Trends of hypertensive disorders of pregnancy among the Medicaid population before and during COVID-19.

Hypertensive disorders of pregnancy (HDP) are a group of high blood pressure disorders during pregnancy that are a leading cause of maternal and infant morbidity and mortality. The trend of HDP among the Medicaid population during the coronavirus disease of 2019 (COVID-19) is severely lacking. To determine the trends in the annual prevalence of HDP among Louisiana Medicaid pregnant women before and during the COVID-19 pandemic (2016-2021), a total of 113,776 pregnant women aged 15-50 years was included in this study. For multiparous individuals, only the first pregnancy was used in the analyses. Women with a diagnosis of each type-specific HDP were identified by using the ICD-10 codes. The prevalence of HDP increased from 10.5% in 2016 to 17.7% in 2021. The highest race/ethnicity-specific incidence of HDP was seen in African American women (13.1%), then white women (9.4%), followed by other women (7.9%). HDP remains as a very prevalent and significant global health issue, especially in African American women. Obesity and physical inactivity are major risk factors of HDP, which became amplified during the COVID-19 pandemic and led to a higher prevalence of HDP. Severe HDP substantially increases the risk of mortality in offspring and long-term issues in both the mother and infant. This is very pertinent to the Medicaid population due to the disparities and barriers that diminish the quality of healthcare they receive.

Effect of menopausal hormone therapy on COVID-19 severe outcomes in women - A population-based study of the US National COVID Cohort Collaborative (N3C) data.

Whether menopausal hormone therapy (MHT) lessens the severity of COVID-19 among women is unclear. Leveraging a U.S. national COVID-19 cohort and a cross-sectional analysis, we found MHT use was marginally associated with a lower risk of mortality (odds ratio [OR] 0.73, 95 % CI 0.53-1.01) and significantly associated with a lower risk of prolonged hospital stay (0.7, 0.49-0.99) among inpatient women. When stratifying by MHT type, estrogen-only and estrogen-plus-progestin therapies had a more prominent protective effect than progestin-only therapy, although this difference did not achieve statistical significance. Women with COVID-19 can continue to use MHT. Clinical trials are needed to evaluate MHT's therapeutic effect on COVID-19, especially in terms of severity.

Higher hospitalization and mortality rates among SARS-CoV-2-infected persons in rural America.

PURPOSE: Rural communities are among the most underserved and resource-scarce populations in the United States. However, there are limited data on COVID-19 outcomes in rural America. This study aims to compare hospitalization rates and inpatient mortality among SARS-CoV-2-infected persons stratified by residential rurality. METHODS: This retrospective cohort study from the National COVID Cohort Collaborative (N3C) assesses 1,033,229 patients from 44 US hospital systems diagnosed with SARS-CoV-2 infection between January 2020 and June 2021. Primary outcomes were hospitalization and all-cause inpatient mortality. Secondary outcomes were utilization of supplemental oxygen, invasive mechanical ventilation, vasopressor support, extracorporeal membrane oxygenation, and incidence of major adverse cardiovascular events or hospital readmission. The analytic approach estimates 90-day survival in hospitalized patients and associations between rurality, hospitalization, and inpatient adverse events while controlling for major risk factors using Kaplan-Meier survival estimates and mixed-effects logistic regression. FINDINGS: Of 1,033,229 diagnosed COVID-19 patients included, 186,882 required hospitalization. After adjusting for demographic differences and comorbidities, urban-adjacent and nonurban-adjacent rural dwellers with COVID-19 were more likely to be hospitalized (adjusted odds ratio [aOR] 1.18, 95% confidence interval [CI], 1.16-1.21 and aOR 1.29, CI 1.24-1.1.34) and to die or be transferred to hospice (aOR 1.36, CI 1.29-1.43 and 1.37, CI 1.26-1.50), respectively. All secondary outcomes were more likely among rural patients. CONCLUSIONS: Hospitalization, inpatient mortality, and other adverse outcomes are higher among rural persons with COVID-19, even after adjusting for demographic differences and comorbidities. Further research is needed to understand the factors that drive health disparities in rural populations.

Sex differences in determinants of COVID-19 severe outcomes - findings from the National COVID Cohort Collaborative (N3C).

OBJECTIVE: The impact of comorbidities and biomarkers on COVID-19 severity vary by sex but have not yet been verified in population-based studies. We examined the association of comorbidities, inflammatory biomarkers, and severe outcomes in men and women hospitalized for COVID-19. DESIGN: This is a retrospective cohort analysis based on the National COVID Cohort Collaborative (N3C). We included 574,391 adult patients admitted for COVID-19 at hospitals or emergency rooms between 01/01/2020 and 12/31/2021. METHODS: We defined comorbidities at or before the first admission for COVID-19 by Charlson Comorbidity Index (CCI) and CCI components. We used the averaged lab values taken within 15 days before or after the admission date to measure biomarkers including c-reactive protein (CRP), ferritin, procalcitonin, N-terminal pro b-type natriuretic peptide (NT proBNP), d-dimer, absolute lymphocyte counts, absolute neutrophil counts, and platelets. Our primary outcome was all-cause mortality; secondary outcomes were invasive mechanical ventilation (IMV) and hospital length of stay (LOS). We used logistic regression adjusted for age, race, ethnicity, visit type, and medications to assess the association of comorbidities, biomarkers, and mortality disaggregating by sex. RESULTS: Moderate to severe liver disease, renal disease, metastatic solid tumor, and myocardial infarction were the top four fatal comorbidities among patients who were hospitalized for COVID-19 (adjusted odds ratio [aOR] > 2). These four comorbid conditions remained the most lethal in both sexes, with a higher magnitude of risk in women than in men (p-interaction < 0.05). Abnormal elevations of CRP, ferritin, procalcitonin, NT proBNP, neutrophil, and platelet counts, and lymphocytopenia were significantly associated with the risk of death, with procalcitonin and NT proBNP as the strongest predictors (aOR > 2). The association between the abnormal biomarkers and death was stronger in women than in men (p-interaction < 0.05). CONCLUSION: There are sex differences in inpatient mortality associated with comorbidities and biomarkers. The significant impact of these clinical determinants in women with COVID-19 may be underappreciated as previous studies stressed the increased death rate in male patients that is related to comorbidities or inflammation. Our study highlights the importance and the need for sex-disaggregated research to understand the risk factors of poor outcomes and health disparities in COVID-19.

Association of Obesity and Diabetes With the Incidence of Breast Cancer in Louisiana.

INTRODUCTION: Breast cancer is a heterogeneous disease, consisting of multiple molecular subtypes. Obesity has been associated with an increased risk for postmenopausal breast cancer, but few studies have examined breast cancer subtypes separately. Obesity is often complicated by type 2 diabetes, but the possible association of diabetes with specific breast cancer subtypes remains poorly understood. METHODS: In this retrospective case-control study, Louisiana Tumor Registry records of primary invasive breast cancer diagnosed in 2010-2015 were linked to electronic health records in the Louisiana Public Health Institute's Research Action for Health Network. Controls were selected from Research Action for Health Network and matched to cases by age and race. Conditional logistic regression was used to identify metabolic risk factors. Data analysis was conducted in 2020‒2021. RESULTS: There was a significant association between diabetes and breast cancer for Luminal A, Triple-Negative Breast Cancer, and human epidermal growth factor 2‒positive subtypes. In multiple logistic regression, including both obesity status and diabetes as independent risk factors, Luminal A breast cancer was also associated with overweight status. Diabetes was associated with increased risk for Luminal A and Triple-Negative Breast Cancer in subgroup analyses, including women aged ≥50 years, Black women, and White women. CONCLUSIONS: Although research has identified obesity and diabetes as risk factors for breast cancer, these results underscore that comorbid risk is complex and may differ by molecular subtype. There was a significant association between diabetes and the incidence of Luminal A, Triple-Negative Breast Cancer, and human epidermal growth factor 2‒positive breast cancer in Louisiana.

The Inverse Correlation Between the Duration of Lifetime Occupational Radiation Exposure and the Prevalence of Atrial Arrhythmia.

Objective: Advancements in fluoroscopy-assisted procedures have increased radiation exposure among cardiologists. Radiation has been linked to cardiovascular complications but its effect on cardiac rhythm, specifically, is underexplored. Methods: Demographic, social, occupational, and medical history information was collected from board-certified cardiologists via an electronic survey. Bivariate and multivariable logistic regression analyses were performed to assess the risk of atrial arrhythmias (AA). Results: We received 1,478 responses (8.8% response rate) from cardiologists, of whom 85.4% were male, and 66.1% were ≤65 years of age. Approximately 36% were interventional cardiologists and 16% were electrophysiologists. Cardiologists > 50 years of age, with > 10,000 hours (h) of radiation exposure, had a significantly lower prevalence of AA vs. those with ≤10,000 h (11.1% vs. 16.7%, p = 0.019). A multivariable logistic regression was performed and among cardiologists > 50 years of age, exposure to > 10,000 radiation hours was significantly associated with a lower likelihood of AA, after adjusting for age, sex, diabetes mellitus, hypertension, and obstructive sleep apnea (adjusted OR 0.57; 95% CI 0.38-0.85, p = 0.007). The traditional risk factors for AA (age, sex, hypertension, diabetes mellitus, and obstructive sleep apnea) correlated positively with AA in our data set. Cataracts, a well-established complication of radiation exposure, were more prevalent in those exposed to > 10,000 h of radiation vs. those exposed to ≤10,000 h of radiation, validating the dependent (AA) and independent variables (radiation exposure), respectively. Conclusion: AA prevalence may be inversely associated with radiation exposure in Cardiologists based on self-reported data on diagnosis and radiation hours. Large-scale prospective studies are needed to validate these findings.

Comparison of weight loss data collected by research technicians versus electronic medical records: the PROPEL trial.

BACKGROUND/OBJECTIVES: Pragmatic trials are increasingly used to study the implementation of weight loss interventions in real-world settings. This study compared researcher-measured body weights versus electronic medical record (EMR)-derived body weights from a pragmatic trial conducted in an underserved patient population. SUBJECTS/METHODS: The PROPEL trial randomly allocated 18 clinics to usual care (UC) or to an intensive lifestyle intervention (ILI) designed to promote weight loss. Weight was measured by trained technicians at baseline and at 6, 12, 18, and 24 months. A total of 11 clinics (6 UC/5 ILI) with 577 enrolled patients also provided EMR data (n = 561), which included available body weights over the period of the trial. RESULTS: The total number of assessments were 2638 and 2048 for the researcher-measured and EMR-derived body weight values, respectively. The correlation between researcher-measured and EMR-derived body weights was 0.988 (n = 1 939; p < 0.0001). The mean difference between the EMR and researcher weights (EMR-researcher) was 0.63 (2.65 SD) kg, and a Bland-Altman graph showed good agreement between the two data collection methods; the upper and lower boundaries of the 95% limits of agreement are -4.65 kg and +5.91 kg, and 71 (3.7%) of the values were outside the limits of agreement. However, at 6 months, percent weight loss in the ILI compared to the UC group was 7.3% using researcher-measured data versus 5.5% using EMR-derived data. At 24 months, the weight loss maintenance was 4.6% using the technician-measured data versus 3.5% using EMR-derived data. CONCLUSION: At the group level, body weight data derived from researcher assessments and an EMR showed good agreement; however, the weight loss difference between ILI and UC was blunted when using EMR data. This suggests that weight loss studies that rely on EMR data may require larger sample sizes to detect significant effects. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov number NCT02561221.

Synergies between centralized and federated approaches to data quality: a report from the national COVID cohort collaborative.

OBJECTIVE: In response to COVID-19, the informatics community united to aggregate as much clinical data as possible to characterize this new disease and reduce its impact through collaborative analytics. The National COVID Cohort Collaborative (N3C) is now the largest publicly available HIPAA limited dataset in US history with over 6.4 million patients and is a testament to a partnership of over 100 organizations. MATERIALS AND METHODS: We developed a pipeline for ingesting, harmonizing, and centralizing data from 56 contributing data partners using 4 federated Common Data Models. N3C data quality (DQ) review involves both automated and manual procedures. In the process, several DQ heuristics were discovered in our centralized context, both within the pipeline and during downstream project-based analysis. Feedback to the sites led to many local and centralized DQ improvements. RESULTS: Beyond well-recognized DQ findings, we discovered 15 heuristics relating to source Common Data Model conformance, demographics, COVID tests, conditions, encounters, measurements, observations, coding completeness, and fitness for use. Of 56 sites, 37 sites (66%) demonstrated issues through these heuristics. These 37 sites demonstrated improvement after receiving feedback. DISCUSSION: We encountered site-to-site differences in DQ which would have been challenging to discover using federated checks alone. We have demonstrated that centralized DQ benchmarking reveals unique opportunities for DQ improvement that will support improved research analytics locally and in aggregate. CONCLUSION: By combining rapid, continual assessment of DQ with a large volume of multisite data, it is possible to support more nuanced scientific questions with the scale and rigor that they require.

Anxiety, depression, and end-of-life care utilization in adults with metastatic cancer.

OBJECTIVE: End-of-life care for patients with cancer is often overly burdensome, and palliative and hospice care are underutilized. The objective of this study was to evaluate whether the mental health diagnoses of anxiety and depression were associated with variation in end-of-life care in metastatic cancer. METHODS: This study used electronic health data from 1,333 adults with metastatic cancer who received care at two academic health centers in Louisiana, USA, and died between 1/1/2011-12/31/2017. The study used descriptive statistics to characterize the sample and logistic regression to examine whether anxiety and depression diagnoses in the six months before death were associated with utilization outcomes (chemotherapy, intensive care unit [ICU] visits, emergency department visits, mechanical ventilation, inpatient hospitalization, palliative care encounters, and hospice utilization), while controlling for key demographic and health covariates. RESULTS: Patients (56.1% male; 65.6% White, 31.1% Black) commonly experienced depression (23.9%) and anxiety (27.2%) disorders within six months of death. Anxiety was associated with an increased likelihood of chemotherapy (odds ratio [OR] = 1.42, p = 0.016), ICU visits (OR = 1.40, p = 0.013), and inpatient hospitalizations (OR = 1.85, p < 0.001) in the 30 days before death. Anxiety (OR = 1.95, p < 0.001) and depression (OR = 1.34, p = 0.038) were associated with a greater likelihood of a palliative encounter. CONCLUSIONS: Patients with metastatic cancer who had an anxiety disorder were more likely to have burdensome end-of-life care, including chemotherapy, ICU visits, and inpatient hospitalizations in the 30 days before death. Depression and anxiety both increased the odds of palliative encounters. These results emphasize the importance of mental health considerations in end-of-life care.

The Association Between Neighborhood Social Vulnerability and COVID-19 Testing, Positivity, and Incidence in Alabama and Louisiana.

Racial/ethnic and socioeconomic disparities in COVID-19 burden have been widely reported. Using data from the state health departments of Alabama and Louisiana aggregated to residential Census tracts, we assessed the relationship between social vulnerability and COVID-19 testing rates, test positivity, and incidence. Data were cumulative for the period of February 27, 2020 to October 7, 2020. We estimated the association of the 2018 Social Vulnerability Index (SVI) overall score and theme scores with COVID-19 tests, test positivity, and cases using multivariable negative binomial regressions. We adjusted for rurality with 2010 Rural-Urban Commuting Area codes. Regional effects were modeled as fixed effects of counties/parishes and state health department regions. The analytical sample included 1160 Alabama and 1105 Louisiana Census tracts. In both states, overall social vulnerability and vulnerability themes were significantly associated with increased COVID-19 case rates (RR 1.57, 95% CI 1.45-1.70 for Alabama; RR 1.36, 95% CI 1.26-1.46 for Louisiana). There was increased COVID-19 testing with higher overall vulnerability in Louisiana (RR 1.26, 95% CI 1.14-1.38), but not in Alabama (RR 0.95, 95% CI 0.89-1.02). Consequently, test positivity in Alabama was significantly associated with social vulnerability (RR 1.66, 95% CI 1.57-1.75), whereas no such relationship was observed in Louisiana (RR 1.05, 95% CI 0.98-1.12). Social vulnerability is a risk factor for COVID-19 infection, particularly among racial/ethnic minorities and those in disadvantaged housing conditions without transportation. Increased testing targeted to vulnerable communities may contribute to reduction in test positivity and overall COVID-19 disparities.

Effect of resveratrol on the repair of kidney and brain injuries and its regulation on klotho gene in d-galactose-induced aging mice.

Resveratrol is a natural polyhydroxy trans-stilbene product with many biological activities. One of the most striking biological activities of it is its anti-aging potential. Resveratrol can exhibit anti-aging activity via a variety of signaling pathways, however, the repair effect of it on kidney and brain injury in aging mice induced by d-galactose and its regulation on klotho gene expression have not been reported. Herein, the anti-aging activity of resveratrol and its effect on the repair of kidney and brain injuries in d-galactose-induced aging mice, as well as its regulation of klotho gene expression in these two tissues were investigated. The results indicated that resveratrol could significantly increase the aged cell viability and improve the pathological status of aging mice via inhibiting the formation of malondialdehyde and enhancing the activities of superoxide dismutase and catalase. The histological analysis suggested that resveratrol could remarkably repair the damages of kidney and brain tissues in aging mice. Moreover, PCR and western blot have shown that resveratrol could obviously increase the anti-aging klotho gene expression in the above tissues. The data in this paper further revealed and enriched the anti-aging mechanism of resveratrol, and the methods established in this study can be used as a tool to evaluate the anti-aging activity of drugs to a certain extent.

Racial Disparities in End-of-Life Care Between Black and White Adults With Metastatic Cancer.

CONTEXT: The comfort of patients with cancer near the end of life (EOL) is often undermined by unnecessary and burdensome treatments. There is a need for more research examining racial disparities in EOL care, especially in regions with a history of racial discrimination. OBJECTIVES: To examine whether black adults received more burdensome EOL care than white adults in a population-based data set of cancer decedents in Louisiana, a state with a history of slavery and long-standing racial disparities. METHODS: This was a retrospective analysis of EOL care from the Research Action for Health Network (REACHnet), a regional Patient-Centered Outcomes Research Institute-funded database. The sample consisted of 875 white and 415 black patients with metastatic cancer who died in Louisiana from 2011 to 2017. We used logistic regression to examine whether race was associated with five indicators of burdensome care in the last 30 days of life: chemotherapy use, inpatient hospitalization, intensive care unit admission, emergency department (ED) admission, and mechanical ventilation. RESULTS: Most patients (85.0%) received at least one indicator of burdensome care: hospitalization (76.5%), intensive care unit admission (44.1%), chemotherapy (29.1%), mechanical ventilation (23.0%), and ED admission (18.3%). Odds ratios (ORs) indicated that black individuals were more likely than white individuals to be hospitalized (OR = 1.66; 95% CI = 1.21-2.28; P = 0.002) or admitted to the ED (OR = 1.57; 95% CI = 1.16-2.13; P = 0.004) during their last month of life. CONCLUSION: Findings have implications for informing health care decision making near the EOL for patients, families, and clinicians, especially in regions with a history of racial discrimination and disparities.

Analysis of Pregnancy and Birth Rates Among Black and White Medicaid-Enrolled Teens.

PURPOSE: In the United States, black teens overall have higher pregnancy and birth rates than whites, and it is commonly believed that minority race and low income account for this disparity. We examined racial differences in pregnancy and birth rates among teens from low-income households using Medicaid-enrollment as a proxy for low income. METHODS: This was a retrospective study of Louisiana Medicaid claims data for female teens aged 15-17 years in 2014 (n = 66,069). Pregnancy and pregnancy outcome codes were identified (n = 2,276) and analyzed for differences by black and white race. We conducted validity analyses with different rate definitions and teens' claims status. RESULTS: The cohort was 36% white and 54% black. More black teens than whites lacked any claims data (15.6% vs. 12.6%; p < .001). Rates calculated as events per 1,000 person-years of Medicaid coverage showed no difference in live birth rates between white and black teens (24.6 vs. 25.8; relative incidence ratio, 1.05; 95% confidence interval, .93-1.18; p = .43); however, pregnancy rates for whites were higher than those for blacks (42.7 vs. 36.1; relative incidence ratio, .85; 95% confidence interval, .77-.93; p < .001). CONCLUSION: In contrast to national trends, which include teens from diverse racial and socioeconomic backgrounds, Louisiana Medicaid-enrolled teens aged 15-17 years had equal birth rates regardless of black or white race, and whites had higher pregnancy rates. Decreased racial disparities in pregnancy and birth rates among these adolescents highlights socioeconomic influences in sexual health behavior and a need to examine the interplay of risk factors contributing to racial disparities seen among adolescents nationally.

Inhibitory effects of four anthraquinones on tyrosinase activity: Insight from spectroscopic analysis and molecular docking.

In this study, the inhibitory effects of four anthraquinones including chrysophanol, emodin, physcione and rhein on tyrosinase were investigated by enzyme inhibition assay. The results indicated that all of anthraquinones could significantly inhibit the activity of tyrosinase in a competitive manner. To gain insight into the inhibitory mechanism of anthraquinones on tyrosinase, spectroscopic analysis combined with molecular docking studies were performed. Fluorescence results showed that anthraquinones interacted with tyrosinase by static quenching in a molecular ratio of 1:1. Circular dichroism and molecular docking suggested that anthraquinones could not chelate directly the copper ions but they could bind to amino acid residues in the active site of tyrosinase via electrostatic forces and hydrophobic interactions, as well as hydrogen bonds, and the binding processes resulted in the conformational changes of tyrosinase and prevented the substrate (L-DOPA) from entering the active site, which led to the decrease of tyrosinase activity. Our study in this paper provides a scientific basis for revealing the inhibition of tyrosinase activity by anthraquinone compounds. As a natural inhibitor of tyrosinase, anthraquinones can be used as a potential agent to reduce enzymatic browning reactions, such as food browning and melanization of skin.

Effectiveness of sodium-glucose co-transporter-2 inhibitors on ischaemic heart disease.

AIM: To compare the cardiovascular risks between users and non-users of sodium-glucose co-transporter-2 (SGLT2) inhibitors based on electronic medical record data from a large integrated healthcare system in South Louisiana. MATERIALS AND METHODS: Demographic, anthropometric, laboratory and medication prescription information for patients with type 2 diabetes who were new users of SGLT2 inhibitors, either as initial treatments or as add-on treatments, were obtained from electronic health records. Mediation analysis was performed to evaluate the association of use of SGLT2 inhibitors and changes of metabolic risk factors with the risk of incident ischaemic heart disease. RESULTS: A total of 5338 new users of SGLT2 inhibitors were matched with 13 821 non-users. During a mean follow-up of 3.26 years, 2302 incident cases of ischaemic heart disease were defined. After adjusting for multiple confounding factors, patients using SGLT2 inhibitors had a lower risk of incident ischaemic heart disease compared to patients not using SGLT2 inhibitors (hazard ratio [HR] 0.63, 95% confidence interval [CI] 0.54-0.73). Patients using SGLT2 inhibitors also had a lower risk of incident ischaemic heart disease within 6 months (HR 0.36, 95% CI 0.25-0.44), 12 months (HR 0.40, 95% CI 0.32-0.49), 24 months (HR 0.53, 95% CI 0.43-0.60) and 36 months (HR 0.65, 95% CI 0.54-0.73), respectively. Reductions in systolic blood pressure partly mediated lowering risk of ischaemic heart disease among patients using SGLT2 inhibitors. CONCLUSIONS: The real-world data in the present study show the contribution of SGLT2 inhibitors to reducing risk of ischaemic heart disease, and their benefits beyond glucose-lowering.

Effect of bevacizumab on the expression of fibrosis-related inflammatory mediators in ARPE-19 cells.

AIM: To investigate the effect of anti-vascular epithelial growth factor (VEGF) agents on the expression of fibrosis-related inflammatory mediators under normoxic and hypoxic conditions, and to further clarify the mechanism underlying fibrosis after anti-VEGF therapy. METHODS: Human retinal pigment epithelial (RPE) cells were incubated under normoxic and hypoxic conditions. For hypoxia treatment, CoCl2 at 200 µmol/L was added to the media. ARPE-19 cells were treated as following: 1) control group: no treatment; 2) bevacizumab group: bevacizumab at 0.25 mg/mL was added to the media; 3) hypoxia group: CoCl2 at 200 µmol/L was added to the media; 4) hypoxia+bevacizumab group: CoCl2 at 200 µmol/L and bevacizumab at 0.25 mg/mL were added to the media. The expression of interleukin (IL)-1ß, IL-6, IL-8 and tumor necrosis factor (TNF)-α were evaluated using real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) at 6, 12, 24 and 48h. RESULTS: Both mRNA and protein levels of IL-1ß, IL-6 and IL-8 were statistically significantly higher in the bevacizumab group than in the control group at each time point, and TNF-α gene and protein expression was only significantly higher only at 24 and 48h (P<0.05). Under hypoxic conditions, bevacizumab significantly increased the expression of IL-1ß, IL-6, IL-8 and TNF-α at 6, 12, 24 and 48h (P<0.05). IL-1ß, IL-8 and TNF-α peaked at 24h and IL-6 peaked at 12h after the bevacizumab treatment under both normoxic and hypoxic conditions. CONCLUSION: Treatment of ARPE-19 cells with bevacizumab can significantly increase the expression of fibrosis-related inflammatory mediators under both normoxic and hypoxic conditions. Inflammatory factors might be involved in the process of fibrosis after anti-VEGF therapy, and the up-regulation of inflammatory factors induced by anti-VEGF drugs might promote the fibrosis process.

Bevacizumab modulates retinal pigment epithelial-to-mesenchymal transition via regulating Notch signaling.

AIM: To investigate the effect of bevacizumab treatment on Notch signaling and the induction of epithelial-of-mesenchymal transition (EMT) in human retinal pigment epithelial cells (ARPE-19) in vitro. METHODS: In vitro cultivated ARPE-19 cells were treated with 0.25 mg/mL bevacizumab for 12, 24, and 48h. Cell morphology changes were observed under an inverted microscope. The expression of zonula occludens-1 (ZO-1), vimentin and Notch-1 intracellular domain (NICD) was examined by immunofluorescence. The mRNA levels of ZO-1, α-SMA, Notch-1, Notch-2, Notch-4, Dll4, Jagged-1, RBP-Jk and Hes-1 expression were evaluated with quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of α-SMA, NICD, Hes-1 and Dll-4 expression were examined with Western blot. RESULTS: Bevacizumab stimulation increased the expression of α-SMA and vimentin in ARPE-19 cells which changed into spindle-shaped fibroblast-like cells. Meanwhile, the mRNA expression of Hes-1 increased and the protein expression of Hes-1 and NICD also increased, which Notch signaling was activated. The mRNA expression of Notch-1, Jagged-1 and RBP-Jk increased at 48h, and while Dll4 mRNA and protein expression did not change after bevacizumab treatment. CONCLUSION: Jagged-1/Notch-1 signaling may play a critical role in bevacizumab-induced EMT in ARPE-19 cells, which provides a novel insight into the pathogenesis of intravitreal bevacizumab-associated complication.

Pervasive brain monitoring and data sharing based on multi-tier distributed computing and linked data technology.

EEG-based Brain-computer interfaces (BCI) are facing basic challenges in real-world applications. The technical difficulties in developing truly wearable BCI systems that are capable of making reliable real-time prediction of users' cognitive states in dynamic real-life situations may seem almost insurmountable at times. Fortunately, recent advances in miniature sensors, wireless communication and distributed computing technologies offered promising ways to bridge these chasms. In this paper, we report an attempt to develop a pervasive on-line EEG-BCI system using state-of-art technologies including multi-tier Fog and Cloud Computing, semantic Linked Data search, and adaptive prediction/classification models. To verify our approach, we implement a pilot system by employing wireless dry-electrode EEG headsets and MEMS motion sensors as the front-end devices, Android mobile phones as the personal user interfaces, compact personal computers as the near-end Fog Servers and the computer clusters hosted by the Taiwan National Center for High-performance Computing (NCHC) as the far-end Cloud Servers. We succeeded in conducting synchronous multi-modal global data streaming in March and then running a multi-player on-line EEG-BCI game in September, 2013. We are currently working with the ARL Translational Neuroscience Branch to use our system in real-life personal stress monitoring and the UCSD Movement Disorder Center to conduct in-home Parkinson's disease patient monitoring experiments. We shall proceed to develop the necessary BCI ontology and introduce automatic semantic annotation and progressive model refinement capability to our system.

[The study of vibrational spectra of 3-amino-2, 5-dichlorobenzoic acid by density functional theory].

To understand the relationship between the vibrational spectra and the geometry structure of 3-amino-2, 5-dichlorobenzoic acid (3A2, 5DBA) essentially, geometry optimizations and vibrational frequencies calculation of 3A2, 5DBA were performed at Hartree-Fock (HF) and Becke's three-parameter hybrid functional (B3) for the exchange part and the Lee-Yang-Parr (LYP) correlation function (B3LYP) level using 6-311G(d, p) basis set, respectively. The structural information and 45-complete normal vibrational modes of 3A2, 5DBA were obtained. Comparing the computational geometric parameters of 3A2, 5DBA with the values observed in experimental measurement of benzoic acid as well as the computed vibrational frequencies of 3A2, 5DBA with the reported data of pertinent literature, it was revealed that the results coming from B3LYP/6-311G(d, p) are more reasonable than those by HF/6-311G(d, p). Taking into account the difference between the computed 3A2, 5DBA molecule and the experimental measured sample, the calculated vibrational frequencies were reasonably scaled. Under the B3LYP/6-311G(d, p) method, the scale factor was 1.0013 for the vibrational frequencies with wave numbers <800 cm(-1), while the scale factor was 0.9613 for the vibrational frequencies with wave numbers >800 cm(-1). With the help of Gaussian View software package, the theoretically calculated vibrational frequencies were assigned much more accurately. In addition, the vibrational analysis of substitutive groups and main functional groups of 3A2, 5DBA was carried out. Through the comparison of the calculated vibrational frequencies with the frequencies of 3A2, 5DBA observed in FTIR experiment, the authors found that the theoretically calculated vibrational frequencies scaled reasonably were in excellent agreement with the data coming from experimental measurements. Meanwhile, according to the related literature reports, it was shown that our work done in the paper about vibrational assignments and vibrational analysis of 3A2, 5DBA turned out to be reasonable.