Rural Hospital Performance in Guideline-Recommended Ischemic Stroke Thrombolysis, Secondary Prevention, and Outcomes.

BACKGROUND: Existing data suggested a rural-urban disparity in thrombolytic utilization for ischemic stroke. Here, we examined the use of guideline-recommended stroke care and outcomes in rural hospitals to identify targets for improvement. METHODS: This retrospective cohort study included patients (aged ≥18 years) treated for acute ischemic stroke at Get With The Guidelines-Stroke hospitals from 2017 to 2019. Multivariable mixed-effect logistic regression was used to compare thrombolysis rates, speed of treatment, secondary stroke prevention metrics, and outcomes after adjusting for patient- and hospital-level characteristics and stroke severity. RESULTS: Among the 1 127 607 patients admitted to Get With The Guidelines-Stroke hospitals in 2017 to 2019, 692 839 patients met the inclusion criteria. Patients who presented within 4.5 hours were less likely to receive thrombolysis in rural stroke centers compared with urban stroke centers (31.7% versus 43.5%; adjusted odds ratio [aOR], 0.72 [95% CI, 0.68-0.76]) but exceeded rural nonstroke centers (22.1%; aOR, 1.26 [95% CI, 1.15-1.37]). Rural stroke centers were less likely than urban stroke centers to achieve door-to-needle times of ≤45 minutes (33% versus 44.7%; aOR, 0.86 [95% CI, 0.76-0.96]) but more likely than rural nonstroke centers (aOR, 1.24 [95% CI, 1.04-1.49]). For secondary stroke prevention metrics, rural stroke centers were comparable to urban stroke centers but exceeded rural nonstroke centers (aOR of 1.66, 1.94, 2.44, 1.5, and 1.72, for antithrombotics within 48 hours of admission, antithrombotics at discharge, anticoagulation for atrial fibrillation/flutter, statin treatment, and smoking cessation, respectively). In-hospital mortality was similar between rural and urban stroke centers (aOR, 1.11 [95% CI, 0.99-1.24]) or nonstroke centers (aOR, 1.00 [95% CI, 0.84-1.18]). CONCLUSIONS: Rural hospitals had lower thrombolysis utilization and slower treatment times than urban hospitals. Rural stroke centers provided comparable secondary stroke prevention treatment to urban stroke centers and exceeded rural nonstroke centers. These results reveal important opportunities and specific targets for rural health equity interventions.

In acute ICH, minimally invasive surgery improved functional outcome at 180 d.

SOURCE CITATION: Pradilla G, Ratcliff JJ, Hall AJ, et al; ENRICH trial investigators. Trial of early minimally invasive removal of intracerebral hemorrhage. N Engl J Med. 2024;390:1277-1289. 38598795.

Cerebral Microbleeds in Critically Ill Patients with Respiratory Failure or Sepsis: A Scoping Review.

BACKGROUND: Cerebral microbleeds (CMBs) have been described in critically ill patients with respiratory failure, acute respiratory distress syndrome (ARDS), or sepsis. This scoping review aimed to systematically summarize existing literature on critical illness-associated CMBs. METHODS: Studies reporting on adults admitted to the intensive care unit for respiratory failure, ARDS, or sepsis with evidence of CMBs on magnetic resonance imaging were included for review following a systematic search across five databases (MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, and Web of Science) and a two-stage screening process. Studies were excluded if patients' CMBs were clearly explained by another process of neurological injury. RESULTS: Forty-eight studies reporting on 216 critically ill patients (mean age 57.9, 18.4% female) with CMBs were included. Of 216, 197 (91.2%) patients developed respiratory failure or ARDS, five (2.3%) patients developed sepsis, and 14 (6.5%) patients developed both respiratory failure and sepsis. Of 211 patients with respiratory failure, 160 (75.8%) patients had coronavirus disease 2019. The prevalence of CMBs among critically ill patients with respiratory failure or ARDS was 30.0% (111 of 370 patients in cohort studies). The corpus callosum and juxtacortical area were the most frequently involved sites for CMBs (64.8% and 41.7% of all 216 patients, respectively). Functional outcomes were only reported in 48 patients, among whom 31 (64.6%) were independent at discharge, four (8.3%) were dependent at discharge, and 13 (27.1%) did not survive until discharge. Cognitive outcomes were only reported in 11 of 216 patients (5.1%), all of whom showed cognitive deficits (nine patients with executive dysfunction and two patients with memory deficits). CONCLUSIONS: Cerebral microbleeds are commonly reported in patients with critical illness due to respiratory failure, ARDS, or sepsis. CMBs had a predilection for the corpus callosum and juxtacortical area, which may be specific to critical illness-associated CMBs. Functional and cognitive outcomes of these lesions are largely unknown.

NeRF-In: Free-Form Inpainting for Pretrained NeRF With RGB-D Priors.

Neural radiance field (NeRF) has emerged as a versatile scene representation. However, it is still unintuitive to edit a pretrained NeRF because the network parameters and the scene appearance are often not explicitly associated. In this article, we introduce the first framework that enables users to retouch undesired regions in a pretrained NeRF scene without accessing any training data and category-specific data prior. The user first draws a free-form mask to specify a region containing the unwanted objects over an arbitrary rendered view from the pretrained NeRF. Our framework transfers the user-drawn mask to other rendered views and estimates guiding color and depth images within transferred masked regions. Next, we formulate an optimization problem that jointly inpaints the image content in all masked regions by updating NeRF's parameters. We demonstrate our framework on diverse scenes and show it obtained visually plausible and structurally consistent results using less user manual efforts.

Risk of type 2 diabetes after diagnosed gestational diabetes is enhanced by exposure to PM2.5.

BACKGROUND: Air pollution and gestational diabetes mellitus (GDM) are both associated with increased diabetes mellitus (DM) occurrence. However, whether air pollutants modify the effects of GDM on the occurrence of DM has been unknown. This study aims to determine whether the effect of GDM on DM development can be modified by exposure to ambient air pollutants. METHODS: Women with one singleton birth delivery during 2004-14 according to the Taiwan Birth Certificate Database (TBCD) were included as the study cohort. Those newly diagnosed as having DM 1 year or later after childbirth were identified as DM cases. Controls were selected among women without DM diagnosis during follow-up. Personal residence was geocoded and linked with interpolated concentrations of air pollutants into township levels. Conditional logistic regression was used to determine the odds ratio (OR) of pollutant exposure and GDM, adjusting for age, smoking and meteorological variables. RESULTS: There were 9846 women who were newly diagnosed as having DM over a mean follow-up period of 10.2 years. We involved them and the 10-fold matching controls involved in our final analysis. The OR (odds ratio) (95% confidence interval, 95% CI) of DM occurrence per interquartile range increased in particulate matter (PM) smaller than or equal to 2.5 µm (PM2.5) and ozone (O3) was 1.31 (1.22-1.41) and 1.20 (1.16-1.25), respectively. The effects of PM exposure on DM development were significantly higher in the GDM group (OR: 2.46, 95% CI: 1.84-3.30) than in the non-GDM group (OR: 1.30, 95% CI: 1.21-1.40). CONCLUSIONS: Exposure to high levels of PM2.5 and O3 elevates the risk of DM. GDM acted synergistically in DM development with exposure to PM2.5 but not with that to O3.

Truncating PICK1 Variant Identified in Azoospermia Affected Mitochondrial Dysfunction in Knockout Mice.

OBJECTIVE: The protein interacting with C kinase 1 (PICK1) plays a critical role in vesicle trafficking, and its deficiency in sperm cells results in abnormal vesicle trafficking from Golgi to acrosome, which eventually disrupts acrosome formation and leads to male infertility. METHODS: An azoospermia sample was filtered, and the laboratory detection and clinical phenotype indicated typical azoospermia in the patient. We sequenced all of the exons in the PICK1 gene and found that there was a novel homozygous variant in the PICK1 gene, c.364delA (p.Lys122SerfsX8), and this protein structure truncating variant seriously affected the biological function. Then we constructed a PICK1 knockout mouse model using clustered regularly interspaced short palindromic repeat cutting technology (CRISPRc). RESULTS: The sperm from PICK1 knockout mice showed acrosome and nucleus abnormalities, as well as dysfunctional mitochondrial sheath formation. Both the total sperm and motility sperm counts were decreased in the PICK1 knockout mice compared to wild-type mice. Moreover, the mitochondrial dysfunction was verified in the mice. These defects in the male PICK1 knockout mice may have eventually led to complete infertility. CONCLUSION: The c.364delA novel variant in the PICK1 gene associated with clinical infertility, and pathogenic variants in the PICK1 may cause azoospermia or asthenospermia by impairing mitochondrial function in both mice and humans.

Effects of delay to stroke unit admission in patients with ischemic and hemorrhagic stroke.

OBJECTIVE: To determine the association between delay in transfer to a central stroke unit from peripheral institutions and outcomes. METHODS: We conducted a retrospective cohort study of all patients with acute stroke, admitted to a comprehensive stroke center (CSC) from three emergency departments (EDs), between 2016 and 2018. The primary outcomes were length of stay, functional status at 3 months, discharge destination, and time to stroke investigations. RESULTS: One thousand four hundred thirty-five patients were included, with a mean age of 72.9 years, and 92.4% ischemic stroke; 663 (46.2%) patients were female. Each additional day of delay was associated with 2.0 days of increase in length of stay (95% confidence interval [CI] 0.8-3.2, p = 0.001), 11.5 h of delay to vascular imaging (95% CI 9.6-13.4, p < 0.0001), 24.2 h of delay to Holter monitoring (95% CI 7.9-40.6, p = 0.004), and reduced odds of nondisabled functional status at 3 months (odds ratio 0.98, 95% CI 0.96-1.00, p = 0.01). Factors affecting delay included stroke onset within 6 h of ED arrival (605.9 min decrease in delay, 95% CI 407.9-803.9, p < 0.0001), delay to brain imaging (59.4 min increase in delay for each additional hour, 95% CI 48.0-71.4, p < 0.0001), admission from an alternative service (3918.7 min increase in delay, 95% CI 3621.2-4079.9, p < 0.0001), and transfer from a primary stroke center (PSC; 740.2 min increase in delay, 95% CI 456.2-1019.9, p < 0.0001). CONCLUSION: Delay to stroke unit admission in a system involving transfer from PSCs to a CSC was associated with longer hospital stay and poorer functional outcomes.

Wumei pills attenuates 5-fluorouracil-induced intestinal mucositis through Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB pathway and microbiota regulation.

BACKGROUND: Radiotherapy and chemotherapy can kill tumor cells and improve the survival rate of cancer patients. However, they can also damage normal cells and cause serious intestinal toxicity, leading to gastrointestinal mucositis[1]. Traditional Chinese medicine is effective in improving the side effects of chemotherapy. Wumei pills (WMP) was originally documented in the Treatise on Exogenous Febrile Diseases. It has a significant effect on chronic diarrhea and other gastrointestinal diseases, but it is not clear whether it affects chemotherapy-induced intestinal mucositis (CIM). AIM: To explore the potential mechanism of WMP in the treatment of CIM through experimental research. METHODS: We used an intraperitoneal injection of 5-fluorouracil (5-Fu) to establish a CIM mouse model and an oral gavage of WMP decoction (11325 and 22650 mg/kg) to evaluate the efficacy of WMP in CIM. We evaluated the effect of WMP on CIM by observing the general conditions of the mice (body weight, food intake, spleen weight, diarrhea score, and hematoxylin and eosin stained tissues). The expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1ß, and myeloperoxidase (MPO), as well as the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB (TLR4/MyD88/NF-κB) signaling pathway proteins and tight junction proteins (zonula occludens-1, claudin-1, E-cadherin, and mucin-2) was determined. Furthermore, intestinal permeability, intestinal flora, and the levels of short-chain fatty acids (SCFA) were also assessed. RESULTS: WMP effectively improved the body weight, spleen weight, food intake, diarrhea score, and inflammatory status of the mice with intestinal mucositis, which preliminarily confirmed the efficacy of WMP in CIM. Further experiments showed that in addition to reducing the levels of TNF-α, IL-1ß, IL-6, and MPO and inhibiting the expression of the TLR4/MyD88/NF-κB pathway proteins, WMP also repaired the integrity of the mucosal barrier of mice, regulated the intestinal flora, and increased the levels of SCFA (such as butyric acid). CONCLUSION: WMP can play a therapeutic role in CIM by alleviating inflammation, restoring the mucosal barrier, and regulating gut microbiota.

FrictShoes: Providing Multilevel Nonuniform Friction Feedback on Shoes in VR.

Many haptic feedback methods have been proposed to enhance realism in virtual reality (VR). However, friction on the feet in VR, which renders feedback as if walking on different terrains or ground textures or stepping on objects is still less explored. Herein, we propose a wearable device, FrictShoes a pair of foot accessories, to provide multilevel nonuniform friction feedback to feet. This is achieved by the independent functioning of six brakes on six wheels underneath each FrictShoe, which allows the friction levels of the wheels from each to be either matched or to vary. We conducted a magnitude estimation study to understand users' distinguishability of friction force magnitudes (or levels). Based on the results, we performed an exploratory study to realize how users adjust and map the multilevel nonuniform friction patterns to common VR terrains or ground textures. Finally, a VR experience study was conducted to evaluate the performance of the proposed multilevel nonuniform friction feedback to the feet in VR experiences.

ClipGen: A Deep Generative Model for Clipart Vectorization and Synthesis.

This article presents a novel deep learning-based approach for automatically vectorizing and synthesizing the clipart of man-made objects. Given a raster clipart image and its corresponding object category (e.g., airplanes), the proposed method sequentially generates new layers, each of which is composed of a new closed path filled with a single color. The final result is obtained by compositing all layers together into a vector clipart image that falls into the target category. The proposed approach is based on an iterative generative model that (i) decides whether to continue synthesizing a new layer and (ii) determines the geometry and appearance of the new layer. We formulated a joint loss function for training our generative model, including the shape similarity, symmetry, and local curve smoothness losses, as well as vector graphics rendering accuracy loss for synthesizing clipart recognizable by humans. We also introduced a collection of man-made object clipart, ClipNet, which is composed of closed-path layers, and two designed preprocessing tasks to clean up and enrich the original raw clipart. To validate the proposed approach, we conducted several experiments and demonstrated its ability to vectorize and synthesize various clipart categories. We envision that our generative model can facilitate efficient and intuitive clipart designs for novice users and graphic designers.

Differential Mortality Risks Associated With PM2.5 Components: A Multi-Country, Multi-City Study.

BACKGROUND: The association between fine particulate matter (PM2.5) and mortality widely differs between as well as within countries. Differences in PM2.5 composition can play a role in modifying the effect estimates, but there is little evidence about which components have higher impacts on mortality. METHODS: We applied a 2-stage analysis on data collected from 210 locations in 16 countries. In the first stage, we estimated location-specific relative risks (RR) for mortality associated with daily total PM2.5 through time series regression analysis. We then pooled these estimates in a meta-regression model that included city-specific logratio-transformed proportions of seven PM2.5 components as well as meta-predictors derived from city-specific socio-economic and environmental indicators. RESULTS: We found associations between RR and several PM2.5 components. Increasing the ammonium (NH4+) proportion from 1% to 22%, while keeping a relative average proportion of other components, increased the RR from 1.0063 (95% confidence interval [95% CI] = 1.0030, 1.0097) to 1.0102 (95% CI = 1.0070, 1.0135). Conversely, an increase in nitrate (NO3-) from 1% to 71% resulted in a reduced RR, from 1.0100 (95% CI = 1.0067, 1.0133) to 1.0037 (95% CI = 0.9998, 1.0077). Differences in composition explained a substantial part of the heterogeneity in PM2.5 risk. CONCLUSIONS: These findings contribute to the identification of more hazardous emission sources. Further work is needed to understand the health impacts of PM2.5 components and sources given the overlapping sources and correlations among many components.

Ambient carbon monoxide and daily mortality: a global time-series study in 337 cities.

BACKGROUND: Epidemiological evidence on short-term association between ambient carbon monoxide (CO) and mortality is inconclusive and limited to single cities, regions, or countries. Generalisation of results from previous studies is hindered by potential publication bias and different modelling approaches. We therefore assessed the association between short-term exposure to ambient CO and daily mortality in a multicity, multicountry setting. METHODS: We collected daily data on air pollution, meteorology, and total mortality from 337 cities in 18 countries or regions, covering various periods from 1979 to 2016. All included cities had at least 2 years of both CO and mortality data. We estimated city-specific associations using confounder-adjusted generalised additive models with a quasi-Poisson distribution, and then pooled the estimates, accounting for their statistical uncertainty, using a random-effects multilevel meta-analytical model. We also assessed the overall shape of the exposure-response curve and evaluated the possibility of a threshold below which health is not affected. FINDINGS: Overall, a 1 mg/m3 increase in the average CO concentration of the previous day was associated with a 0·91% (95% CI 0·32-1·50) increase in daily total mortality. The pooled exposure-response curve showed a continuously elevated mortality risk with increasing CO concentrations, suggesting no threshold. The exposure-response curve was steeper at daily CO levels lower than 1 mg/m3, indicating greater risk of mortality per increment in CO exposure, and persisted at daily concentrations as low as 0·6 mg/m3 or less. The association remained similar after adjustment for ozone but was attenuated after adjustment for particulate matter or sulphur dioxide, or even reduced to null after adjustment for nitrogen dioxide. INTERPRETATION: This international study is by far the largest epidemiological investigation on short-term CO-related mortality. We found significant associations between ambient CO and daily mortality, even at levels well below current air quality guidelines. Further studies are warranted to disentangle its independent effect from other traffic-related pollutants. FUNDING: EU Horizon 2020, UK Medical Research Council, and Natural Environment Research Council.

Acute carotid stenting in patients undergoing thrombectomy: a systematic review and meta-analysis.

BACKGROUND: The benefit of acute carotid stenting compared with no acute stenting on clinical outcomes among patients with tandem lesions (TL) undergoing endovascular thrombectomy (EVT) remains unknown. METHODS: We conducted a a systematic review and meta-analysis of studies comparing acute carotid stenting versus no stenting among TL patients undergoing EVT with regards to 90 day modified Rankin Scale (mRS) score, symptomatic intracerebral hemorrhage (sICH), and mortality. Four reviewers screened citations for eligibility and two assessed retained studies for risk of bias and data extraction. A random effects model was used for the synthesis of aggregated data. RESULTS: 21 studies (n=1635 patients) were identified for the systematic review; 19 were cohort studies, 1 was a post-hoc analysis of an EVT trial, and 1 was a pilot randomized controlled trial. 16 studies were included in the meta-analysis. Acute stenting was associated with a favorable 90 day mRS score: OR 1.43 (95% CI 1.07, 1.91). No significant heterogeneity between studies was found for this outcome (I2=17.0%; χ2=18.07, p=0.26). There were no statistically significant differences for 3 month mortality (OR 0.80 (95% CI 0.50, 1.28)) or sICH (OR 1.41 (95% CI 0.91, 2.19)). CONCLUSIONS: This meta-analysis suggests that among TL patients undergoing EVT, acute carotid stenting is associated with a greater likelihood of favorable outcome at 90 days compared with no stenting.

Projections of excess mortality related to diurnal temperature range under climate change scenarios: a multi-country modelling study.

BACKGROUND: Various retrospective studies have reported on the increase of mortality risk due to higher diurnal temperature range (DTR). This study projects the effect of DTR on future mortality across 445 communities in 20 countries and regions. METHODS: DTR-related mortality risk was estimated on the basis of the historical daily time-series of mortality and weather factors from Jan 1, 1985, to Dec 31, 2015, with data for 445 communities across 20 countries and regions, from the Multi-Country Multi-City Collaborative Research Network. We obtained daily projected temperature series associated with four climate change scenarios, using the four representative concentration pathways (RCPs) described by the Intergovernmental Panel on Climate Change, from the lowest to the highest emission scenarios (RCP 2.6, RCP 4.5, RCP 6.0, and RCP 8.5). Excess deaths attributable to the DTR during the current (1985-2015) and future (2020-99) periods were projected using daily DTR series under the four scenarios. Future excess deaths were calculated on the basis of assumptions that warmer long-term average temperatures affect or do not affect the DTR-related mortality risk. FINDINGS: The time-series analyses results showed that DTR was associated with excess mortality. Under the unmitigated climate change scenario (RCP 8.5), the future average DTR is projected to increase in most countries and regions (by -0·4 to 1·6°C), particularly in the USA, south-central Europe, Mexico, and South Africa. The excess deaths currently attributable to DTR were estimated to be 0·2-7·4%. Furthermore, the DTR-related mortality risk increased as the long-term average temperature increased; in the linear mixed model with the assumption of an interactive effect with long-term average temperature, we estimated 0·05% additional DTR mortality risk per 1°C increase in average temperature. Based on the interaction with long-term average temperature, the DTR-related excess deaths are projected to increase in all countries or regions by 1·4-10·3% in 2090-99. INTERPRETATION: This study suggests that globally, DTR-related excess mortality might increase under climate change, and this increasing pattern is likely to vary between countries and regions. Considering climatic changes, our findings could contribute to public health interventions aimed at reducing the impact of DTR on human health. FUNDING: Korea Ministry of Environment.

Ambient air pollution and asthma onset in Taiwanese adults.

BACKGROUND: Ambient nitrogen dioxide is associated with asthma occurrence in adults in Western countries. However, two recent large-scale studies have provided inconclusive results regarding this association. Moreover, the association remains unknown in an Asian population. OBJECTIVE: We aimed to investigate the association between ambient air pollution exposure and incident adult asthma. METHODS: From 2016 to 2017, we conducted a cross-sectional self-administered questionnaire survey with retrospective follow-up of incident asthma cases among schoolchildren's parents from 41 schools within 1 km of air monitoring stations distributed throughout the main island of Taiwan. To estimate participants' exposure, air pollution data of air monitoring stations within 1 km of schools from where participants were sampled were inputted into the proximity model. We used mixed logistic regression models to determine the association between air pollution exposure and asthma onset within five years prior to the survey. RESULTS: The questionnaire was completed for a total of 11 585 participants out of 13 424 candidates (response rate, 86.3%). Among 9131 participants aged from 26 to 50 years, 101 were diagnosed with asthma within the five years prior to the survey. The prevalence of incident asthma cases was 2.2 per 1000 person-years. Those exposed to higher ambient nitrogen dioxide (odds ratio = 1.20 per interquartile [5.7 ppb] of nitrogen dioxide, 95% CI = 1.02-1.42) were more likely to develop adult-onset asthma. CONCLUSION: In an Asian population, exposure to higher ambient nitrogen dioxide is associated with increased prevalence of incident asthma cases among adults aged 26-50 years.

Association of age-related macular degeneration on fracture risks among osteoporosis population: a nationwide population-based cohort study.

OBJECTIVES: Visual impairment is an important risk factor for fracture in the elderly population. Age-related macular degeneration (AMD) is the leading cause of irreversible visual impairment in elderly people. This study was conducted to explore the relationship between AMD and incident fractures in patients with osteoporosis (OS). DESIGN: Retrospective analysis of Taiwan's National Health Insurance Research Database (NHIRD). SETTING: A multicenter study conducted in Taiwan. PARTICIPANTS AND CONTROLS: The current study used the NHIRD in Taiwan between 1996 and 2011. A total of 13 584 and 54 336 patients with OS were enrolled in the AMD group and the non-AMD group, respectively. INTERVENTION: Patients with OS were included from the Taiwan's NHIRD after exclusion, and each patient with AMD was matched for age, sex and comorbidities to four patients with non-AMD OS, who served as the control group. A Cox proportional hazard model was used for the multivariable analysis. PRIMARY OUTCOME MEASURES: Transitions for OS to spine fracture, OS to hip fracture, OS to humero-radio-ulnar fracture and OS to death. RESULTS: The risks of spine and hip fractures were significantly higher in the AMD group (HR=1.09, 95% CI=1.04 to 1.15, p<0.001; HR=1.18; 95% CI=1.08 to 1.30, p=0.001, respectively) than in the non-AMD group. The incidence of humero-radio-ulnar fracture between AMD and non-AMD individuals was similar (HR=0.98; 95% CI=0.90 to 1.06; p=0.599). However, the risk of death was higher in patients with OS with older age, male sex and all types of comorbidity (p<0.05), except for hyperthyroidism (p=0.200). CONCLUSION: Patients with OS with AMD had a greater risk of spine and hip fractures than did patients without AMD.

[Effect of nanostructured lipid carriers (NLCs) in improving stability of essential oils and its application].

Essential oils are easy to cause oxidative damage, chemical transformation or polymerization, and have some intrinsic problems, such as instability, low water solubility and low bioavailability, which restrict their application in the fields of product development. Nanostructured lipid carriers(NLCs) can overcome some of the restrictions of other colloidal carriers, such as emulsions, liposomes, polymer nanoparticles and solid lipid nanoparticles. NLC is an efficient and stable delivery system for bioactive substances. With unique lipid properties(mixture of solid and liquid lipid), it can overcome the disadvantages of essential oils and protect them from adverse environments, thus improving the stability, bioavailability and safety of essential oils, and achieve sustained release and controlled release. In EOs-NLCs system, essential oils, as special liquid lipid with biological activities and medicinal properties, can fully play the role of medicine-adjuvant integration by changing the structural characteristics of mixed lipid. Based on the development of nanocarriers system, this paper introduces the composition and structural characteristics of EOs-NLCs, and clarifies how to improve the stability of essential oils based on the effects of NLCs on physical and chemical properties, physical stability and release of active components of essential oils. In addition, it also introduces the application of the system in the fields of pharmaceutical, food, cosmetics and skin care products. This review aims to provide some references for improving the stability of essential oils and their applications by using NLCs.

Second-line Hormonal Therapy for the Management of Metastatic Castration-resistant Prostate Cancer: a Real-World Data Study Using a Claims Database.

We evaluated the efficacy of second-line hormonal therapy for treatment of metastatic castration-resistant prostate cancer (mCRPC) in a real-world retrospective study. We conducted a population-based real-world cohort study of 258 mCRPC patients between 2014 and 2018 using the Chang Gung Research Database (CGRD) of Taiwan. The second-line hormonal therapy included abiraterone acetate and enzalutamide. The clinical efficacy outcomes were overall survival (OS) and prostate-specific antigen (PSA) doubling time. The median PSA level was also assessed. In total, 223 mCRPC patients who underwent second-line hormonal therapy met all of the inclusion and exclusion criteria for this study. Among them, 65 (29.1%) patients were in the PSA response group and 158 (70.9%) were in the non-response group. The median age was 72.9 years. The median OS was 12.3 months (range: 9.9-19.9 months) and 9.6 months (range: 5.3-15.9 months) in the response and non-response groups, respectively, and the respective PSA doubling times were 9.0 months (range: 4.4-11.6 months) and 3.9 months (range: 2.2-9.1 months), with a median follow-up period of 10.5 months. A significantly longer median OS was seen in the PSA response group. This real-world database study demonstrated that clinical outcomes of second-line hormonal therapy were better in patients with a PSA response. Further studies are warranted to achieve a better understanding of second-line hormonal therapy for mCRPC in Asian populations.

Short term association between ozone and mortality: global two stage time series study in 406 locations in 20 countries.

OBJECTIVE: To assess short term mortality risks and excess mortality associated with exposure to ozone in several cities worldwide. DESIGN: Two stage time series analysis. SETTING: 406 cities in 20 countries, with overlapping periods between 1985 and 2015, collected from the database of Multi-City Multi-Country Collaborative Research Network. POPULATION: Deaths for all causes or for external causes only registered in each city within the study period. MAIN OUTCOME MEASURES: Daily total mortality (all or non-external causes only). RESULTS: A total of 45 165 171 deaths were analysed in the 406 cities. On average, a 10 µg/m3 increase in ozone during the current and previous day was associated with an overall relative risk of mortality of 1.0018 (95% confidence interval 1.0012 to 1.0024). Some heterogeneity was found across countries, with estimates ranging from greater than 1.0020 in the United Kingdom, South Africa, Estonia, and Canada to less than 1.0008 in Mexico and Spain. Short term excess mortality in association with exposure to ozone higher than maximum background levels (70 µg/m3) was 0.26% (95% confidence interval 0.24% to 0.28%), corresponding to 8203 annual excess deaths (95% confidence interval 3525 to 12 840) across the 406 cities studied. The excess remained at 0.20% (0.18% to 0.22%) when restricting to days above the WHO guideline (100 µg/m3), corresponding to 6262 annual excess deaths (1413 to 11 065). Above more lenient thresholds for air quality standards in Europe, America, and China, excess mortality was 0.14%, 0.09%, and 0.05%, respectively. CONCLUSIONS: Results suggest that ozone related mortality could be potentially reduced under stricter air quality standards. These findings have relevance for the implementation of efficient clean air interventions and mitigation strategies designed within national and international climate policies.

Periconceptional exposure to air pollution and congenital hypospadias among full-term infants.

BACKGROUND: Evidence regarding whether prenatal exposure to air pollution increases the risk of hypospadias remains limited. The aim of the study is to evaluate the association between exposure to ambient air pollution during early pregnancy and the incidence of hypospadias. METHODS: We conducted a 1:10 case-control study using the Taiwanese Birth Registry database. Male full-term infants reported to have hypospadias were defined as cases, and controls were randomly selected from male full-term infants without any congenital anomaly. The monthly average of ambient air pollutants, including PM10, PM2.5, PM2.5-10, NO2, NOx, O3, and O3 8-h maximum, from 3 months before conception to 6 months post conception was retrieved from air quality monitoring stations and interpolated to the level of township using the kriging method. Multivariable logistic regression models were utilized to evaluate the associations. RESULTS: A total of 200 hypospadias cases, with 2000 healthy controls sampled, were reported during 2007-2014. The results revealed that PM2.5 exposure during the first 3 months after conception (odds ratio [OR] = 1.29, 95% confidence interval [CI]: 1.01-1.65, per interquartile range [IQR] = 15.6 µg/m3) and O3 exposure during the first month after conception (OR = 1.40, 95% CI: 1.08-1.82, per IQR = 8.0 ppb) were associated with a higher incidence of hypospadias. CONCLUSIONS: The results of the study suggest that early gestational exposure to ambient air pollution increases the risk of hypospadias among full-term infants.