Segmentation of hyphae and yeast in fungi-infected tissue slice images and its application in analyzing antifungal blue light therapy.

Candida albicans is a pathogenic fungus that undergoes morphological transitions between hyphal and yeast forms, adapting to diverse environmental stimuli and exhibiting distinct virulence. Existing research works on antifungal blue light (ABL) therapy have either focused solely on hyphae or neglected to differentiate between morphologies, obscuring potential differential effects. To address this gap, we established a novel dataset of 150 C. albicans-infected mouse skin tissue slice images with meticulously annotated hyphae and yeast. Eleven representative convolutional neural networks were trained and evaluated on this dataset using seven metrics to identify the optimal model for segmenting hyphae and yeast in original high pixel size images. Leveraging the segmentation results, we analyzed the differential impact of blue light on the invasion depth and density of both morphologies within the skin tissue. U-Net-BN outperformed other models in segmentation accuracy, achieving the best overall performance. While both hyphae and yeast exhibited significant reductions in invasion depth and density at the highest ABL dose (180 J/cm2), only yeast was significantly inhibited at the lower dose (135 J/cm2). This novel finding emphasizes the importance of developing more effective treatment strategies for both morphologies.

We studied the effects of blue light therapy on hyphal and yeast forms of Candida albicans. Through image segmentation techniques, we discovered that the changes in invasion depth and density differed between these two forms after exposure to blue light.

LncRNA HOTAIR regulates anoikis-resistance capacity and spheroid formation of ovarian cancer cells by recruiting EZH2 and influencing H3K27 methylation.

This study aims to investigate the role of the long non-coding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) in the regulation of anoikis resistance of ovarian cancer cells, a prerequisite for metastasis and chemoresistance in ovarian cancer cells. Ovarian cancer SKOV3 cells were cultured in an ultra-low attachment system to establish an anoikis model. The relationship between cellular anoikis capability and HOTAIR expression level was studied by flow cytometry and RT-PCR. The ability of spheroid formation, migration, and invasion of the suspended cells was assessed following the knockdown of HOTAIR expression. The expression of EZH2, H3K27me3, representative targets of EZH2, and anoikis-related biomarkers was also detected. An increase in the duration of suspension culture time rendered the SKOV3 cells anoikis-resistant with a significantly lower apoptotic rate compared to the adherent cells. HOTAIR expression in the suspension cells increased significantly, while that in the adherent cells did not. Following small interfering RNA (siRNA)-mediated knockdown of HOTAIR expression, the abilities of anoikis resistance, migration, and invasion decreased in the suspension cells. Knockdown of HOTAIR levels also reduced the spheroid forming ability of the tumor cells in continuous suspension cultures. Moreover, EZH2 expression correlated with HOTAIR expression, thus regulating the expression of miR-193a and DOK2 via introducing H3K27me3. Western blot analysis of anoikis-related markers showed that N-cadherin, ZEB1, and TWIST1 were downregulated following inhibition of HOTAIR, while E-cadherin and ErbB3 were upregulated. In conclusion, HOTAIR enhances the anoikis resistance and spheroid forming ability of ovarian cancer cells by recruiting EZH2 and influencing H3K27 methylation that may contribute to migration, invasion, and chemoresistance of ovarian cancer cells.

Outdoor thermal comfort and adaptive behaviors in the residential public open spaces of winter cities during the marginal season.

In winter cities, outdoor seasons are highly valued due to the long cold winter. By improving the outdoor thermal environment during marginal seasons, outdoor seasons may be extended. Therefore, outdoor thermal comfort and adaptive behaviors during marginal seasons should be considered. Three representative residential public open spaces in Harbin, a typical winter city, were selected to conduct an empirical study. Meteorological measurements and rudimentary questionnaires were administered and observations were conducted to explore outdoor thermal comfort and adaptive behaviors. Three important conclusions were obtained from the survey. The result from the questionnaire surveys showed that users of public spaces generally believed that "warm" was comfortable during the spring marginal season of the winter cities. The 90% thermal acceptable physiologically equivalent temperature (PET) range, which was calculated using meteorological measurements and questionnaire results, was more than 10.2 °C for this time period in the winter cities. This threshold value was much lower than that of temperate and subtropical zones, indicating that the outdoor thermal comfort of users in the winter cities had regional characteristics. Moreover, users engaged in static vs. dynamic activities showed different sensitivities to thermal environments. The users' location selection showed a strong dependence on microclimate rather than on the activity-supported facilities; when microclimate conditions changed, users made accommodations by moving to sunny areas or performing other adaptive behaviors, and thus, space utilization changed. These findings can inform thermal comfort-oriented planning and design from the perspectives of microclimate regulations, site planning, and activities in the residential public open spaces of winter cities.

Construction of the "Full Path" of restorative effects on older adults' mental health in parks under seasonal differences: taking Changchun as an example.

With the aging and older adults' mental health problems in China, more attention has been paid to the restorative environment. As an important restorative environment in the city, the mental health restorative effect of park environment has been confirmed. However, further exploration is needed to determine whether winter parks have positive effects, their differences from non-winter parks, and the specific pathways of these effects. Therefore, this study constructed a "full path" for the restorative effects of older adults' mental health in parks under seasonal differences, including four components: perceived environment, affective feedback, behavioral feedback, and restorative effect, forming four pathways. Based on this, this study obtained 211 and 240 sample data in winter and non-winter parks, and verified the validity of various hypotheses and mediation paths using structural equation models. It found that: (1) overall restorative effects existed in different seasons; (2) in winter, perceived environmental assessment was not a direct antecedent of restorative effects, and affective feedback and Moderate and Vigorous Physical Activity (MVPA) feedback were important mediating factors, and the chain mediated pathway existed; (3) in non-winter, both direct, indirect and chain mediated effects existed, and affective feedback and Low Physical Activity (LPA) feedback were important mediating factors. Based on this, this study divided parks into "affective inducing" and "behavioral promoting" types, and proposed corresponding planning priorities to positively intervene in planning and design practices.

Impact of urban form on carbon emissions of residents in counties: evidence from Yangtze River Delta, China.

Urban form is a key factor affecting carbon emissions. Accurately estimating the impact of urban form on the carbon emissions of residents (CER) is an important prerequisite for China to adopt effective low-carbon spatial planning strategies and respond to climate change. However, counties mainly account for China's energy consumption, and the relationship between their urban form and the CER remains unclear, limiting their low-carbon development. Therefore, in this study, the PLS-SEM model and data from 90 counties in the Yangtze River Delta are used to determine the extent and ways that urban form affects the CER. The model considers the impact of both geometric-aspect urban form factors (urban scale, compactness, spatial structure, and urban shape) and built environment-aspect urban form factors (public service facilities, urban greening, road traffic, public transportation, and urban energy infrastructure) on the CER. The results indicate that urban form factors related to the built environment (public service facilities, urban greening, road systems, and municipal infrastructure) have a direct impact on the CER. Geometric-aspect urban form factors (size, compactness, spatial structure, and shape) not only directly affect the CER but also indirectly affect the CER by altering built environment-aspect urban form factors. This study identifies the complex relationship between urban form and the CER, facilitating the coordinated integration of multiple elements and providing a basis for the formulation of low-carbon spatial planning strategies for counties.

Correlation between dysbiosis of vaginal microecology and endometriosis: A systematic review and meta-analysis.

BACKGROUND: Endometriosis, a complex gynecological condition, involves inflammation and immune dysregulation. The vaginal microbiota, characterized by its diversity, is an integral part of the vaginal microecology-interacting with vaginal anatomy, the endocrine system, and local mucosal immunity. Imbalances in this microecology are known to precipitate various inflammatory diseases. Despite extensive research, the connection between vaginal microbiota dysbiosis and endometriosis remains a subject of debate. Our study assesses the association between vaginal microecology dysbiosis and endometriosis. METHODS: We systematically searched major electronic databases in English, including Embase, PubMed, The Cochrane Library, MEDLINE (Ovid), BIOSIS (Ovid), China National Knowledge Infrastructure (CNKI), and Wanfang, up to August 15, 2023. Selected articles underwent screening based on predefined inclusion and exclusion criteria. Normal vaginal microecology was defined as a negative Amsel/Spiegel test or Nugent score of 0-3, or Lactobacillus predominance determined by 16S rRNA gene amplification sequencing. Deviations from this norm were classified as dysbiosis, further categorized into bacterial vaginosis (BV) and intermediate BV. Data analysis utilized Revman 5.4, with effect sizes presented as Odds Ratios (OR) and 95% Confidence Intervals (CI). RESULTS: Out of 1081 articles, eight met the inclusion criteria. Utilizing fixed-effect models due to low heterogeneity, the analysis revealed a positive association between dysbiosis and endometriosis (OR = 1.17, 95% CI 0.81-1.70; I2 = 0%), but showed a slight negative association between normal vaginal microecology with endometriosis (OR = 0.90, 95% CI 0.55-1.46; I2 = 29%). However, the association was not significant. Subgroup and sensitivity analyses corroborated the stability of these associations. CONCLUSION: A positive correlation exists between vaginal microecology dysbiosis and endometriosis, notably with intermediate BV. However, the mechanisms underpinning this relationship remain elusive, highlighting the need for further research to overcome limitations. TRIAL REGISTRATION: Registration number: CRD42023445163.

[Determination of chlorogenic acid, rutin, scopoletin and total polyphenol in tobacco by Fourier transform near infrared spectroscopy].

The objective of the present study was to investigate the feasibility of predicting chlorogenic acid, rutin, scopoletin and total polyphenol in tobacco by Fourier transform near-infrared (FT-NIR) spectroscopy. The partial least squares(PLS) regression method, second derivative and Norris derivative filter were applied in the NIR spectroscopy prediction of chlorogenic acid, rutin, scopoletin and total polyphenol in the range of 7 500 to 4 000 cm(-1). For chlorogenic acid, rutin, scopoletin and total polyphenol, the determination coefficients were 0.976 6, 0.941 9, 0.957 1 and 0.966 6, respectively. The SEP/SEC values for them were < 1.2, and the SD/SEP values for them were > 2. The root mean square error of cross validation (RMSECV) of the four calibration models were 1.938 9, 1.046 2, 0.047 9 and 2.745 2, respectively. NIR spectroscopy was compared with the conventional methods. The results show that the two methods showed no significant difference at the significant level of 0.05. NIR spectroscopy technology can accurately analyze chlorogenic acid, rutin, scopoletin and total polyphenol in tobacco.

The Effects of Winter Parks in Cold Regions on Cognition Recovery and Emotion Improvement of Older Adults: An Empirical Study of Changchun Parks.

Urban parks are one of the primary settings for older adults to exercise, and their health benefits have been confirmed by a large number of studies. However, with the increased social attention to mental health, there is not enough research on the short-term mental health recovery of older adults in parks. Meanwhile, the health recovery effects of winter parks in special climate areas have not been well explored. This study aimed to explore the effects of winter parks in cold regions on the short-term mental health recovery of older adults and the potential predictors of these effects, including individual status, park characteristics, and behavioral characteristics. This study divided short-term mental health recovery into cognitive recovery and emotional improvement, and selected the digit span test and 10 kinds of emotional expression as the experimental methods, recruited 92 older adults from 6 parks in Changchun, and compared the pre-test and post-test results for evaluation. The results showed that winter parks in cold cities still had short-term cognitive recovery and emotional improvement effects on older adults. The main park characteristic factors affecting the overall cognitive recovery were the evergreen vegetation area and the existence of structures, and that which affected the overall emotional improvement was the main pathway length. Furthermore, individual conditions, including gender, age, physical health, living and customary conditions, and park characteristics, including park type, park area, main pathway length, square area, equipment area, evergreen vegetation area, the presence of water, and structures, all related to short-term mental health recovery effects. Among behavioral characteristics, stay time in parks and MVPA (Moderate and Vigorous Physical Activity) times were also related to certain effects, but behavior type was not.

The effect of desloratadine on patch test reactions in Chinese patients.

BACKGROUND: Few data on the effect of antihistamines on patch test results in Chinese patients are currently available. OBJECTIVES: To evaluate the effect of desloratadine on patch test reactions. METHODS: Patients known to have at least one strongly positive (+ +) test with an allergen were re-patch tested after 14 to 70 days (average time interval 26.3 days) of administering oral desloratadine 5 mg twice a day for 5 days before and during the test. Patch testing was performed with the previously recognized allergen according to the guidelines of the ICDRG. The -to + + + system was converted into numeric values (0, 1, 2, 3, 4) for statistic evaluation. RESULTS: Of the 58 chambers (47 patients), which were all strongly positive (+ +) during the 1st patch test, the situation was unchanged in 51 chambers; 4 + reactions and 2 + + + reactions were observed; and 1 chamber was negative. There was no statistically significant difference when comparing the scores of the 1st assessment with those of the 2nd (p = 0.206). If the patch test reaction of the patient who dropped out of the trial had changed from strongly positive (+ +) to negative, there would still have been no statistically significant difference between the score of the 1st assessment with those of the 2nd ( p = 0.107). CONCLUSIONS: The reaction of a patch test is not hampered by doubling dose of desloratadine. The anti-inflammatory effects of desloratadine on patch test reaction may be limited.

Correction: Polysaccharides from Ulva prolifera O.F. Müller inhibit cell proliferation via activating MAPK signaling in A549 and H1650 cells.

Correction for 'Polysaccharides from Ulva prolifera O.F. Müller inhibit cell proliferation via activating MAPK signaling in A549 and H1650 cells' by Juan Juan Yang et al., Food Funct., 2021, 12, 6915-6924, https://doi.org/10.1039/D1FO00294E.

Overexpression of Twist1 in vascular endothelial cells promotes pathological retinal angiogenesis in mice.

Retinal angiogenesis is a critical process for normal retinal function. However, uncontrolled angiogenesis can lead to pathological neovascularization (NV), which is closely related to most irreversible blindness-causing retinal diseases. Understanding the molecular basis behind pathological NV is important for the treatment of related diseases. Twist-related protein 1 (TWIST1) is a well-known transcription factor and principal inducer of epithelial-mesenchymal transition (EMT) in many human cancers. Our previous study showed that Twist1 expression is elevated in pathological retinal NV. To date, however, the role of TWIST1 in retinal pathological angiogenesis remains to be elucidated. To study the role of TWIST1 in pathological retinal NV and identify specific molecular targets for antagonizing pathological NV, we generated an inducible vascular endothelial cell (EC)-specific Twist1 transgenic mouse model ( Tg-Twist1 iEC+ ). Whole-mount retinas from Tg-Twist1 iEC+ mice showed retarded vascular progression and increased vascular density in the front end of the growing retinal vasculature, as well as aneurysm-like pathological retinal NV. Furthermore, overexpression of Twist1 in the ECs promoted cell proliferation but disturbed cell polarity, thus leading to uncontrolled retinal angiogenesis. TWIST1 promoted pathological NV by activating the Wnt/ß-catenin signaling pathway and inducing the expression of NV formation-related genes, thereby acting as a 'valve' in the regulation of pathological angiogenesis. This study identified the critical role of TWIST1 in retinal pathological NV, thus providing a potential therapeutic target for pathological NV.

Pharmacokinetics and pharmacodynamics of TBR-652, a novel CCR5 antagonist, in HIV-1-infected, antiretroviral treatment-experienced, CCR5 antagonist-naïve patients.

TBR-652 is a novel CCR5 antagonist with potent in vitro anti-HIV activity. The objective of this study was to determine the pharmacokinetics (PK) and pharmacodynamics (PD) of TBR-652 in HIV-1-infected, antiretroviral treatment-experienced, CCR5 antagonist-naïve patients. A double-blind, placebo-controlled, randomized, dose-escalating study of TBR-652 monotherapy given once daily orally for 10 days was performed, followed by a 40-day follow-up period. Approximately 10 patients/dose level received 25, 50, 75, 100, and 150 mg TBR-652 or placebo (4:1). Blood was collected at different intervals for PK and HIV-1 RNA assessments. PK analysis of TBR-652 was performed using noncompartmental methods. PK/PD was modeled using a maximum inhibitory effect model (E(max)) and 50% inhibitory concentrations (IC50). TBR-652 was well absorbed in the systemic circulation. TBR-652 concentration levels declined slowly, with mean elimination half-lives ranging from 22.5 to 47.62 h across dose levels. TBR-652 treatment resulted in potent, dose-dependent decreases in viral load, with statistically significant decreases in nadir HIV-1 RNA compared to baseline for all dose levels. Suppression of HIV-1 RNA persisted over the 40-day follow-up period. A steep exposure-effect relationship was observed, with an E(max) of -1.43 log10 copies/ml and IC50 of 13.1 ng/ml. TBR-652 was generally safe and well tolerated at all dose levels studied. Short-term monotherapy treatments of TBR-652 in HIV-1-infected patients resulted in promising PK and PD results, with a clear exposure-response relationship at the current dose levels studied. Data from this study support further development of TBR-652 in HIV-infected patients.

Impact of the COVID-19 pandemic: Insights from vacation rentals in twelve mega cities.

Coronavirus disease 2019 (COVID-19) is a challenging global problem. COVID-19 has caused shocks to various urban systems, and the tourism industry is no exception. We analyzed the impact on vacation rentals by conducting diachronic data mining on nearly 10 GB of rental data (calendar, listings, and reviews) in twelve highly internationalized megacities distributed across Asia, Europe, America, and Oceania based on the data set from the Inside Airbnb website. All twelve cities were adversely affected. The specific time of the impact is related to the pandemic's outbreak and enforced lockdowns policies. Affected by the epidemic, reservation rates decreased, tourists preferred renting in suburbs instead of city centers, the proportion of foreign tourists in all destinations dropped sharply, tourist sentiment scores fluctuated dramatically especially among foreigners, and people focused less on tourism related activities. This study reveals the changing illustrations of vacation rentals in highly internationalized megacities under the pandemic's influence. It offers a methodological assessment framework to monitor the hospitality sector over time and aims to serve as a reference for preparedness in similar cities worldwide.

Sortilin regulates keratinocyte proliferation and apoptosis through the PI3K-AKT signaling pathway.

Sortilin is found to regulate proliferation and death of different cells, while its role in regulating keratinocyte proliferation and apoptosis is still unknown. In this study, we found that sortilin levels significantly increased in psoriasis patients, and sortilin suppression eliminated the proliferation of HaCaT cells induced by M5 cocktail solution and enhanced the levels of cleaved caspase 3 protein and the Bax/Bcl-2 ratio; however, levels of p-PI3K and p-AKT were decreased. In addition, sortilin silencing remitted the characteristic changes associated with psoriasis-like skin lesions. In summary, suppressed sortilin expression helped inhibit keratinocyte proliferation in HaCaT cells by inactivating PI3K/AKT signaling, which provides a new target for the therapy of psoriasis.

Polysaccharides from Ulva prolifera O.F. Müller inhibit cell proliferation via activating MAPK signaling in A549 and H1650 cells.

Reactive oxygen species (ROS), especially hydrogen peroxide (H2O2), have recently been reported to cause a significant increase in the production and expression of matrix metalloproteinases (MMPs), which are closely correlated with lung cancer metastasis. The aim of the present study is to determine the inhibitory effects of a polysaccharide isolated from Ulva prolifera O.F. Müller (U. prolifera) on the invasive potential of non-small cell lung cancer (NSCLC) cells, and further to explore the underlying mechanisms connected to that potential. The data showed that increased MMP-9 resulting from H2O2 exposure was mediated by activating mitogen-activated protein kinases (MAPKs). Pre-treatment with polysaccharides suppressed the activation of H2O2-mediated MAPK pathways and cell invasion. Hence, MMP-9 production triggered by H2O2 was demonstrated by activating MAPK signaling in a Myc-dependent manner. Taken together, these results suggested that polysaccharides suppress H2O2-induced cell invasion by inhibiting Myc-mediated MMP-9 gene transcription through the MAPK signaling pathway in A549 and NCI-H1650 cells. Our data also suggested that polysaccharides may be useful in minimizing the development of lung cancer metastasis. In the future, pretreatment with polysaccharides because of their antioxidant properties might be beneficial to enhance surgical outcomes.

Exploring the Relationship between Green Space in a Neighbourhood and Cardiovascular Health in the Winter City of China: A Study Using a Health Survey for Harbin.

A severely cold climate has a significant impact on cardiovascular health, involving temperature, air environment, exercise and diet. Existing studies have revealed that green space, as an important health resource, may play a positive role in promoting cardiovascular health through the air environment and exercise. Studies focusing on the correlation between green space and cardiovascular health are rarely carried out in winter cities. The purpose of this paper is to take a winter city in China as an empirical case to explore the correlation between green space in a neighbourhood and cardiovascular health in a representative sample at the neighbourhood level, combining the results with Urban Residential Area Planning and Design Standards (GB50180-2018) in China and the existing research. The results showed that green space characteristics of a neighbourhood were related to cardiovascular disease and some of its risk factors. In neighbourhoods with a Green Space Ratio lower than 28%, residents had a higher risk of physical inactivity, overweight or obesity, hypertension and stroke. In neighbourhoods with a Green View Index lower than 15%, residents had a higher risk of physical inactivity, overweight/obesity, hypertension, dyslipidemia and stroke. A correlation was found between evergreen tree configuration type and the prevalence of overweight/obesity and hypertension. No correlation was found between the type of sports field and cardiovascular disease and its risk factors, except for hypertension. Residents' cardiovascular health scores also showed significant differences among neighbourhoods with different green space characteristics. Intervention efforts may benefit from emphasising the importance of improving the Green Space Ratio and Green View Index effectively in a neighbourhood to reduce the risk of cardiovascular disease.

Impact of Urban Morphology and Climate on Heating Energy Consumption of Buildings in Severe Cold Regions.

This study aims to acquire a better understanding of the quantitative relationship between environmental impact factors and heating energy consumption of buildings in severe cold regions. We analyze the effects of five urban morphological parameters (building density, aspect ratio, building height, floor area ratio, and shape factor) and three climatic parameters (temperature, wind speed, and relative humidity) on the heating energy use intensity (EUI) of commercial and residential buildings in a severe cold region. We develop regression models using empirical data to quantitatively evaluate the impact of each parameter. A stepwise approach is used to ensure that all the independent variables are significant and to eliminate the effects of multicollinearity. Finally, a spatial cluster analysis is performed to identify the distribution characteristics of heating EUI. The results indicate that the building height, shape factor, temperature, and wind speed have a significant impact on heating EUI, and their effects vary with the type of building. The cluster analysis indicated that the areas in the north, east, and along the river exhibited high heating EUI. The findings obtained herein can be used to evaluate building energy efficiency for urban planners and heating companies and departments based on the surrounding environmental conditions.

Planning for Supportive Green Spaces in the Winter City of China: Linking Exercise of Elderly Residents and Exercise Prescription for Cardiovascular Health.

The elderly population have a high incidence of cardiovascular disease and are the main users of green spaces, such as city parks. Creating supportive green spaces for exercise for the elderly is of great significance to promote their cardiovascular health. The winter cities have a severely cold climate and high incidence of cardiovascular disease, while the elderly, especially those with cardiovascular disease, face more challenges when participating in exercise in the green spaces. In the context of the winter cities, the kinds of exercise the elderly participate in are more conducive to their cardiovascular health, and determining the factors of the green spaces that are supportive for exercise for cardiovascular health in the winter are of particular interest. Taking Harbin, a typical winter city in China, as an example, this study aims to identify the exercise characteristics of elderly residents in the green spaces in winter, to link them with the principles and contents of exercise prescription for cardiovascular health, to identify the deficient factors of the green spaces in supporting exercise for cardiovascular health, and to put forward optimization design implications. Mixed qualitative methods including interviews, a questionnaire, and field observation were used to identify special behavioral characteristics and spatial factors involving winter exercise in the green spaces among the elderly. The results showed that: (1) about 42.4% of the participants had a gap with the principles of exercise prescription for cardiovascular health. Their exercise items were generally consistent with the principle of low-intensity exercise, but some of them had the problems regarding early exercise time and insufficient exercise duration and frequency. (2) Insufficient supportive factors of the green spaces mainly included facilities allocation, comfort, safety, accessibility, and air quality. Facilities allocation involved walking paths, rehabilitation facilities, auxiliary facilities, and guidance facilities; comfort involved sunlight conditions of the exercise areas; safety involved slippery roads and sites with ice and snow and medical accidents; accessibility involved the proximity, the safety of connecting roads, and the movement of the elderly; air quality involved the planting of evergreen trees. Accordingly, the design implications were given in order to bridge the supportive gap of the green spaces for exercise for cardiovascular health in the elderly population.

Randomized Population Pharmacokinetic Analysis and Safety of Intravenous Acetaminophen for Acute Postoperative Pain in Neonates and Infants.

Intravenous administration of acetaminophen is an alternative to the oral and rectal routes, which may be contraindicated in particular clinical settings. This randomized, placebo-controlled study of intravenous acetaminophen (Ofirmev, Mallinckrodt Pharmaceuticals, Bedminster, New Jersey) in neonate and infant patients with acute postoperative pain assessed pharmacokinetics (PK) and safety, in addition to efficacy and pharmacodynamics of repeated doses administered over 24 hours. Neonate and infant patients (<2 years of age) who were undergoing surgery or had experienced a traumatic injury and were expected to need pain management for at least 24 hours were enrolled. Subjects were randomly assigned to receive intravenous acetaminophen low dose, intravenous acetaminophen high dose, or placebo. A population PK model of intravenous acetaminophen was updated by combining 581 samples from the current study of 158 neonate and infant subjects with results from a previously developed model. The individual predicted-versus-observed concentrations plots showed that the structural PK model fit the blood and plasma acetaminophen concentration-versus-time profiles in the active and placebo groups. Terminal elimination half-life was prolonged in neonates and younger infants and in intermediate and older infants similar to values in adults. When compared with placebo, total rescue opioid consumption was similar and significantly fewer intravenous acetaminophen patients prematurely discontinued because of treatment-emergent adverse events (P < .01). For intravenous acetaminophen, neonates receiving 12.5 mg/kg every 6 hours had PK profiles similar to younger, intermediate, and older infants, adolescents, and adults weighing <50 kg receiving 15 mg/kg every 6 hours and adults ≥ 50 kg receiving 1000 mg every 6 hours.

Reversal of ultraviolet B-induced immunosuppression by inhibition of the extracellular signal-regulated mitogen-activated protein kinase.

OBJECTIVE: Topical treatment of the specific inhibitor PD98059 (PD) for extracellular signal-regulated kinase (ERK)1/2 combined with ultraviolet B (UVB) exposure in an in vivo study was proposed to confirm the effectiveness of ERK1/2 involved in UVB-induced immunosuppression that was reversed by PD. METHODS: Based on the mouse model of local UVB-induced immunosuppression [UVB exposure, followed by sensitization with dinitrofluorobenzene (DNFB) on the abdomen skin before challenge on the ear site], the PD was applied on the abdomen-irradiated area 1 h, immediately before and 6 h after UVB exposure, respectively. The baseline of ear thickness was measured and remeasured 24 h after the challenge of DNFB for evaluation of ear-swelling response. Histopathologically, the ear biopsies were taken for hematoxylin and eosin staining. RESULTS: Mice that received PD post-irradiation treatment showed a statistically significant contact hypersensitivity compared with the UVB-irradiated mice (P<0.05), and paralleled with the biopsy showing a thickened epidermis with lymphocyte infiltration. Thus, the PD had abrogated the UV-induced local suppression of contact hypersensitivity. CONCLUSION: The ERK1/2 mitogen-activated protein kinase (MAPK) pathway plays an important role in the local UVB-induced immunosuppression, and its specific inhibitor PD can arrest its function, resulting in protection against UVB-induced immunosuppression in the present in vivo study.