Average RBC Research Articles

Association between ferritin, hemoglobin, and anemia response in jaktinib-treated patients with myelofibrosis: A post-hoc analysis of the ZGJAK006 study.

e18527 Background: Iron metabolism is disrupted in MF through the increased production of hepcidin, contributing to increased ferritin levels and iron-binding capacity, decreased serum iron levels and hemoglobin levels. Hepcidin production is upregulated by JAK/STAT pathway and BMP6/ACVR1/SMAD pathway. Jaktinib showed inhibition effects on JAK family and ACVR1 in preclinical studies. Anemia benefits with jaktinib treatment were observed in several clinical studies in MF pts. To explore the underlying mechanisms, we conducted a post-hoc analysis to investigate the change of ferritin levels during jaktinib treatment in MF pts with and without anemia response from a phase 2 study in pts who were intolerant to ruxolitinib (the ZGJAK006 study). Methods: Pts from the ZGJAK006 study were included if they were RBC transfusion dependent or with hemoglobin level ≤100 g/L at baseline. Transfusion dependence was assigned to pts with an average RBC transfusion of ≥2 U/month within 3 months prior to study drug administration. Pts without baseline ferritin results were excluded. Eligible pts were divided into 2 groups: anemia responders by week 24 and non-responders by week 24. Anemia response was defined as becoming RBC transfusion independent (defined by no transfusion in ≥12 consecutive weeks and hemoglobin ≥85 g/L) for transfusion-dependent pts or a ≥20 g/L increase in hemoglobin for non-transfusion-dependent pts with baseline hemoglobin ≤100 g/L. Results: A total of 39 pts were included in this post-hoc analysis, with 14 anemia responders and 25 non-responders. The baseline hemoglobin was similar in responders (median: 78.5 g/L) and non-responders (median: 78.0 g/L). The baseline levels of ferritin were higher than upper limit of normal in most pts (69.2%) with a median of 784.6 ng/mL in the overall population (697.5 ng/mL in responders and 785.0 ng/mL in non-responders). Ferritin decreased to 583.9 and 531.7 ng/mL at weeks 12 and 24, respectively. Notably, anemia responders had a fast reduction in ferritin and increase in hemoglobin compared to non-responders. In addition, the hemoglobin levels of those non-responders maintained were stable and eight non-responders had a ≥50% decrease in RBC infusion frequency or unit. Six (42.9%) of 14 responders and 10 (40.0%) of 25 non-responders achieved spleen volume reduction of ≥ 35% from baseline at week 24. Conclusions: In this post-hoc analysis of pts with anemic MF, jaktinib treatment led to improvement in iron metabolism and anemia. The results were in consistence with the known activities of jaktinib against JAK family and ACVR1. Moreover, similar spleen responses were observed for anemia responders and non-responders. Nevertheless, ferritin was the only marker of iron metabolism measured in this study, a translational biology study evaluating hepcidin may be needed to further support the clinical findings. Clinical trial information: NCT04217993 .

Chemical properties and single-particle mixing state of soot aerosol in Houston during the TRACER campaign

Abstract. A high-resolution soot particle aerosol mass spectrometer (SP-AMS) was used to selectively measure refractory black carbon (rBC) and its associated coating material using both the ensemble size-resolved mass spectral mode and the event trigger single particle (ETSP) mode in Houston, Texas, in summer 2022. This study was conducted as part of the Department of Energy Atmospheric Radiation Measurement (ARM) program's TRacking Aerosol Convection interactions ExpeRiment (TRACER) field campaign. The study revealed an average (±1σ) rBC concentration of 103 ± 176 ng m−3. Additionally, the coatings on the BC particles were primarily composed of organics (59 %; 219 ± 260 ng m−3) and sulfate (26 %; 94 ± 55 ng m−3). Positive matrix factorization (PMF) analysis of the ensemble mass spectra of BC-containing particles resolved four distinct types of soot aerosol, including an oxidized organic aerosol (OOABC,PMF) factor associated with processed primary organic aerosol, an inorganic sulfate factor (SO4,BC,PMF), an oxidized rBC factor (O-BCPMF), and a mixed mineral dust–biomass burning aerosol factor with significant contribution from potassium (K-BBBC,PMF). Additionally, K-means clustering analysis of the single-particle mass spectra identified eight different clusters, including soot particles enriched in hydrocarbon-like organic aerosol (HOABC,ETSP), sulfate (SO4,BC,ETSP), two types of rBC, OOA (OOABC,ETSP), chloride (ClBC,ETSP), and nitrate (NO3,BC,ETSP). The single-particle measurements demonstrate substantial variation in BC coating thickness with coating-to-rBC mass ratios ranging from 0.1 to 100. The mixing state index (χ), which denotes the degree of homogeneity of the soot aerosol, varied from 4 % to 94 % with a median of 40 %, indicating that the aerosol population lies in between internal and external mixing but has large temporal and source type variability. In addition, a significant fraction of BC-containing particles, a majority enriched with oxidized organics and sulfate, exhibit sufficiently high κ values and diameters conducive to activation as cloud nuclei under atmospherically relevant supersaturation conditions. This finding bears significance in comprehending the aging processes of rBC-containing particles and their activation into cloud droplets. Our analysis highlights the complex nature of soot aerosol and underscores the need to comprehend its variability across different environments for accurate assessment of climate change.

Dysregulation of LncRNAs ANRIL, MALAT1, and LINC00305 in Coronary Slow Flow Patients: Implications for Inflammation and Endothelial Dysfunction.

Coronary Slow Flow (CSF) is observed in individuals who experience delayed blood supply in the coronary arteries. Inflammation and endothelial dysfunction may play a role in the etiology and development of CSF. The current investigation aimed to compare the expression of specific long noncoding RNAs (lncRNAs) associated with endothelial dysfunction and inflammation in CSF patients. This case‒control study enrolled 72 CSF patients and 71 healthy individuals. Blood samples were collected, and serum marker levels were measured. The expression levels of lncRNAs ANRIL, MALAT1, and LINC00305 in peripheral blood mononuclear cells (PBMCs) were assessed using real-time Polymerase Chain Reaction (PCR). All statistical analyses were performed using SPSS 22, with the significance level set at P < 0.05. The study revealed that the relative expression of MALAT1 and LINC00305 was significantly lower in the CSF group (p < 0.01), whereas ANRIL was expressed at higher levels (p < 0.0001). The areas under the ROC curves (AUCs) for MALAT1, LINC00305, and ANRIL were 0.64, 0.66, and 0.75, respectively. Notably, the expression level of LINC00305 exhibited an inverse correlation with CSF incidence (OR: 0.83, p: 0.008) in contrast to that of ANRIL (OR: 1.43, p < 0.0001). Additionally, compared to those in the control group, the average BMI, WBC, RBC, Hb, LDH, LDL, FBS, and percentage of neutrophils in the CSF group were significantly greater (p< 0.05). lncRNA ANRIL is upregulated in CSF patients, whereas MALAT1 and LINC00305 are downregulated. Dysregulation of ANRIL, MALAT1, and LINC00305 may serve as diagnostic and predictive factors for CSF leakage.

Effect of resveratrol on haematological changes in diabetic-malaria infected wistar rats

The effect of resveratrol on haematological changes in diabetic-malaria infected rats was investigated. Five of six groups of male Wistar rats were induced with type 2 diabetes, followed by inoculation with malaria parasites. Four groups of the diabetic-malaria infected rats were orally given: low dose resveratrol (50 mg/kg), high dose resveratrol (100 mg/kg), Metformin (100 mg/kg) and Artesunate (5 mg/kg) respectively for six days after malaria inoculation. Administration of resveratrol, metformin and artesunate to diabetic-malaria infected rats significantly (p &lt; 0.05) decreased the blood glucose level (BGL) on days 3 and 6 post-inoculation. The high dose resveratrol (RSV 100) group showed a significant (p&lt;0.05) increase in red blood cell counts, although a significant (p &lt; 0.05) decrease of Packed Cell Volume was recorded in the low dose resveratrol group. There was no significant (p&gt;0.05) difference for the values of total WBC counts across the four groups of the diabetic-malaria infected rats, but the differential WBC counts (dWBCC) were significantly (p&lt;0.05) affected. High dose resveratrol administration significantly (p &lt; 0.05) reversed the dWBCC. The diabetic-malarial infected group showed significant (p&lt;0.05) decrease in average RBC; the average parasites and average infected RBC counts were significantly (p&lt;0.05) higher than that in the resveratrol groups. While, Metformin and Artesunate groups showed a further decline in parasitaemia. These findings indicate that Resveratrol decreased BGL and improved hematological parameters and suppressed parasitaemia in diabetic-malarial infected rats.

Radiation-Induced Lung Injury Quantified by Hyperpolarized 129Xe MRI: Dose-Dependence and Association with Changes in Global Lung Function

<h3>Purpose/Objective(s)</h3> To quantify radiation therapy (RT)-induced dose-dependent changes in regional lung function (including pulmonary gas exchange), and their association with changes in global lung function. <h3>Materials/Methods</h3> Ten patients receiving conventional thoracic RT for lung cancer underwent pre-RT and 3-month post-RT MRI using an established hyperpolarized ¹²⁹Xe technique to map lung function. Four patients underwent additional ¹²⁹Xe MRI at 6-months post-RT. During ¹²⁹Xe MRI, the xenon signal is measured in three pulmonary compartments: the lung airspaces (indicating ventilation), the alveolar barrier (indicating tissue uptake), and interacting with capillary red blood cells, RBC (indicating gas exchange). During the same MRI session, a thoracic ¹H MRI is acquired for deformable registration of ¹²⁹Xe functional maps to the planning CT. The pre- vs. post-RT changes in ventilation, barrier uptake, and RBC transfer were computed as a function of regional lung dose, excluding ventilation-defects and high dose-gradient areas. Least-squares regression was used to define the dose-dependence of lung voxels receiving between 5-50Gy. Per patient, changes in whole-lung average xenon-measured function (i.e., the sum of regional injuries) were compared to changes in two pulmonary function tests, forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO), by calculating Pearson correlation. <h3>Results</h3> At 3-months post-RT, ventilation decreased by -0.26%/Gy (R²=0.90), barrier uptake increased by 0.76%/Gy (R²=0.92), and RBC transfer decreased by -0.67%/Gy (R²=0.78) compared to the pre-RT baseline examination. The 6-month post-RT data also demonstrated a strong correlation between local RT dose and an increase in barrier uptake, at a rate of 0.76%/Gy (R²=0.87), compared to baseline. A decrease in ventilation (-0.19%/Gy, R²=0.20) and an increase in RBC transfer (0.26%/Gy, R²=0.26) were also observed at 6-months, but correlation with RT dose was poor. Examining per-patient pulmonary function 3-months after RT, moderate correlation was observed between the increase in whole-lung average barrier uptake and decreases in FVC (ρ=0.56, P=0.15) and DLCO (ρ=0.52, P=0.18), and between the increase in average RBC transfer and decrease in FVC (ρ=0.52, P=0.19). No correlation was observed between changes in whole-lung average ventilation and PFTs. <h3>Conclusion</h3> Hyperpolarized ¹²⁹Xe MRI was able to detect and quantify RT-induced dose-dependent changes in regional lung function, including pulmonary gas exchange. Additional work is needed to better define the role of ¹²⁹Xe MRI-based functional lung imaging to understand and predict RT-associated lung injury.

Characteristics and source apportionment of black carbon aerosol in the North China Plain

In this study, the physical properties of refractory BC (rBC) including mass concentration, core size distribution and mixing state were in-situ characterized with a single particle soot photometer (SP2) at a polluted rural site in the North China Plain in November 2018. The average rBC mass concentration is 4.12 ± 2.47 μg m−3, accounting for 6.26% of PM1 mass. Its diurnal variation shows that the rBC concentration is affected by both the local residential activities and the evolution of planetary boundary layer (PBL). And a broader rBC core mass size distribution (CMSD) can be observed in the afternoon. The CMSD show a primary mode with peak diameter (Dm) of ~222 nm, and a small secondary mode with Dm of ~687 nm. The average absolute coating thickness (ACT) of rBC particles is 50 nm and the bulk relative coating thickness (BRCT) is about 1.7, indicating a relatively high aging level of rBC. The correlation analysis between SP2-separated rBC and PMF-separated OA factors indicate that rBC with different core size (Dc) and ACT may be originated from different sources. The rBC contributed by coal combustion is distributed throughout a large Dc range (~70–500 nm). The rBC particles emitted by traffic sources have small core sizes and thin coating thickness (Dc < 180 nm and ACT <50 nm); while the rBC particles emitted from biomass burning show a higher degree of aging (ACT >250 nm). In addition, the secondary mode of rBC particles are likely to be originated from coal combustion.

The Influence of Low-Dose Occupational Radiation Exposure on Peripheral Blood Cell in a Cohort Chinese Medical Radiation Workers

The study aims to assess the change of peripheral blood cell number following protracted low-dose radiation exposure among medical radiation workers.A cohort of 185 Chinese radiation workers which divided into 4 groups by different occupational categories which include Interventional radiologists group (IRG); nuclear medicine doctors group (NMD); medical diagnostic radiographers group (MDR); radiologists group (RG) were followed by 5 years (2015-2019). This study observed and recorded the changes in the cumulative dose and peripheral blood cell counts consecutively for five years. While exploring the changes in blood cells and cumulative dose, the correlation between dose and the quantity of peripheral blood cells was also discussed. Individual doses were recorded by dose monitoring system. The counts of peripheral blood cell were based on the physical examination data of the workers of the annual physical examination in the hospitality-test, SD-T test and Variance analysis were used to analyze the radiation dose-response changes of the peripheral blood cell. Correlation analysis was used to analyze the correlation between the number of peripheral blood cells and the cumulative dose.The results of this study showed that compared with the control group, the number of white blood cells (WBCs), the number of hemoglobin (Hb) and the ratio of eosinophils (EO%) in the study group decreased (P < 0.05). Correlation analysis between the average cumulative dose in different years and the number of peripheral blood cells in different groups showed that the average cumulative dose of nuclear medicine group in 2016 was negatively correlated with WBC (r = -0.602, P < 0.05) and NE% (r = -0.596, P < 0.05). There was a significant positive correlation between the average cumulative dose of the radiological diagnosis group in 2015 and MO% (r = 0.530, P < 0.01). For the radiologists' group, there was a significant negative correlation between the average cumulative dose and the number of WBCs in 2016 (r = -3.37, P < 0.05), and there was a significant negative correlation between the average cumulative dose and RBC in 2017 (r = -4.12, P < 0.05).The results of the study suggest that the blood cell levels of workers exposed to low-dose ionizing radiation for a long time can show dynamic changes, and relevant workers should take appropriate protection measures and regularly monitor peripheral blood cell indicators.

Drought-induced biomass burning as a source of black carbon to the central Himalaya since 1781 CE as reconstructed from the Dasuopu ice core

Abstract. Himalayan glaciers are melting due to atmospheric warming, with the potential to limit access to water for more than 25 % of the global population that resides in these glacier meltwater catchments. Black carbon has been implicated as a factor that is contributing to Himalayan glacier melt, but its sources and mechanisms of delivery to the Himalayas remain controversial. Here, we provide a 211-year ice core record spanning 1781–1992 CE for refractory black carbon (rBC) deposition from the Dasuopu glacier ice core that has to date provided the highest-elevation ice core record (7200 m). We report an average rBC concentration of 1.5 µg L−1 (SD=5.0, n=1628) over the 211-year period. An increase in the frequency and magnitude of rBC deposition occurs after 1877 CE, accompanied by decreased snow accumulation associated with a shift in the North Atlantic Oscillation Index to a positive phase. Typically, rBC is deposited onto Dasuopu glacier during the non-monsoon season, and short-lived increases in rBC concentration are associated with periods of drought within neighboring regions in northwestern India, Afghanistan, and Pakistan. Using a combination of spectral and back-trajectory analyses, as well as a comparison with a concurrent analysis of trace metals at equivalent depths in the same ice core, we show that biomass burning resulting from dry conditions is a source of rBC to the central Himalaya and is responsible for deposition that is up to 60 times higher than the average rBC concentration over the time period analyzed. We suggest that biomass burning is a significant source of rBC to the central Himalaya and that the rBC record can be used to identify periods of drought in nearby regions that are upwind of Dasuopu glacier.

Clinical profile of hypochromic microcytic anemia in Chittoor district, India

Background: Anemia is not a diagnosis by itself like fever but merely is an objective sign of the presence of disease. The correct diagnostic terminology for a child with anemia requires the detection of etiology, pathology, and pathogenesis of the anemia. To evaluate the role of therapeutic oral iron therapy as a diagnostic approach to hypochromic microcytic anemia.Methods: The present study is a retrospective study conducted at the teaching hospital, Chittoor district from September 2019 to December 2019. A total number of 350 cases of anemia were studied from both inpatient and outpatient services in the age group 2 months to 12 years. Hemogram, Hb Electrophoresis, and bone marrow study as necessary based on individual cases.Results: From the above analysis, the mean Hb% at the time of entry to study was 7.36gms%. The mean Hb% after the iron therapy was 11.8gms%. The mean increase in Hb was 4.4gms%. In this study, the average RBC count was 2.9 million cells/cumm.Conclusions: A therapeutic trial of oral iron is an appropriate initial step in the diagnostic approach of hypochromic microcytic anemia. Costly investigations like Hb electrophoresis and bone marrow study are required only in selected cases.

Sources and physicochemical characteristics of black carbon aerosol from the southeastern Tibetan Plateau: internal mixing enhances light absorption

Abstract. Black carbon (BC) aerosol has important effects on the climate and hydrology of the Tibetan Plateau (TP). An intensive measurement campaign was conducted at Lulang (∼ 3300 m a.s.l. – above sea level), southeastern TP, from September to October 2015, to investigate the sources and physicochemical characteristics of refractory BC (rBC) aerosol. The average rBC mass concentration was 0.31 ± 0.55 µg m−3, which is higher than most prior results for BC on the TP. A clear diurnal cycle in rBC showed high values in the morning and low values in the afternoon. A bivariate polar plot showed that rBC loadings varied with wind speed and direction, which also reflected the dominant transport direction. The estimated net surface rBC transport intensity was +0.05 ± 0.29 µg s−1 m−2, indicating stronger transport from outside the TP compared with its interior. Cluster analysis and a concentration-weighted trajectory model connected emissions from north India to the high rBC loadings, but the effects of internal TP sources should not be overlooked. The average mass median diameter (MMD) of rBC was 160 ± 23 nm, with smaller MMDs on rainy days (145 nm) compared with non-rainy days (164 nm). The average number fraction of thickly coated rBC (FrBC) was 39 ± 8 %, and it increased with the O3 mixing ratios from 10:00 to 14:00 LT, indicating that photochemical oxidation played a role in forming rBC coatings. The average rBC absorption enhancement (Eabs) was estimated to be 1.9, suggesting that light absorption by coated rBC particles was greater than for uncoated ones. The Eabs was strongly positively correlated with the FrBC, indicating an amplification of light absorption for internally mixed rBC. For rBC cores &lt; 170 nm, Eabs was negatively correlated with MMD, but it was nearly constant for rBC cores &gt; 170 nm. Our study provides insight into the sources and evolution of rBC aerosol on the TP, and the results should be useful for improving models of the radiative effects of carbonaceous aerosols in this area.

Steady-state relationship between average glucose, HbA1c and RBC lifespan

HbA1c is used to estimate average glucose. Previous studies showed linear relationship between average glucose and HbA1c. We made a new theoretical relationship using recently proposed Γ-like function model of erythrocyte lifespan. We showed the relationship between average glucose and HbA1c; we approximated it into a simple hyperbolic function: HbA1c=MRBCkgAG/(1+(2/3)MRBCkgAG), whose inverse function is easily obtained. Apparent linear relationship is an approximation of the curved relationship. Hyperbolic function would provide a more accurate approximation than a linear equation. Physicians should keep in mind the curved relationship and be aware that extremely high HbA1c indicates acceleratingly high glucose level.

RBC Transfusion Practice in Pediatric Extracorporeal Membrane Oxygenation Support.

To determine RBC transfusion practice and relationships between RBC transfusion volume and mortality in infants and children treated with extracorporeal membrane oxygenation. Secondary analysis of a multicenter prospective observational study. Eight pediatric institutions within the Eunice Kennedy Shriver National Institute of Child Health and Human Development's Collaborative Pediatric Critical Care Research Network. Patients age less than 19 years old treated with extracorporeal membrane oxygenation at a participating center. None. Clinical data and target hemoglobin or hematocrit values (if set) were recorded daily by trained bedside extracorporeal membrane oxygenation specialists and research coordinators. Laboratory values, including hemoglobin and hematocrit, were recorded daily using the value obtained closest to 8:00 AM. RBC transfusion was recorded as total daily volume in mL/kg. Multivariable logistic regression was used to determine the relationship between RBC transfusion volume and hospital mortality, accounting for potential confounders. Average goal hematocrits varied across the cohort with a range of 27.5-41.3%. Overall, actual average daily hematocrit was 36.8%, and average RBC transfusion volume was 29.4 mL/kg/d (17.4-49.7 mL/kg/d) on extracorporeal membrane oxygenation. On multivariable analysis, each additional 10 mL/kg/d of RBC transfusion volume was independently associated with a 9% increase in odds of hospital mortality (adjusted odds ratio, 1.09 [1.02-1.16]; p = 0.009). In this multicenter cohort of pediatric extracorporeal membrane oxygenation patients, daily hematocrit levels were maintained at normal or near-normal values and RBC transfusion burden was high. RBC transfusion volume was independently associated with odds of mortality. Future clinical studies to identify optimum RBC transfusion thresholds for pediatric extracorporeal membrane oxygenation are urgently needed.

Enhanced light absorption due to the mixing state of black carbon in fresh biomass burning emissions

A lack of information on the radiative effects of refractory black carbon (rBC) emitted from biomass burning is a significant gap in our understanding of climate change. A custom-made combustion chamber was used to simulate the open burning of crop residues and investigate the impacts of rBC size and mixing state on the particles' optical properties. Average rBC mass median diameters ranged from 141 to 162 nm for the rBC produced from different types of crop residues. The number fraction of thickly-coated rBC varied from 53 to 64%, suggesting that a majority of the freshly emitted rBC were internally mixed. By comparing the result of observed mass absorption cross-section to that calculated with Mie theory, large light absorption enhancement factors (1.7–1.9) were found for coated particles relative to uncoated cores. These effects were strongly positively correlated with the percentage of coated particles but independent of rBC core size. We suggest that rBC from open biomass burning may have strong impact on air pollution and radiative forcing immediately after their production.

Physicochemical characteristics of black carbon aerosol and its radiative impact in a polluted urban area of China

AbstractBlack carbon (BC) aerosol plays an important role in the Earth's radiative balance. An intensive measurement campaign was conducted at Xi'an, China, from December 2012 to January 2013 to investigate the sources and physicochemical characteristics of refractory BC (rBC) and its direct radiative forcing at the surface. The overall average rBC concentration for the campaign was 8.0 ± 7.1 µg m−3. Source apportionment based on positive matrix factorization showed that traffic was the dominant rBC source (46.0%), followed by coal burning (33.9%) and biomass burning (20.1%). The rBC mass size distributions were monomodal and lognormal with larger mass median diameters for coal burning source (215 nm) compared with the traffic source (189 nm). Coal burning rBC was more strongly associated with sulfate than traffic rBC, suggesting a higher cloud condensation nuclei activity. The slope of a robust linear regression between rBC and carbon monoxide (CO) for all samples was 5.9 µg m−3 ppm−1, and the slope for the coal burning source (4.5 µg m−3 ppm−1) was larger than that for the traffic source (2.7 µg m−3 ppm−1). The net rBC emission during winter of 2009 was estimated to be 4.5 Gg based on the relationship between rBC and CO. A Tropospheric Ultraviolet and Visible radiation model showed that the average daytime value for the clear‐sky direct radiative forcing due to rBC from 23 December 2012 to 31 January 2013 was −47.7 ± 28.9 W m−2, which amounted to an average of 45.7% of the total surface atmospheric aerosol forcing.

Size distribution and mixing state of refractory black carbon aerosol from a coastal city in South China

An intensive measurement campaign was conducted in the coastal city of Xiamen, China to investigate the size distribution and mixing state of the refractory black carbon (rBC) aerosol. The average rBC concentration for the campaign, measured with a ground-based single particle soot photometer (SP2), was 2.3±1.7μgm−3, which accounted for ~4.3% of the PM2.5 mass. A potential source contribution function model indicated that emissions from coastal cities to the southwest were the most important source for the rBC and that shipping traffic was another likely source. The mass size distribution of the rBC particles was mono-modal and approximately lognormal, with a mass median diameter (MMD) of ~185nm. Larger MMDs (~195nm) occurred during polluted conditions compared with non-polluted times (~175nm) due to stronger biomass burning activities during pollution episodes. Uncoated or thinly-coated particles composed the bulk of the rBC aerosol, and on average ~31% of the rBC was internally-mixed or thickly-coated. A positive matrix factorization model showed that organic materials were the predominant component of the rBC coatings and that mixing with nitrate increased during pollution conditions. These findings should lead to improvements in the parameterizations used to model the radiative effects of rBC.

A protocol for management of blood loss in surgical treatment of peritoneal malignancy by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

The treatment of peritoneal malignancies with cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to be associated with massive surgical blood loss. Maintaining high fibrinogen levels throughout surgery may reduce blood loss in these patients. The primary aim of the study was to see if Tranexamic Acid (TXA) and cryoprecipitate reduced surgical blood loss and hence red cell transfusions. A comparison was made with a cohort of patients treated with fresh frozen plasma (FFP) alone. The secondary aim was to measure the effect of both protocols on coagulation parameters and the incidence of arterial or venous thrombosis. We used prospectively collected data from 201 patients who had complete CRS with HIPEC for peritoneal malignancy using different protocols during two discrete 12-month time periods. The new transfusion protocol led to a higher average fibrinogen level intra-operatively and post-operatively, with a significant reduction in average RBC, FFP and platelet transfusion intra-operatively per patient from 4·2 to 1·8 units, 6·2 to 0·2 units and 0·1 to 0 units, respectively. No significant difference in PT or APTT was seen between patients treated with the standard and new protocols. Venous thrombosis occurred in seven patients treated with the standard protocol and five with the new protocol. A single case of arterial thrombosis was seen in both groups. Patients treated with upfront TXA and cryoprecipitate during CRS required less RBC transfusion than those treated with the standard protocol of early FFP.

Induction of Fetal Hemoglobin and Reduction of Disease Pathology in Sickle Cell Mice By a Synthetic Zinc Finger Gamma-Globin Activator

A plethora of research has established that the most effective treatment for sickle cell disease (SCD) is increased fetal hemoglobin (HbF). Fetal hemoglobin normally accounts for less than 0.5% of total hemoglobin in adults; increasing levels to approximately 10% alleviates much of the pathophysiology associated with SCD. Hydroxyurea is the only FDA-approved treatment for SCD that results in enhanced HbF production, but this drug is highly pleiotropic in its action and does not exclusively modulate γ-globin gene expression. Thus, research has focused on identifying agents that specifically reactivate γ-globin gene expression during adult definitive erythropoiesis, with minimal off-target effects. Artificial transcription factors (ATFs) are synthetic proteins designed to bind at a specific DNA sequence and modulate gene expression. The artificial zinc finger gg1-VP64 was designed to target the -117 region of the A γ-globin gene proximal promoter and activate expression of this gene. Previous studies demonstrated that HbF levels were increased in K562 cells, murine chemical inducer of dimerization (CID)-dependent bone marrow cells carrying a human β-globin locus yeast artificial chromosome (β-YAC) transgene, in CD34+ erythroid progenitor cells from normal donors and β-thalassemia patients, and in vivo, in gg1-VP64 β-YAC double transgenic (bigenic) mice. Transgenic mice with enforced expression of the gg1-VP64 fusion protein only in the erythroid-megakaryocytic compartment were crossed into the Townes sickle cell knock-in mouse (Jackson Laboratory) background. Compared with control sickle cell (HbSS) mice, gg1-VP64 ATF sickle cell (gg1-HbSS) mice had hematological values at levels found in wild-type homozygous or heterozygous adult hemoglobin (HbAA or HbAS, respectively) mice. For example, average RBC (106/mm3) was 11.7 for wild-type mice and 12.9 for gg1 HbSS, compared to 8.2 for HbSS mice. Average HGB (g/dl) was 15.1 for wild-type mice and gg1 HbSS mice, versus 10.0 for HbSS mice. Average HCT was 52.5% for wild-type mice, 53.7% for gg1 HbSS mice, but only 41.5% for HbSS mice. Finally, average WBC (103/mm3) was 9.4 for wild-type mice, 9.0 for gg1 HbSS mice and 91.0 for HbSS mice. HPLC and Western blot analysis to determine the effect of gg1-VP64 on HbF synthesis are underway. In addition, we are examining mice for numbers of HbF-positive cells, mature cells, and reticulocytes, as well as looking at organ damage. Our results demonstrate that the ATF class of reagent may be an effective gene therapy for treatment of SCD. DisclosuresMakala:Georgia Regents University: Employment.

Mixing State of Black Carbon Aerosol in a Heavily Polluted Urban Area of China: Implications for Light Absorption Enhancement

Black carbon (BC) is important for climate forcing, and its effects on the Earth’s radiative balance remain a major uncertainty in climate models. In this study, we investigated the mixing state of refractory black carbon (rBC) and aerosol optical properties in a polluted atmosphere at Xi’an, western China. The average rBC mass concentration was 9.9 m gm i3 during polluted periods, 7.6 times higher than that in clean periods. About 48.6% of the rBC was internally-mixed or coated with nonrefractory materials during polluted periods; this was 27% higher than in clean periods. Correlation analysis between the number fraction of thickly-coated rBC particles (fBC) and the major particulate species indicate that organics may be the primary contributor to rBC coatings during polluted periods. The average mass absorption cross section of rBC (MACBC) particles at l D 870 nm was 7.6 § 0.02 m 2 g i1 for the entire campaign. The MACBC showed a positive correlation with fBC, and the enhancement of MACBC due to internal mixing was 1.8 times. These observations suggest that an enhancement of BC absorption by a factor of � 2 could be appropriate for climate models associated with high PM2.5 levels.

Human erythrocytes analyzed by generalized 2D Raman correlation spectroscopy

The most numerous elements of the blood cells, erythrocytes, consist mainly of two components: homogeneous interior filled with hemoglobin and closure which is the cell membrane. To gain insight into their specific properties we studied the process of disintegration, considering these two constituents, and comparing the natural aging process of human healthy blood cells.MicroRaman spectra of hemoglobin within the single RBC were recorded using 514.5, and 785nm laser lines. The generalized 2D correlation method was applied to analyze the collected spectra. The time passed from blood donation was regarded as an external perturbation. The time was no more than 40days according to the current storage limit of blood banks, although, the average RBC life span is 120days. An analysis of the prominent synchronous and asynchronous cross peaks allow us to get insight into the mechanism of hemoglobin decomposition. Appearing asynchronous cross-peaks point towards globin and heme separation from each other, while synchronous shows already broken globin into individual amino acids.Raman scattering analysis of hemoglobin “wrapping”, i.e. healthy erythrocyte ghosts, allows for the following peculiarity of their behavior. The increasing power of the excitation laser induced alterations in the assemblage of membrane lipids. 2D correlation maps, obtained with increasing laser power recognized as an external perturbation, allows for the consideration of alterations in the erythrocyte membrane structure and composition, which occurs first in the proteins. Cross-peaks were observed indicating an asynchronous correlation between the senescent-cell antigen (SCA) and heme or proteins vibrations.The EPR spectra of the whole blood was analyzed regarding time as an external stimulus. The 2D correlation spectra points towards participation of the selected metal ion centers in the disintegration process.

Black carbon aerosol characterization in a remote area of Qinghai–Tibetan Plateau, western China

The concentrations, size distributions, and mixing states of refractory black carbon (rBC) aerosols were measured with a ground-based Single Particle Soot Photometer (SP2), and aerosol absorption was measured with an Aethalometer at Qinghai Lake (QHL), a rural area in the Northeastern Tibetan Plateau of China in October 2011. The area was not pristine, with an average rBC mass concentration of 0.36μgSTP-m−3 during the two-week campaign period. The rBC concentration peaked at night and reached the minimal in the afternoon. This diurnal cycle of concentration is negatively correlated with the mixed layer depth and ventilation. When air masses from the west of QHL were sampled in late afternoon to early evening, the average rBC concentration of 0.21μgSTP-m−3 was observed, representing the rBC level in a larger Tibetan Plateau region because of the highest mixed layer depth. A lognormal primary mode with mass median diameter (MMD) of ~175nm, and a small secondary lognormal mode with MMD of 470–500nm of rBC were observed. Relative reduction in the secondary mode during a snow event supports recent work that suggested size dependent removal of rBC by precipitation. About 50% of the observed rBC cores were identified as thickly coated by non-BC material. A comparison of the Aethalometer and SP2 measurements suggests that non-BC species significantly affect the Aethalometer measurements in this region. A scaling factor for the Aethalometer data at a wavelength of 880nm is therefore calculated based on the measurements, which may be used to correct other Aethalometer datasets collected in this region for a more accurate estimate of the rBC loading. The results present here significantly improve our understanding of the characteristics of rBC aerosol in the less studied Tibetan Plateau region and further highlight the size dependent removal of BC via precipitation.