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.

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.

Ambient Particulate Air Pollution and Daily Mortality in 652 Cities.

BACKGROUND: The systematic evaluation of the results of time-series studies of air pollution is challenged by differences in model specification and publication bias. METHODS: We evaluated the associations of inhalable particulate matter (PM) with an aerodynamic diameter of 10 µm or less (PM10) and fine PM with an aerodynamic diameter of 2.5 µm or less (PM2.5) with daily all-cause, cardiovascular, and respiratory mortality across multiple countries or regions. Daily data on mortality and air pollution were collected from 652 cities in 24 countries or regions. We used overdispersed generalized additive models with random-effects meta-analysis to investigate the associations. Two-pollutant models were fitted to test the robustness of the associations. Concentration-response curves from each city were pooled to allow global estimates to be derived. RESULTS: On average, an increase of 10 µg per cubic meter in the 2-day moving average of PM10 concentration, which represents the average over the current and previous day, was associated with increases of 0.44% (95% confidence interval [CI], 0.39 to 0.50) in daily all-cause mortality, 0.36% (95% CI, 0.30 to 0.43) in daily cardiovascular mortality, and 0.47% (95% CI, 0.35 to 0.58) in daily respiratory mortality. The corresponding increases in daily mortality for the same change in PM2.5 concentration were 0.68% (95% CI, 0.59 to 0.77), 0.55% (95% CI, 0.45 to 0.66), and 0.74% (95% CI, 0.53 to 0.95). These associations remained significant after adjustment for gaseous pollutants. Associations were stronger in locations with lower annual mean PM concentrations and higher annual mean temperatures. The pooled concentration-response curves showed a consistent increase in daily mortality with increasing PM concentration, with steeper slopes at lower PM concentrations. CONCLUSIONS: Our data show independent associations between short-term exposure to PM10 and PM2.5 and daily all-cause, cardiovascular, and respiratory mortality in more than 600 cities across the globe. These data reinforce the evidence of a link between mortality and PM concentration established in regional and local studies. (Funded by the National Natural Science Foundation of China and others.).

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.

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.

Association between air pollution exposure and diabetic retinopathy among diabetics.

BACKGROUND: Exposure to air pollution has been linked to adverse effects on vascular diseases. However, the effects of air pollution exposure on diabetic retinopathy (DR), a vascular disease, have not been studied. OBJECTIVE: To determine the association of ambient air pollution exposure with DR risk. METHODS: Patients newly diagnosed as having diabetes mellitus (DM) during 2003-2012 from Longitudinal Health Insurance Database 2005), a subset of National Health Insurance Research Database, were included as the study cohort. Newly diagnosed DR patients one year or later after DM diagnosis were identified as cases. Kriging was used to interpolate yearly concentrations of air pollutants at township levels and linked with every individual's residence in each year; average concentrations during the follow-up period were then calculated as personal exposure. Conditional logistic regressions with adjustments for age at DM diagnosis and comorbidities were applied. RESULTS: Of newly diagnosed DM cases during 2003-2012, 579 were newly diagnosed as having DR over a mean follow-up period of 5.6 years. The Odds ratio (95% confidence interval) of DR occurrence for every 10-µg/m3 increase in particulate matter with ≤2.5 and 2.5-10-µm diameter was 1.29 (1.11-1.50) and 1.37 (1.17-1.61), respectively. CONCLUSION: In patients with DM, the higher particulate matter exposure, the higher is the DR risk.

[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.

Changes in the relationship between childhood asthma and ambient air pollution in Taiwan: Results from a nationwide survey repeated 5 years apart.

BACKGROUND: Childhood asthma is a common disease whose prevalence is changing. Shift in environmental exposure was one of the plausible explanations. This study investigated changes in the association between childhood asthma and ambient air pollution occurring over time. METHOD: A nationwide questionnaire survey concerning respiratory illness and symptoms was administered to Taiwanese elementary and middle school students in 2011 and repeatedly in 2016-2017. During the study period, the concentrations of ambient air pollutants were obtained from the Environmental Protection Administration (EPA) monitoring stations. Generalized estimating equation models were applied to examine the association between air pollution in the past year and the risk of current asthma. RESULTS: A total of 6346 children from the 2011 survey and 11 585 children from the 2016-2017 survey attended schools located within a 1-km radius of Taiwan EPA monitoring stations. The prevalence of childhood current asthma (children with physician-diagnosed asthma and persistent asthma symptoms in the past year) increased from 7.5% to 9.6% during this period. The level of exposure to particulate matter with an aerodynamic diameter of ≤2.5 µm (PM2.5 ) in the past year was found to be associated with current asthma both in the 2011 survey (odds ratio (OR): 1.90, 95% confidence interval (CI): 1.41-2.57) and in the 2016-2017 survey (OR: 1.24, 95% CI: 1.04-1.48). CONCLUSION: Improved air quality has reduced the effect of PM2.5 on childhood asthma, but air quality remains a health concern in Taiwan.

Significant effects of exposure to relatively low level ozone on daily mortality in 17 cities from three Eastern Asian Countries.

BACKGROUND: Studies have examined the variation in mortality risk associated with ambient ozone. We conducted an international cooperation study for investigating the non-linear ozone-mortality association accounting for lag effect and for examining the ozone level with significant health effect. METHODS: Daily counts of total non-accidental death and ambient air pollutant concentration were obtained in 17 cities from 3 Eastern Asian countries or regions (Taiwan, Korea, and Japan). The total study period was from 1979 to 2010 and differed by city based on data availability. The ozone-mortality association in each city was estimated by running a time-series quasi-Poisson regression model, allowing for overdispersion. The city-specific estimates were then pooled by country by using multivariate random effects meta-analysis. RESULTS: The non-linear ozone exposure-mortality response curves were generated in 17 cities from Taiwan, Korea, and Japan. The association curves in the three countries all showed increased mortality with elevated ozone, and the significant mortality effects of ozone exposure were observed at level higher than 40, 50, and 40 ppb for Taiwan, Korea, and Japan, respectively. These associations are unaffected by co-pollutant of particulate matter in Taiwan and Japan. But the potential confounding effect of co-pollutant could not be ignorable in Korea. CONCLUSIONS: Our study provides evidence that exposure to a relative low level of ambient ozone is associated with an increased risk of mortality. Our results emphasize the continual need to examine the existing standard by documenting potential human adverse effects.

Changes in the relationship between ambient fine particle concentrations and childhood lung function over 5 years.

BACKGROUND: Exposure to ambient fine particles, particulate matter with an aerodynamic diameter of ≤2.5 µm (PM2.5), is a public health concern. Concentrations of ambient PM2.5 have changed temporally in the past 10 years after a series of action policies for improving air quality were implemented in Taiwan. In this study, temporal changes in the relationship between PM2.5 and lung function among children were investigated. METHODS: A nationwide respiratory health survey was conducted among Taiwanese elementary and middle school students in 2011 and again in 2016-2017. A questionnaire was administered to students, for whom forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were measured using spirometry. During the study period, monthly concentrations of ambient PM2.5 were obtained from the monitoring stations of the Environmental Protection Administration. Lung function measurements were compared with ambient PM2.5 exposure using mixed-effects models. RESULTS: In the 2011 survey (mean PM2.5: 40.6 µg/m3), exposure to PM2.5 in the preceding 1-2 months was associated with a 2.2% decrease (95% confidence interval [CI]: -4.1%, -0.3%) in FVC and a 2.3% decrease (95% CI: -4.0%, -0.5%) in FEV1. By contrast, a significant relationship between PM2.5 concentrations and lung function was not observed in the 2016-2017 survey (mean PM2.5: 30.0 µg/m3). CONCLUSIONS: As improvement in air quality over time, the negative relationship between PM2.5 and childhood lung function tend to be not significant.

Atrial fibrillation hospitalization is associated with exposure to fine particulate air pollutants.

BACKGROUND: Although air pollutants have been associated with cardiopulmonary mortality, their effects on the occurrence of atrial fibrillation (Afib) remain unclear. This study examined the association between ambient air pollutants and Afib occurrence. METHODS: Using a representative sample from the National Health Insurance Database of Taiwan, we applied a case-crossover study design to explore the associations between air pollutants and patients hospitalized with Afib from 2006 to 2011. The event day was when a patient was hospitalized with Afib, and the control days were the same days of the following weeks of the same month. The association between Afib occurrence and levels of ambient air pollutants (including particulate matter [PM] 2.5 PM10, NO2, SO2, and O3) was examined after adjusting for temperature and relative humidity. A two-pollutant model was used to examine the effect of the second pollutant when the first pollutant was determined to be significantly related to Afib. RESULTS: During 2006-2011, 670 patients hospitalized with the first onset of Afib were identified. The occurrence of Afib was associated with PM2.5, in which a 22% (95% confidence interval = 3-44%) increase was related to an interquartile range increase (26.2 µg/m3) on the same day and a 19% (95% confidence interval = 0-40%) increase on the second day. A two-pollutant model was applied, and the results indicated that the effect of PM2.5 was significantly associated with the occurrence of Afib. Patients aged over 65 years with DM and with hyperlipidemia were more susceptible to the effect of PM2.5. CONCLUSIONS: In conclusion, the occurrence of Afib was associated with short-term exposure to fine particulate air pollutants in the general population.

Adherence to Guidelines at a Stroke Prevention Clinic: A Follow-up Study.

BACKGROUND: In 2010, we published our stroke prevention clinic's performance as compared to Canadian stroke prevention guidelines. We now compare our clinic's adherence with guidelines to our previous results, following the implementation of an electronic documentation form. METHODS: All new patients referred to our clinic (McGill University Health Center) for recent transient ischemic attack (TIA) or ischemic stroke between 2014 and 2017 were included. We compared adherence to guidelines to our previous report (N=408 patients for period 2008-2010) regarding vascular risk management and treatment. RESULTS: Three hundred and ninety-two patients were included, of which 36% had a TIA and 64% had an ischemic stroke, with a mean age of 70 years and 43% female. Although the more recent cohort has shown a higher proportion of cardioembolic stroke compared to previous (19.1% vs. 14.7%) following new guidelines regarding prolonged cardiac monitoring, increased popularity in CT angiography has not translated into greater proportion of large-artery stroke subtype (26.3% vs. 26.2%). Blood pressure (BP) targets were achieved in 83% compared with 70% in our previous report (p<0.01). Attainment of low-density lipoprotein cholesterol target was also improved in our recent study (66% vs. 46%, p<0.01). No significant difference was found in the consistency of antithrombotic use (97.7% vs. 99.8%, p=0.08). However, there was a decline in smoking cessation (35% vs. 73%, p=0.02). Overall, optimal therapy status was better attained in the present cohort compared to the previous one (52% vs. 22%, p<0.01). The male sex was associated with better attainment of optimal therapy status (odds ratio, 1.61; 95% confidence interval, 1.04-2.51). The number of follow-up visits and the length of follow-up were not associated with attainment of stroke prevention targets. CONCLUSIONS: Our study shows improvement in attainment of therapeutic goals as recommended by Canadian stroke prevention guidelines, possibly attributed in part to the implementation of electronic medical recording in our clinic. Areas for improvement include smoking cessation counseling and diabetes screening.

CONTEXTE: En 2010, nous avons rendu publics les résultats de notre clinique de prévention des AVC en ce qui regarde les lignes directrices canadiennes de prévention des AVC. Suite à la mise en place d'un formulaire d'information électronique, nous voulons maintenant comparer l'adhésion actuelle de notre clinique à ces lignes directrices à celle mesurée en 2010. MÉTHODES: Tous les nouveaux patients adressés à notre clinique (Centre universitaire de santé McGill) pour des cas récents d'ischémie cérébrale transitoire (ICT) ou d'AVC ischémique survenus entre 2014 et 2017 ont été inclus dans cette étude. Nous avons ainsi comparé l'adhésion actuelle aux lignes directrices évoquées ci-haut à celle du précédent rapport (N = 408 patients pour la période allant de 2008 à 2010), et ce, en ce qui concerne la prise en charge du risque vasculaire et les traitements nécessaires. RÉSULTATS: Au total, 392 patients ont été inclus; de ce nombre, 36 % d'entre eux avaient été victimes d'ICT tandis que 64 % avaient été victimes d'un AVC ischémique. Leur âge moyen était de 70 ans et 43 % d'entre eux étaient de sexe féminin. Bien que la cohorte la plus récente, à la suite de l'introduction de nouvelles lignes directrices portant sur la surveillance cardiaque prolongée, ait donné à voir une proportion plus élevée d'AVC d'origine cardio-embolique comparativement à la précédente (19,1 % par opposition à 14,7 %), la popularité croissante de l'angiographie par tomodensitométrie ne s'est pas traduite par une proportion plus grande de sous-types d'AVC affectant de grandes artères (26,3 % de 2014 à 2017 par opposition à 26,2 % de 2008 à 2010). Les valeurs cibles fixées en matière de pression artérielle ont été atteintes dans 83 % des cas comparativement à 70 % des cas dans notre rapport précédent (p < 0,01). L'atteinte de la valeur cible en ce qui concerne le taux de LDL-cholestérol (lipoprotéines de faible intensité) a également été améliorée dans notre plus récent rapport (66 % par opposition à 46 %; p < 0,01). Ajoutons aussi qu'aucune différence notable n'a été observée quant à une utilisation constante d'anti-thrombotiques (97,7 % par opposition à 99,8 %; p = 0,08). Fait à souligner, un déclin dans l'abandon du tabagisme a été noté (35 % par opposition à 73%; p = 0,02). Dans l'ensemble, les conditions d'une guérison optimale (optimal therapy status) ont été davantage atteintes dans la cohorte la plus récente comparativement à celle de 2008 à 2010 (52 % par opposition à 22 %; p < 0,01). Le fait d'être de sexe masculin a été associé à de meilleures conditions de guérison optimale (rapport des cotes: 1,61; IC 95 %, 1,04 ­ 2,51). Enfin, mentionnons que le nombre de consultations de suivi et la durée des suivis n'ont pas été associés à l'atteinte de valeurs cibles en matière de prévention des AVC. CONCLUSIONS: Notre étude montre une série d'améliorations dans l'atteinte des objectifs thérapeutiques recommandés par les lignes directrices canadiennes de prévention des AVC. Cela pourrait être en partie attribuable à la mise en place de dossiers médicaux informatisés au sein de notre clinique. Parmi les aspects qui méritent une amélioration, citons l'établissement d'un programme de counseling en ce qui regarde l'abandon du tabagisme et le dépistage du diabète.

Quantifying excess deaths related to heatwaves under climate change scenarios: A multicountry time series modelling study.

BACKGROUND: Heatwaves are a critical public health problem. There will be an increase in the frequency and severity of heatwaves under changing climate. However, evidence about the impacts of climate change on heatwave-related mortality at a global scale is limited. METHODS AND FINDINGS: We collected historical daily time series of mean temperature and mortality for all causes or nonexternal causes, in periods ranging from January 1, 1984, to December 31, 2015, in 412 communities within 20 countries/regions. We estimated heatwave-mortality associations through a two-stage time series design. Current and future daily mean temperature series were projected under four scenarios of greenhouse gas emissions from 1971-2099, with five general circulation models. We projected excess mortality in relation to heatwaves in the future under each scenario of greenhouse gas emissions, with two assumptions for adaptation (no adaptation and hypothetical adaptation) and three scenarios of population change (high variant, median variant, and low variant). Results show that, if there is no adaptation, heatwave-related excess mortality is expected to increase the most in tropical and subtropical countries/regions (close to the equator), while European countries and the United States will have smaller percent increases in heatwave-related excess mortality. The higher the population variant and the greenhouse gas emissions, the higher the increase of heatwave-related excess mortality in the future. The changes in 2031-2080 compared with 1971-2020 range from approximately 2,000% in Colombia to 150% in Moldova under the highest emission scenario and high-variant population scenario, without any adaptation. If we considered hypothetical adaptation to future climate, under high-variant population scenario and all scenarios of greenhouse gas emissions, the heatwave-related excess mortality is expected to still increase across all the countries/regions except Moldova and Japan. However, the increase would be much smaller than the no adaptation scenario. The simple assumptions with respect to adaptation as follows: no adaptation and hypothetical adaptation results in some uncertainties of projections. CONCLUSIONS: This study provides a comprehensive characterisation of future heatwave-related excess mortality across various regions and under alternative scenarios of greenhouse gas emissions, different assumptions of adaptation, and different scenarios of population change. The projections can help decision makers in planning adaptation and mitigation strategies for climate change.

Visualization of Rostral Migratory Stream in the Developing Rat Brain by In Vivo Electroporation.

Interneurons in the olfactory bulb (OB) are generated from neuronal precursor cells migrating from anterior subventricular zone (SVZa) not only in the developing embryo but also throughout the postnatal life of mammals. In the present study, we established an in vivo electroporation assay to label SVZa cells of rat both at embryonic and postnatal ages, and traced SVZa progenitors and followed their migration pathway and differentiation. We found that labeled cells displayed high motility. Interestingly, the postnatal cells migrated faster than the embryonic cells after applying this assay at different ages of brain development. Furthermore, based on brain slice culture and time-lapse imaging, we analyzed the detail migratory properties of these labeled precursor neurons. Finally, tissue transplantation experiments revealed that cells already migrated in subependymal zone of OB were transplanted back into rostral migratory stream (RMS), and these cells could still migrate out tangentially along RMS to OB. Taken together, these findings provide an in vivo labeling assay to follow and trace migrating cells in the RMS, their maturation and integration into OB neuron network, and unrecognized phenomena that postnatal SVZa progenitor cells with higher motility than embryonic cells, and their migration was affected by extrinsic environments.

Effects of night duty events on blood pressure and autonomic modulation in physicians.

BACKGROUND: The dynamic effects of duty events on the blood pressure (BP) and heart rate variability (HRV) of physicians on duty are unknown. METHODS: A study was conducted among 12 physicians on night duty. BP and HRV with and without the effect of a duty event were compared. The risk of higher BP and impaired HRV after a phone call were calculated. RESULTS: Physicians had higher mean BP (122.4 ± 11.1; 76.9 ± 7.1 mmHg) within 30 min after a phone calls than without a phone call (113.5 ± 5.3; 69.0 ± 3.8) and higher sympathetic tone (low frequency normalized units (LFnu) 68.5 ± 8.9; high frequency normalized units (HFnu) 27.7 ± 8.7) within 10 min of a phone call than without a phone call (62.9 ± 8.51; 33.5 ± 8.4). Elevated BP and sympathetic tone recovered to baseline levels 30 min after a phone call. CONCLUSIONS: Among physicians on night duty, sympathetic tone and BP might be elevated by clinical events, and these effects last for 30 min.

Gestational diabetes mellitus was related to ambient air pollutant nitric oxide during early gestation.

BACKGROUND: Ambient air pollution has been linked to the risk of gestational diabetes mellitus (GDM). However, evidence of this association is limited, and no study has examined the effects of nitric oxide (NO). OBJECTIVE: This study investigated the association between air pollution exposure during gestation and GDM. METHODS: The Taiwan Birth Cohort Study database was used to examine the association between the risk of GDM and all routinely monitored air pollutants among 21,248 women who were pregnant during 2004-2005. We further employed a two-pollutant model for confirming the effect of each pollutant on GDM. RESULTS: After the exclusion criteria were applied, 19,606 women were included in the final analysis. Among them, 378 (1.9%) had been diagnosed as having GDM. These women were older and had higher BMIs than the women without GDM. The risks of GDM onset were significantly associated with NO exposure during the first [adjusted OR (aOR): 1.05, 95% confidence interval (CI): 1.02-1.08] and second (aOR: 1.05, 95%CI: 1.02-1.08) trimesters. Under the two-pollutant model, the effect of NO exposure was also significant during the first (aOR: 1.05, 95%CI: 1.02-1.08) and second (aOR: 1.05, 95%CI: 1.02-1.09) trimesters. CONCLUSION: The results indicated that exposure to higher NO levels during pregnancy increases the risk of GDM.

Short- and Long-Term Reduction of Door-to-Needle Time in Thrombolysis for Acute Stroke.

BACKGROUND: More timely administration of tissue plasminogen activator (alteplase) for patients with acute ischemic stroke yields greater clinical benefits. We implemented door-to-needle (DTN) time reduction strategies at our center and evaluated their short- and long-term effects on in-hospital treatment delays and clinical outcomes. METHODS: Strategies, including stroke team prenotification, direct computed tomography transfer, not routinely waiting for laboratory results and alteplase delivery on the computed tomography table, were implemented in June 2013. We included all thrombolysed patients admitted directly to our hospital between January 2012 and March 2015. In-hospital delays and symptomatic intracerebral hemorrhage rates were compared between patients pre- and postmodification, and the latter period was divided into early (first 6 months) and late (beyond 6 months) phases to assess the durability of our modifications. RESULTS: Forty-eight individuals were treated premodification compared with 58 postmodification. The median DTN time was reduced from 75 to 46 minutes (p<0.0001). The median DTN time in the early and late postmodification phases was not significantly different (41 vs 46 minutes, p=0.4085). There was no significant difference in rates of symptomatic intracerebral hemorrhage (4.2 vs 1.7%, p=0.361) or stroke mimics (2.1 ves 5.2%, p=0.625) Conclusions: We were able to decrease our DTN time for acute stroke thrombolysis by implementing relatively simple modifications and these improvements persisted over time.

Schoolchildren's antioxidation genotypes are susceptible factors for reduced lung function and airway inflammation caused by air pollution.

BACKGROUND: We recently reported the relationship between exposure to ambient air pollutants and changes in lung function and nasal inflammation among schoolchildren. A study was conducted to investigate whether antioxidation genotypes influence these associations. METHODS: A follow-up study of 97 schoolchildren was conducted in New Taipei City, Taiwan. A structured respiratory health questionnaire was administered in September 2007, followed by monthly spirometry and measurement of nasal inflammation from October 2007 to November 2009. During the study period, complete daily monitoring data for air pollutants were obtained from the Environmental Protection Administration monitoring station and Aerosol Supersite. The genotypes of glutathione S-transferase (GST) subunits M1, T1, P1 and superoxide dismutases subunit 2 (SOD2) were characterized. Mixed-effects models were used, adjusting for known confounders. RESULT: GSTM1 null children had significant PM2.5-related increment in leukocyte (8.52%; 95% confidence interval (CI): 3.13-13.92%) and neutrophil (9.68%; 95% CI: 4.51-14.85%) in nasal lavage. Ozone levels were significantly and inversely associated with forced expiratory flow at 25% of forced vital capacity (FEF25%) (-0.43L/s; 95% CI: -0.58,-0.28L/s) in SOD2 Ala16 variant children. CONCLUSION: In this longitudinal study of schoolchildren. Our data provide evidence that antioxidation genotype modifies the airway inflammation caused by PM2.5. Antioxidation genotype also acts as an effect modifier, but not strong, in ozone-related small airway function response.

Age of asthma onset and vulnerability to ambient air pollution: an observational population-based study of adults from Southern Taiwan.

BACKGROUND: Late-onset asthma (onset > 12 years) is pathologically distinct from early-onset asthma. The mechanism of air pollution is not a classic allergic inflammation and could have differential effect on late-onset and early-onset asthma. However, there is little known about the association of onset-age phenotype and air pollution. In this population-based study, we aimed to determine the association of asthma severity outcomes and air pollution regarding age at onset of asthma. METHODS: In 2004, we conducted a cross-sectional questionnaire survey about respiratory health among schoolchildren's parents randomly selected from 94 of 816 elementary and middle schools in southern Taiwan. Participants ever having typical asthma symptoms were enrolled. We used kriging method to estimate individual exposure to ambient air pollution in the preceding year before the year of asthma severity survey. Ordered logistic regression was used to determine the association of exposure and asthma severity scores. Age at asthma onset of 12 years was used as a cut-off to define early- or late-onset asthma. RESULTS: The study surveyed 35,682 participants. Data from 23,551 participants remained satisfactory with a response rate of 66 %. Among 20,508 participants aged 26-50 years, 703 questionnaire-determined asthmatics were identified and included for analysis. Using the median of PM10 (66 µg/m(3)) as a cut-off, those exposed to higher PM10 were more likely to have higher severity scores (OR = 1.74; 95 % CI, 1.13 - 2.70) only for asthmatics with asthma onset at > 12 years. CONCLUSIONS: In adulthood, exposure to PM10 has a greater effect on late-onset asthma than early-onset asthma and deserves greater attention among ambient air pollutants.

Increased night duty loading of physicians caused elevated blood pressure and sympathetic tones in a dose-dependent manner.

PURPOSE: Night duty has been recognized as a significantly harmful stressor for physicians. However, the relationship between various levels of duty loading and stress response is unknown. This study examined whether duty load increases cardiovascular stress indicators in a dose-dependent manner. METHODS: An unallocated prospective observational study was conducted among physicians performing various levels of duties in a secondary referral medical center between 2011 and 2012. Heart rate variability (HRV), blood pressure (BP), and other stress markers of 12 attending physicians were compared during different duty loads: non-duty day (NDD), duty day with one duty area and three wards (1DD), and duty day with two duty areas and six wards (2DD). RESULTS: During the regular sleep time (i.e., 11 p.m. to 5 a.m.), the relative sympathetic modulations measured using the HRV were 59.0 ± 9.3, 61.6 ± 10.4, and 64.4 ± 8.9 for NDD, 1DD, and 2DD, respectively (p = 0.0012); those for relative parasympathetic modulations were 37.4 ± 9.4, 34.8 ± 9.8, and 32.0 ± 8.8 for NDD, 1DD, and 2DD, respectively (p = 0.0015). The percentages of abnormal systolic BPs were 9.7 ± 13.2 %, 25.3 ± 21.8 %, and 31.5 ± 21.0 % for NDD, 1DD, and 2DD, respectively (p = 0.003), and the percentages of abnormal diastolic BP were 6.7 ± 11.0 %, 18.3 ± 11.1 %, and 27.1 ± 30.9 % for NDD, 1DD, and 2DD, respectively (p = 0.002). Total sleep time was negatively associated with sympathetic/parasympathetic balance and the percentage of abnormal diastolic BP. Admitting new patients was positively associated with the percentages of abnormal systolic BP. CONCLUSIONS: This observational analysis suggests that the dose-dependent stress responses of the cardiovascular system in physicians were caused by the duty load.