Characterizing variations in ambient PM2.5 concentrations at the U.S. Embassy in Dhaka, Bangladesh using observations and the CMAQ modeling system.

We analyze hourly PM2.5 (particles with an aerodynamic diameter of ≤ 2.5 µm) concentrations measured at the U.S. Embassy in Dhaka over the 2016 - 2021 time period and find that concentrations are seasonally dependent with the highest occurring in winter and the lowest in monsoon seasons. Mean winter PM2.5 concentrations reached ~165-175 µg/m3 while monsoon concentrations remained ~30-35 µg/m3. Annual mean PM2.5 concentration reached ~5-6 times greater than the Bangladesh annual PM2.5 standard of 15 µg/m3. The number of days exceeding the daily PM2.5 standard of 65 µg/m3 in a year approached nearly 50%. Daily-mean PM2.5 concentrations remained elevated (>65 µg/m3) for more than 80 consecutive days. Night-time concentrations were greater than daytime concentrations. The comparison of results obtained from the Community Multiscale Air Quality (CMAQ) model simulations over the Northern Hemisphere using 108-km horizontal grids with observed data suggests that the model can reproduce the seasonal variation of observed data but underpredicts observed PM2.5 in winter months with a normalized mean bias of 13-32%. In the model, organic aerosol is the largest component of PM2.5, of which secondary organic aerosol plays a dominant role. Transboundary pollution has a large impact on the PM2.5 concentration in Dhaka, with an annual mean contribution of ~40 µg/m3.

Pacemaker lead in lung, a rare case.

Pacemaker lead perforation is a rare complication of pacemaker device implantation. We report a case where a ventricular lead perforated through right ventricle, pericardium and went into left lung parenchyma without the development of pericardial effusion, cardiac tamponade, pleural effusion, pneumo or hemo thorax. Patient presented with complaints solely related to failure of pacing rather than disastrous or life threating complications. Echocardiography didn't reveal any evidence of perforation and it was detected on fluoroscopy and computed tomography helped in making the diagnosis. Patient was treated with second procedure where second device placed on other side without manipulating previous device or lead.

Anthropogenic enhancements to production of highly oxygenated molecules from autoxidation.

Atmospheric oxidation of natural and anthropogenic volatile organic compounds (VOCs) leads to secondary organic aerosol (SOA), which constitutes a major and often dominant component of atmospheric fine particulate matter (PM2.5). Recent work demonstrates that rapid autoxidation of organic peroxy radicals (RO2) formed during VOC oxidation results in highly oxygenated organic molecules (HOM) that efficiently form SOA. As NOx emissions decrease, the chemical regime of the atmosphere changes to one in which RO2 autoxidation becomes increasingly important, potentially increasing PM2.5, while oxidant availability driving RO2 formation rates simultaneously declines, possibly slowing regional PM2.5 formation. Using a suite of in situ aircraft observations and laboratory studies of HOM, together with a detailed molecular mechanism, we show that although autoxidation in an archetypal biogenic VOC system becomes more competitive as NOx decreases, absolute HOM production rates decrease due to oxidant reductions, leading to an overall positive coupling between anthropogenic NOx and localized biogenic SOA from autoxidation. This effect is observed in the Atlanta, Georgia, urban plume where HOM is enhanced in the presence of elevated NO, and predictions for Guangzhou, China, where increasing HOM-RO2 production coincides with increases in NO from 1990 to 2010. These results suggest added benefits to PM2.5 abatement strategies come with NOx emission reductions and have implications for aerosol-climate interactions due to changes in global SOA resulting from NOx interactions since the preindustrial era.

Estimating US Background Ozone Using Data Fusion.

US background (US-B) ozone (O3) is the O3 that would be present in the absence of US anthropogenic (US-A) emissions. US-B O3 varies by location and season and can make up a large, sometimes dominant, portion of total O3. Typically, US-B O3 is quantified using a chemical transport model (CTM) though results are uncertain due to potential errors in model process descriptions and inputs, and there are significant differences in various model estimates of US-B O3. We develop and apply a method to fuse observed O3 with US-B O3 simulated by a regional CTM (CMAQ). We apportion the model bias as a function of space and time to US-B and US-A O3. Trends in O3 bias are explored across different simulation years and varying model scales. We found that the CTM US-B O3 estimate was typically biased low in spring and high in fall across years (2016-2017) and model scales. US-A O3 was biased high on average, with bias increasing for coarser resolution simulations. With the application of our data fusion bias adjustment method, we estimate a 28% improvement in the agreement of adjusted US-B O3. Across the four estimates, we found annual mean CTM-simulated US-B O3 ranging from 30 to 37 ppb with the spring mean ranging from 32 to 39 ppb. After applying the bias adjustment, we found annual mean US-B O3 ranging from 32 to 33 ppb with the spring mean ranging from 37 to 39 ppb.

Venom-Induced Consumption Coagulopathy Unresponsive to Antivenom After Echis carinatus sochureki Envenoming.

Snakebite envenoming is a serious and life-threatening but neglected problem in the tropics. The focus in the Indian subcontinent is usually on the Indian cobra (Naja naja), common krait (Bungarus caeruleus), Russell's viper (Daboia russelii), and Indian saw-scaled viper (Echis carinatus). The Indian polyvalent antivenom contains hyperimmunized horse antibodies against only these 4 species. However, regional intraspecific variations are important in viper envenomings, leading to marked differences in clinical presentation and response to the available polyvalent antivenom. Echis carinatus sochureki, a subspecies of Echis carinatus, has been linked to serious morbidity in the Thar Desert regions of Rajasthan, although consistent reports are lacking. We report a patient with prolonged venom-induced consumption coagulopathy owing to Echis carinatus sochureki envenoming who did not respond to Indian polyvalent antivenom in Jodhpur, India. Features of local and hemotoxic envenoming resolved after a week with supportive care. Echis sochureki venom has been shown to be different from Echis carinatus in terms of composition and in vitro neutralization by antivenom. Clinicians in the tropical desert regions must suspect Echis sochureki envenoming in the setting of nonresponsiveness to Indian polyvalent antivenom. This will help optimize antivenom use in these patients, preventing potentially life-threatening antivenom associated reactions. Because the usefulness of Indian polyvalent antivenom appears to be limited in this setting, there is an urgent need to advocate for region-specific antivenom or monovalent antivenom for this area.

Impact of dimethylsulfide chemistry on air quality over the Northern Hemisphere.

We implement oceanic dimethylsulfide (DMS) emissions and its atmospheric chemical reactions into the Community Multiscale Air Quality (CMAQv53) model and perform annual simulations without and with DMS chemistry to quantify its impact on tropospheric composition and air quality over the Northern Hemisphere. DMS chemistry enhances both sulfur dioxide (SO2) and sulfate ( S O 4 2 - ) over seawater and coastal areas. It enhances annual mean surface SO2 concentration by +46 pptv and S O 4 2 - by +0.33 µg/m3 and decreases aerosol nitrate concentration by -0.07 µg/m3 over seawater compared to the simulation without DMS chemistry. The changes decrease with altitude and are limited to the lower atmosphere. Impacts of DMS chemistry on S O 4 2 - are largest in the summer and lowest in the fall due to the seasonality of DMS emissions, atmospheric photochemistry and resultant oxidant levels. Hydroxyl and nitrate radical-initiated pathways oxidize 75% of the DMS while halogen-initiated pathways oxidize 25%. DMS chemistry leads to more acidic particles over seawater by decreasing aerosol pH. Increased S O 4 2 - from DMS enhances atmospheric extinction while lower aerosol nitrate reduces the extinction so that the net effect of DMS chemistry on visibility tends to remain unchanged over most of the seawater.

Management of cardiovascular emergencies during the COVID-19 pandemic.

BACKGROUND: It has been reported that patients attending the emergency department with other pathologies may not have received optimal medical care due to the lockdown measures in the early phase of the COVID-19 pandemic. METHODS: This was a retrospective study of patients presenting with cardiovascular emergencies to four tertiary regional emergency departments in western India during the government implementation of complete lockdown. RESULTS: 25.0% of patients during the lockdown period and 17.4% of patients during the pre-lockdown period presented outside the window period (presentation after 12 hours of symptom onset) compared with only 6% during the pre-COVID period. In the pre-COVID period, 46.9% of patients with ST elevation myocardial infarction underwent emergent catheterisation, while in the pre-lockdown and lockdown periods, these values were 26.1% and 18.8%, respectively. The proportion of patients treated with intravenous thrombolytic therapy increased from 18.4% in the pre-COVID period to 32.3% in the post-lockdown period. Inhospital mortality for acute coronary syndrome (ACS) increased from 2.69% in the pre-COVID period to 7.27% in the post-lockdown period. There was also a significant decline in emergency admissions for non-ACS conditions, such as acute decompensated heart failure and high degree or complete atrioventricular block. CONCLUSION: The COVID-19 pandemic has led to delays in patients seeking care for cardiac problems and also affected the use of optimum therapy in our institutions.

Echocardiographic Pattern of Congenital Heart Diseases in Adolescent and Adult population of Western Rajasthan.

BACKGROUND: Nearly one third of all major congenital anomalies are due to congenital heart disease (CHD). Globally the prevalence of CHD in adults varies from 0.66 to 40.0 per 1000 study population. In India the prevalence of CHD is 1.09 to 543 per 1000 study population. CHD is a major global health burden because of increased mortality and morbidity associated with it. Early diagnosis and management can be helpful in improving survival rates, quality of life and prognosis in patients suffering from CHD. AIMS AND OBJECTIVES: The aim of this study was to assess the echocardiographic profile of CHD in Western Rajasthan, India in population above 12 years of age. METHODS: This retrospective study was carried out at department of Cardiology and Pediatrics of Dr. S. N. Medical College and attached group of hospitals in Jodhpur, Rajasthan, India. The presence of CHD among all patients above 12 years of age who underwent transthoracic echocardiography over a period of around 4 years from July 2014 to April 2018 was analyzed. RESULTS: A total of 256 patients above 12 years of age were identified as having CHD out of the 33,228 patients who underwent echocardiography during the study period, thus giving a prevalence of 7.7 per 1000 study population. Amongst the total diagnosed CHD cases, 137 (53.52%) patients were male with male to female ratio of 1.15:1. CHDs were diagnosed more commonly between 13 to 24 years of age (54.69%). The commonest type of CHD in the present study was atrial septal defect (27.34%) whereas the most common cyanotic CHD was tetralogy of Fallot (10.94%). CONCLUSION: Prevalence of CHD in study cohort of age more than 12 years in Western Rajasthan, India was 7.7 per 1000 study population. Profile of CHDs in the present study was similar to that in published literature. We propose to do larger and targeted studies in this age group because many CHDs will become inoperable or even if operated will leave some or other cardiac dysfunction beyond adolescence.

A New Method for Assessing the Efficacy of Emission Control Strategies.

Regional-scale air quality models and observations at routine air quality monitoring sites are used to determine attainment/non-attainment of the ozone air quality standard in the United States. In current regulatory applications, a regional-scale air quality model is applied for a base year and a future year with reduced emissions using the same meteorological conditions as those in the base year. Because of the stochastic nature of the atmosphere, the same meteorological conditions would not prevail in the future year. Therefore, we use multi-decadal observations to develop a new method for estimating the confidence bounds for the future ozone design value (based on the 4th highest value in the daily maximum 8-hr ozone concentration time series, DM8HR) for each emission loading scenario along with the probability of the design value exceeding a given ozone threshold concentration at all monitoring sites in the contiguous United States. To this end, we spectrally decompose the observed DM8HR ozone time series covering the period from 1981 to 2014 using the Kolmogorov-Zurbenko (KZ) filter and examine the variability in the relative strengths of the short-term variations (induced by synoptic-scale weather fluctuations; referred to as synoptic component, SY) and the long-term component (dictated by changes in emissions, seasonality and other slow-changing processes such as climate change; referred to as baseline component, BL). Results indicate that combining the projected change in the ozone baseline level with the adjusted synoptic forcing in historical ozone observations enables us to provide a probabilistic assessment of the efficacy of a selected emissions control strategy in complying with the ozone standard in future years. In addition, attainment demonstration is illustrated with a real-world application of the proposed methodology by using air quality model simulations, thereby helping build confidence in the use of regional-scale air quality models for supporting regulatory policies.

Influence of bromine and iodine chemistry on annual, seasonal, diurnal, and background ozone: CMAQ simulations over the Northern Hemisphere.

Bromine and iodine chemistry has been updated in the Community Multiscale Air Quality (CMAQ) model to better capture the influence of natural emissions from the oceans on ozone concentrations. Annual simulations were performed using the hemispheric CMAQ model without and with bromine and iodine chemistry. Model results over the Northern Hemisphere show that including bromine and iodine chemistry in CMAQ not only reduces ozone concentrations within the marine boundary layer but also aloft and inland. Bromine and iodine chemistry reduces annual mean surface ozone over seawater by 25%, with lesser ozone reductions over land. The bromine and iodine chemistry decreases ozone concentration without changing the diurnal profile and is active throughout the year. However, it does not have a strong seasonal influence on ozone over the Northern Hemisphere. Model performance of CMAQ is improved by the bromine and iodine chemistry when compared to observations, especially at coastal sites and over seawater. Relative to bromine, iodine chemistry is approximately four times more effective in reducing ozone over seawater over the Northern Hemisphere (on an annual basis). Model results suggest that the chemistry modulates intercontinental transport and lowers the background ozone imported to the United States.

A Call for an Aloft Air Quality Monitoring Network: Need, Feasibility, and Potential Value.

Changing precursor emission patterns in conjunction with stringent health protective air quality standards necessitate accurate quantification of nonlocal contributions to ozone pollution at a location due to atmospheric transport, that by nature predominantly occurs aloft nocturnally. Concerted efforts to characterize ozone aloft on a continuous basis to quantify its contribution to ground-level concentrations, however, are lacking. By applying our classical understanding of air pollution dynamics to analyze variations in widespread surface-level ozone measurements, in conjunction with process-based interpretation from a comprehensive air pollution modeling system and detailed backward-sensitivity calculations that quantitatively link surface-level and aloft pollution, we show that accurate quantification of the amount of ozone in the air entrained from aloft every morning as the atmospheric boundary layer grows is the key missing component for characterizing background pollution at a location, and we propose a cost-effective continuous aloft ozone measurement strategy to address critical scientific gaps in current air quality management. Continuous aloft air pollution measurements can be achieved cost-effectively through leveraging advances in sensor technology and proliferation of tall telecommunications masts. Resultant improvements in ozone distribution characterization at 400-500 m altitude are estimated to be 3-4 times more effective in characterizing the surface-level daily maximum 8-h average ozone (DM8O3) than improvements from surface measurements since they directly quantify the amount of pollution imported to a location and furnish key missing information on processes and sources regulating background ozone and its modulation of ground-level concentrations. Since >80% of the DM8O3 sensitivity to tropospheric ozone is potentially captured through measurements between 200 and 1200 m altitude (a possible design goal for future remote sensing instrumentation), their assimilation will dramatically improve air quality forecast and health advisories.

Percutaneous Transcatheter Treatment of Lutembacher Syndrome.

Lutembacher syndrome is a rare cardiac abnormality characterized by a combination of congenital atrial septal defect (ASD) and acquired rheumatic mitral stenosis (MS). Here we report a case of 18-year-old male with Lutembacher syndrome successfully treated percutaneously with transcatheter Accura balloon valvuloplasty and Amplatzer septal occluder device closure.

Inhibition of demethylase KDM6B sensitizes diffuse large B-cell lymphoma to chemotherapeutic drugs.

Histone methylation and demethylation regulate B-cell development, and their deregulation correlates with tumor chemoresistance in diffuse large B-cell lymphoma, limiting cure rates. Since histone methylation status correlates with disease aggressiveness and relapse, we investigated the therapeutic potential of inhibiting histone 3 Lys27 demethylase KDM6B, in vitro, using the small molecule inhibitor GSK-J4. KDM6B is overexpressed in the germinal center B-cell subtype of diffuse large B-cell lymphoma, and higher KDM6B levels are associated with worse survival in patients with diffuse large B-cell lymphoma treated with R-CHOP. GSK-J4-induced apoptosis was observed in five (SU-DHL-6, OCI-Ly1, Toledo, OCI-Ly8, SU-DHL-8) out of nine germinal center B-cell diffuse large B-cell lymphoma cell lines. Treatment with GSK-J4 predominantly resulted in downregulation of B-cell receptor signaling and BCL6. Cell lines expressing high BCL6 levels or CREBBP/EP300 mutations were sensitive to GSK-J4. Our results suggest that B-cell receptor-dependent downregulation of BCL6 is responsible for GSK-J4-induced cytotoxicity. Furthermore, GSK-J4-mediated inhibition of KDM6B sensitizes germinal center B-cell diffuse large B-cell lymphoma cells to chemotherapy agents that are currently utilized in treatment regimens for diffuse large B-cell lymphoma.

The Impact of Iodide-Mediated Ozone Deposition and Halogen Chemistry on Surface Ozone Concentrations Across the Continental United States.

The air quality of many large coastal areas in the United States is affected by the confluence of polluted urban and relatively clean marine airmasses, each with distinct atmospheric chemistry. In this context, the role of iodide-mediated ozone (O3) deposition over seawater and marine halogen chemistry accounted for in both the lateral boundary conditions and coastal waters surrounding the continental U.S. is examined using the Community Multiscale Air Quality (CMAQ) model. Several nested simulations are conducted in which these halogen processes are implemented separately in the continental U.S. and hemispheric CMAQ domains, the latter providing lateral boundary conditions for the former. Overall, it is the combination of these processes within both the continental U.S. domain and from lateral boundary conditions that lead to the largest reductions in modeled surface O3 concentrations. Predicted reductions in surface O3 concentrations occur mainly along the coast where CMAQ typically has large overpredictions. These results suggest that a realistic representation of halogen processes in marine regions can improve model prediction of O3 concentrations near the coast.

Dynamic Evaluation of Two Decades of WRF-CMAQ Ozone Simulations over the Contiguous United States.

Dynamic evaluation of the fully coupled Weather Research and Forecasting (WRF)- Community Multi-scale Air Quality (CMAQ) model ozone simulations over the contiguous United States (CONUS) using two decades of simulations covering the period from 1990 to 2010 is conducted to assess how well the changes in observed ozone air quality are simulated by the model. The changes induced by variations in meteorology and/or emissions are also evaluated during the same timeframe using spectral decomposition of observed and modeled ozone time series with the aim of identifying the underlying forcing mechanisms that control ozone exceedances and making informed recommendations for the optimal use of regional-scale air quality models. The evaluation is focused on the warm season's (i.e., May-September) daily maximum 8-hr (DM8HR) ozone concentrations, the 4th highest (4th) and average of top 10 DM8HR ozone values (top10), as well as the spectrally-decomposed components of the DM8HR ozone time series using the Kolmogorov-Zurbenko (KZ) filter. Results of the dynamic evaluation are presented for six regions in the U.S., consistent with the National Oceanic and Atmospheric Administration (NOAA) climatic regions. During the earlier 11-yr period (1990-2000), the simulated and observed trends are not statistically significant. During the more recent 2000-2010 period, all trends are statistically significant and WRF-CMAQ captures the observed trend in most regions. Given large number of sites for the 2000-2010 period, the model captures the observed trends in the Southwest (SW) and MW but has significantly different trend from that seen in observations for the other regions. Observational analysis reveals that it is the long-term forcing that dictates how high the ozone exceedances will be; there is a strong linear relationship between the long-term forcing and the 4th highest or the average of the top10 ozone concentrations in both observations and model output. This finding indicates that improving the model's ability to reproduce the long-term component will also enable better simulation of ozone extreme values that are of interest to regulatory agencies.

High reduction of ozone and particulate matter during the 2016 G-20 summit in Hangzhou by forced emission controls of industry and traffic.

Many regions in China experience air pollution episodes because of the rapid urbanization and industrialization over the past decades. Here we analyzed the effect of emission controls implemented during the G-20 2016 Hangzhou summit on air quality. Emission controls included a forced closure of highly polluting industries, and limiting traffic and construction emissions in the cities and surroundings. Particles with aerodynamic diameter lower than 2.5 µm (PM2.5) and ozone (O3) were measured. We also simulated air quality using a forecast system consisting of the two-way coupled Weather Research and Forecast and Community Multi-scale Air Quality (WRF-CMAQ) model. Results show PM2.5 and ozone levels in Hangzhou during the G-20 Summit were considerably lower than previous to the G-20 Summit. The predicted concentrations of ozone were reduced by 25.4%, whereas the predicted concentrations of PM2.5 were reduced by 56%.

14-3-3γ-Mediated transport of plakoglobin to the cell border is required for the initiation of desmosome assembly in vitro and in vivo.

The regulation of cell-cell adhesion is important for the processes of tissue formation and morphogenesis. Here, we report that loss of 14-3-3γ leads to a decrease in cell-cell adhesion and a defect in the transport of plakoglobin and other desmosomal proteins to the cell border in HCT116 cells and cells of the mouse testis. 14-3-3γ binds to plakoglobin in a PKCµ-dependent fashion, resulting in microtubule-dependent transport of plakoglobin to cell borders. Transport of plakoglobin to the border is dependent on the KIF5B-KLC1 complex. Knockdown of KIF5B in HCT116 cells, or in the mouse testis, results in a phenotype similar to that observed upon 14-3-3γ knockdown. Our results suggest that loss of 14-3-3γ leads to decreased desmosome formation and a decrease in cell-cell adhesion in vitro, and in the mouse testis in vivo, leading to defects in testis organization and spermatogenesis.

LncRNA MALAT1 promotes development of mantle cell lymphoma by associating with EZH2.

BACKGROUND: Mantle cell lymphoma (MCL) is considered an aggressive subtype of non-Hodgkin's lymphoma with variable treatment responses. There is an urgent need to identify novel markers with prognostic and therapeutic value for MCL. Long non-coding RNAs (lncRNAs) have emerged as key regulators in cancers, including MCL. Metastasis-associated lung adenocarcinoma transcript 1(MALAT1), a lncRNA located at pathognomonic translocation site of t (11; 14) of MCL. MALAT1 is known to be overexpressed in solid tumors and hematologic malignancies. However, the pathological role and clinical relevance of MALAT1 in MCL are not completely understood. METHODS: We quantified MALAT1 in MCL samples (40) and CD19+ B cells by quantitative real time polymerase chain reaction (qRT-PCR) and correlated levels with clinical outcome. We silenced MALAT1 in MCL cell lines and analyzed cells in tumorigenic assays and formation of transcription complexes. RESULTS: We found that the expression of MALAT1 was elevated in human MCL tumors and cell lines as compared to normal controls, and the elevated levels of MALAT1 correlated with higher MCL international prognostic index (MIPI) and reduced overall survival. MCL with knockdown of MALAT1 showed impaired cell proliferation, facilitated apoptosis and produced fewer clonogenic foci. The increased expression of p21 and p27 upon MALAT1 knockdown was regulated by enhancer of zeste homolog 2 (EZH2). Moreover, decreased phosphorylation of EZH2 at T350 attenuated the binding to MALAT1. CONCLUSIONS: Our findings illuminate the oncogenic role of MALAT1, which may serve as a novel biomarker and as a therapeutic target in MCL.

Unexpected Benefits of Reducing Aerosol Cooling Effects.

Impacts of aerosol cooling are not limited to changes in surface temperature since modulation of atmospheric dynamics resulting from the increased stability can deteriorate local air quality and impact human health. Health impacts from two manifestations of the aerosol direct effects (ADE) are estimated in this study: (1) the effect on surface temperature and (2) the effect on air quality through atmospheric dynamics. Average mortalities arising from the enhancement of surface PM2.5 concentration due to ADE in East Asia, North America and Europe are estimated to be 3-6 times higher than reduced mortality from decreases of temperature due to ADE. Our results suggest that mitigating aerosol pollution is beneficial in decreasing the impacts of climate change arising from these two manifestations of ADE health impacts. Thus, decreasing aerosol pollution gets direct benefits on health, and indirect benefits on health through changes in local climate and not offsetting changes associated only with temperature modulations as traditionally thought. The modulation of air pollution due to ADE also translates into an additional human health dividend in regions (e.g., U.S. Europe) with air pollution control measures but a penalty for regions (e.g., Asia) witnessing rapid deterioration in air quality.

miRNA response to DNA damage.

Faithful transmission of genetic material in eukaryotic cells requires not only accurate DNA replication and chromosome distribution but also the ability to sense and repair spontaneous and induced DNA damage. To maintain genomic integrity, cells undergo a DNA damage response using a complex network of signaling pathways composed of coordinate sensors, transducers and effectors in cell cycle arrest, apoptosis and DNA repair. Emerging evidence has suggested that miRNAs play a crucial role in regulation of DNA damage response. In this review, we discuss the recent findings on how miRNAs interact with the canonical DNA damage response and how miRNA expression is regulated after DNA damage.