface conditions. TCDD exposure induced a time-dependent elevation of MUC5AC mRNA and protein synthesis, and cytochrome p450 1A1 (CYP1A1) expression in these cells. Treatment with an aryl hydrocarbon receptor antagonist had no effect on TCDD-induced MUC5AC expression, but significantly suppressed CYP1A1 induction. However, treatments with inhibitors of signaling pathways and the expression of dominant negative mutants of epidermal growth factor receptor (EGFR), extracellular signal-regulated kinase (ERK) and p38, but not the inhibition of c-Jun N-terminal kinase pathway, abrogated MUC5AC induction, but not that of CYP1A1. These effects also occurred at the MUC5AC promoter-reporter level using the chimeric construct for a transient transfection study. Western blot analysis confirmed the phosphorylation of activated EGFR, ERK, and p38 signaling molecules, but not the c-Jun N-terminal kinase, in cells after TCDD exposure. Specificity protein 1 (Sp1) phosphorylation also occurred in cells after TCDD exposure. Both MUC5AC expression and the promoter activity were inhibited by mithramycin A, an inhibitor specific to Sp1-based transcription. These results lead to the conclusion that TCDD induced MUC5AC expression through a noncanonical aryl hydrocarbon receptor-independent, EGFR/ERK/p38-mediated signaling pathway-mediated/Sp1-based transcriptional mechanism.

Determining contamination level of heavy metals in road dust from busy traffic areas with different characteristics.

This study identified the levels and sources of heavy metal contamination in road dust from busy traffic areas in a typical industrial city in Korea. This study compared the total concentrations, as determined by aqua regia digestions and atomic absorption spectroscopy, of cadmium (Cd), copper (Cu), lead (Pb), zinc (Zn) and nickel (Ni) in the road dust from areas with different characteristics such as traffic rotaries, downtown areas, circulation roads, and asphalt and concrete highways. The contamination levels of the heavy metals in the road dust were evaluated using the contamination factor and the degree of contamination. The contamination levels of the heavy metals in the road dust were highly dependent on traffic volume and atmospheric dispersion from traffic rotaries. Industrial emissions and the frequency of brake use and vehicles coming to a complete stop were additional factors that affected the contamination levels in downtown areas. The concrete highway had higher contamination levels of the heavy metals than the asphalt highway. Vehicle speed was also a strong contributing factor to the degree of contamination of heavy metals in the road dust from the circulation roads and highways.

Probabilistic projections of the stability of small tidal inlets at century time scale using a reduced complexity approach.

Climate change is widely expected to affect the thousands of small tidal inlets (STIs) dotting the global coastline. To properly inform effective adaptation strategies for the coastal areas in the vicinity of these inlets, it is necessary to know the temporal evolution of inlet stability over climate change time scales (50-100 years). As available numerical models are unable to perform continuous morphodynamic simulations at such time scales, here we develop and pilot a fast, probabilistic, reduced complexity model (RAPSTA - RAPid assessment tool of inlet STAbility) that can also quantify forcing uncertainties. RAPSTA accounts for the key physical processes governing STI stability and for climate change driven variations in system forcing. The model is very fast, providing a 100 year projection in less than 3 seconds. RAPSTA is demonstrated here at 3 STIs, representing the 3 main Types of STIs; Permanently open, locationally stable inlet (Type 1); Permanently open, alongshore migrating inlet (Type 2); Seasonally/Intermittently open, locationally stable inlet (Type 3). Model applications under a high greenhouse gas emissions scenario (RCP 8.5), accounting for forcing uncertainties, show that while the Type 1 STI will not change type over the twenty-first century, the Type 2 inlet may change into a more unstable Type 3 system around mid-century, and the Type 3 STI may change into a less unstable Type 2 system in about 20 years from now, further changing into a stable Type 1 STI around mid-century. These projections underscore the need for future adaptation strategies to remain flexible.

Twenty-first-century projections of shoreline change along inlet-interrupted coastlines.

Sandy coastlines adjacent to tidal inlets are highly dynamic and widespread landforms, where large changes are expected due to climatic and anthropogenic influences. To adequately assess these important changes, both oceanic (e.g., sea-level rise) and terrestrial (e.g., fluvial sediment supply) processes that govern the local sediment budget must be considered. Here, we present novel projections of shoreline change adjacent to 41 tidal inlets around the world, using a probabilistic, reduced complexity, system-based model that considers catchment-estuary-coastal systems in a holistic way. Under the RCP 8.5 scenario, retreat dominates (90% of cases) over the twenty-first century, with projections exceeding 100 m of retreat in two-thirds of cases. However, the remaining systems are projected to accrete under the same scenario, reflecting fluvial influence. This diverse range of response compared to earlier methods implies that erosion hazards at inlet-interrupted coasts have been inadequately characterised to date. The methods used here need to be applied widely to support evidence-based coastal adaptation.

Single and Combinative Impacts of Healthy Eating Behavior and Physical Activity on COVID-19-like Symptoms among Outpatients: A Multi-Hospital and Health Center Survey.

BACKGROUND: Healthy eating and physical activity are effective non-pharmacological approaches to boost immune function and contain the pandemic. We aimed to explore the associations and interactions between physical activity and healthy eating behavior with COVID-19-like symptoms (Slike-CV19S). METHODS: A cross-sectional study was conducted on 3947 outpatients, from 14 February to 2 March 2020, at nine health facilities in Vietnam. Data collection included sociodemographic characteristics, healthy eating behavior (using the healthy eating score (HES) questionnaire), physical activity (using the short form international physical activity questionnaire), and Slike-CV19S. The associations and interactions were tested using logistic regression models. RESULTS: Frequent intake of fruits (OR = 0.84; p = 0.016), vegetables (OR = 0.72; p = 0.036), and fish (OR = 0.43; p < 0.001) were associated with a lower Slike-CV19S likelihood, as compared with infrequent intake. Patients with higher HES levels (OR = 0.84; p = 0.033 for medium HES; OR = 0.77; p = 0.006 for high HES) or being physically active (OR = 0.69; p < 0.001) had a lower Slike-CV19S likelihood, as compared to those with low HES or physical inactivity, respectively. Patients with medium HES who were physically active (OR = 0.69; p = 0.005), or with high HES and physically active (OR = 0.58; p < 0.001), had a lower Slike-CV19S likelihood, as compared to those with low HES and physical inactivity. CONCLUSIONS: Healthy eating behavior and physical activity showed single and combinative impacts on protecting people from Slike-CV19S. Strategic approaches are encouraged to improve healthy behaviors, which may further contribute to containing the pandemic.