Radiation Biological Toximetry Using Circulating Cell-Free DNA (cfDNA) for Rapid Radiation/Nuclear Triage.

Optimal triage biodosimetry would include risk stratification within minutes, and it would provide useful triage despite heterogeneous dosimetry, cytokine therapy, mixed radiation quality, race, and age. For regulatory approval, the U.S. Food and Drug Administration (FDA) Biodosimetry Guidance requires suitability for purpose and a validated species-independent mechanism. Circulating cell-free DNA (cfDNA) concentration assays may provide such triage information. To test this hypothesis, cfDNA concentrations were measured in unprocessed monkey plasma using a branched DNA (bDNA) technique with a laboratory developed test. The cfDNA levels, along with hematopoietic parameters, were measured over a 7-day period in Rhesus macaques receiving total body radiation doses ranging from 1 to 6.5 Gy. Low-dose irradiation (0-2 Gy) was easily distinguished from high-dose whole-body exposures (5.5 and 6.5 Gy). Fold changes in cfDNA in the monkey model were comparable to those measured in a bone marrow transplant patient receiving a supralethal radiation dose, suggesting that the lethal threshold of cfDNA concentrations may be similar across species. Average cfDNA levels were 50 ± 40 ng/mL [±1 standard deviation (SD)] pre-irradiation, 120 ± 13 ng/mL at 1 Gy; 242 ± 71 ng/mL at 2 Gy; 607 ± 54 at 5.5 Gy; and 1585 ± 351 at 6.5 Gy (±1 SD). There was an exponential increase in cfDNA concentration with radiation dose. Comparison of the monkey model with the mouse model and the Guskova model, developed using Chernobyl responder data, further demonstrated correlation across species, supporting a similar mechanism of action. The test is available commercially in a Clinical Laboratory Improvement Amendments (CLIA) ready form in the U.S. and the European Union. The remaining challenges include developing methods for further simplification of specimen processing and assay evaluation, as well as more accurate calibration of the triage category with cfDNA concentration cutoffs.

Prevalence and Genetic Characterization of Blastocystis in Sheep and Pigs in Shanxi Province, North China: From a Public Health Perspective.

Blastocystis is a common zoonotic intestinal protozoan and causes a series of gastrointestinal symptoms in humans and animals via the fecal-oral route, causing economic losses and posing public health problems. At present, the prevalence and genetic structure of Blastocystis in sheep and pigs in Shanxi province remains unknown. Thus, the present study collected 492 sheep fecal samples and 362 pig fecal samples from three representative counties in northern, central and southern Shanxi province for the detection of Blastocystis based on its SSU rRNA gene. The results showed that the overall prevalence of Blastocystis in the examined sheep and pigs were 16.26% and 14.09%, respectively. Sequences analyses showed that four known subtypes (ST5, ST10, ST14 and ST30) in sheep and two subtypes (ST1 and ST5) in pigs were detected in this study, with ST5 being the predominate subtype among the study areas. Phylogenetic analysis showed that the same subtypes were clustered into the same branch. This study reveals that sheep and pigs in Shanxi province are hosts for multiple Blastocystis subtypes, including the zoonotic subtypes (ST1 and ST5), posing a risk to public health. Baseline epidemiological data are provided that help in improving our understanding of the role of zoonotic subtypes in Blastocystis transmission.

Shape-dependent synthesis and photocatalytic degradation by Cu2O nanocrystals: Kinetics and photocatalytic mechanism.

In this study, Cu2O crystals with different morphologies were synthesized to investigate the effect of exposed crystalline facets on photocatalytic degradation efficiency. By adjusting the addition amount of PVP, different morphologies of Cu2O crystals were obtained, such as cubic, decahedral, octahedral, etc. XRD, SEM, and TEM characterizations were used to observe the properties of the synthesized Cu2O in terms of morphology, size, and lattice structure. The results showed that the octahedral cuprous oxide had the strongest photocatalytic degradation effect (78.3%). The study also explored the connection between different crystalline facets and MO microstructure, and the effect of crystalline facet selectivity on the pre-absorption and photocatalytic degradation of MO. Density Functional Theory (DFT) calculations were used to investigate the connection between the energy level structure of different crystalline facets of Cu2O and its photocatalytic activity. Finally, based on the experimental analysis and theoretical calculation, a new charge separation model on crystalline surface was proposed.

Molecular Detection and Genotyping of Enterocytozoon bieneusi in Beef Cattle in Shanxi Province, North China.

Enterocytozoon bieneusi is an intracellular pathogen that can parasitize humans and a variety of animals. The infection of E. bieneusi in most hosts is asymptomatic, but in immunocompromised individuals, it can lead to serious complications such as acute diarrhea, dehydration, and even death. However, no data on the prevalence and genotyping of E. bieneusi in beef cattle in Shanxi province are currently available. In this study, a total of 401 fecal samples were collected from beef cattle in farms from two representative counties­Qi county and Jishan county­in Shanxi province, north China. Nested PCR was applied to determine the prevalence and genotypes of E. bieneusi by amplifying and sequencing the internal transcribed spacer (ITS) regions of the rRNA gene. A total of 90 out of 401 samples were detected as E. bieneusi-positive, with 22.44% overall prevalence of E. bieneusi in beef cattle in Shanxi province. The highest prevalence of E. bieneusi was detected in calves (28.67%, 41/143) and male beef cattle (28.13%, 54/192). Statistical analysis revealed that the prevalence of E. bieneusi was significantly associated with gender and age factors (p < 0.05), but without any statistical difference among regions. Moreover, six known E. bieneusi genotypes (BEB4, BEB6, BEB8, J, I, and PigSpEb2) and two novel genotypes (designated CSC1 and CSC2) were identified by analysis of ITS sequences, and genotype I was the predominant genotype in these two counties. Phylogenetic analysis showed that five known genotypes and two novel genotypes were clustered into Group 2, but PigSpEb2 belonged to Group 1. To our knowledge, the present study demonstrated the presence and identified genotypes of E. bieneusi in beef cattle in Shanxi province for the first time, extending the data on prevalence and genotypes of E. bieneusi in beef cattle and providing baseline data for executing intervention measures to control it in the study regions.

Molecular Detection and Genotyping of Enterocytozoon bieneusi in Pigs in Shanxi Province, North China.

Enterocytozoon bieneusi is a common opportunistic intestinal pathogen that can cause acute diarrhea in immunosuppressed humans and animals. Though E. bieneusi has been widely detected in pigs around the world, little is known of its prevalence and genotype distribution in pigs in Shanxi province, north China. In this study, a total of 362 fecal samples were collected from pigs in three representative counties in north, south, and central Shanxi province, China. The prevalence and genotypes of E. bieneusi were investigated by nested PCR amplification of the ribosomal internal transcribed spacer (ITS) region of the ribosomal RNA (rRNA) gene. Overall, the prevalence of E. bieneusi in pigs in Shanxi province was 54.70% (198/362). Statistical analysis showed the difference in prevalence was statistically significant between regions (χ2 = 41.94, df = 2, P < 0.001) and ages (χ2 = 80.37, df = 1, P < 0.001). In addition, 16 genotypes of E. bieneusi were identified in this study by sequence analysis of the ITS region, including 15 known genotypes (EbpC, EbpA, EbpB, pigEb4, PigEBITS5, I, Henan-I, G, WildBoar 7, SH10, EbpD, CHC5, PigSpEb1, PigSpEb2, and CHG19) and one novel genotype (designated as PigSX-1). Phylogenetic analysis revealed that 14 known genotypes and the novel genotype were clustered into Group 1, whereas genotype I belonged to Group 2. To the best of our knowledge, this is the first report on the prevalence and genotypes of E. bieneusi in pigs in Shanxi province. These findings enrich the genetic diversity of E. bieneusi and provide the baseline data for the prevention and control of E. bieneusi in pigs in the study regions.

Molecular Identification and Genotyping of Enterocytozoon bieneusi in Sheep in Shanxi Province, North China.

Enterocytozoon bieneusi is a fungus-like protist that can cause malabsorption and diarrhea in sheep, other animals, and humans, threatening the development of animal husbandry and public health. To date, there are no data about the prevalence and genotypes of E. bieneusi in sheep in Shanxi Province, North China. In this study, 492 fecal samples were collected from sheep in three representative counties in northern, central, and southern Shanxi Province. Nested PCR amplification was performed to detect the prevalence and identify the genotypes of E. bieneusi based on the internal transcribed spacer (ITS) region of the rRNA gene. Overall, 168 of 492 examined samples were E. bieneusi-positive, with a prevalence of 34.2% (168/492). Significant differences in the prevalence of E. bieneusi were observed among the three sampled regions (χ2 = 95.859, df = 2, p < 0.001), but the differences in E. bieneusi prevalence were not statistically significant between different genders and age groups (p > 0.05). Sequence analysis showed that four known genotypes (BEB6, COS-I, CHS7, and CHC8) and one novel genotype (named SY-1) were identified. BEB6 was the prevalent genotype found within the three counties. Phylogenetic analysis revealed that the five genotypes observed in this study belong to Group 2. The present study reported the presence and genotypes of E. bieneusi infection in sheep in Shanxi Province for the first time, which enriches the knowledge of the genetic diversity of E. bieneusi and provides baseline data for the prevention and control of E. bieneusi infection in animals and humans.

Measuring Radiation Toxicity Using Circulating Cell-Free DNA in Prostate Cancer Patients.

BACKGROUND: After radiation therapy (RT), circulating plasma cell-free DNA (cfDNA) released in response to RT damage to tissue can be measured within hours. We examined for a correlation between cfDNA measured during the first week of therapy and early and late gastrointestinal (GI) and genitourinary (GU) toxicity. MATERIAL AND METHODS: Patients were eligible for enrollment if they planned to receive proton or photon RT for nonmetastatic prostate cancer in the setting of an intact prostate or after prostatectomy. Blood was collected before treatment and on sequential treatment days for the first full week of therapy. Toxicity assessments were performed at baseline, weekly during RT, and 6 months and 12 months after RT. Data were analyzed to examine correlations among patient-reported GI and GU toxicities. RESULTS: Fifty-four patients were evaluable for this study. Four (7%) and 3 (6%) patients experienced acute and late grade 2 GI toxicity, respectively. Twenty-two (41%) and 18 (35%) patients experienced acute and late grade 2 GU toxicity, respectively. No patients developed grade 3 or higher toxicity. Grade 2 acute GI toxicity, but not grade 2 acute GU toxicity, was significantly correlated with pre-RT cfDNA levels and on all days 1, 2, 3, 4, and 5 of RT (P < .005). Grade 2 late GI toxicity, but not GU toxicity, was significantly correlated with pre-RT cfDNA levels (P = .021). CONCLUSIONS: Based on this preliminary study, cfDNA levels can potentially predict the subset of patients destined to develop GI toxicity during prostate cancer treatment. Given that the toxicity profiles of the various fractionations and modalities are highly similar, the data support the expectation that cfDNA could provide a biological estimate to complement the dose-volume histogram. A test of this hypothesis is under evaluation in a National Cancer Institute-funded multi-institutional study.

Aggregation Kinetics of Polysorbate 80/m-Cresol Solutions: A Small-Angle Neutron Scattering Study.

Polysorbate 80 (PS80), a nonionic surfactant used in pharmaceutical formulation, is known to be incompatible with m-cresol, an antimicrobial agent for multi-dose injectable formulations. This incompatibility results in increased turbidity caused by micelle aggregation progressing over weeks or longer, where storage temperature, ionic strength, and component concentration influence the aggregation kinetics. Small-angle neutron scattering (SANS) analysis of PS80/m-cresol solutions over a pharmaceutically relevant concentration range of each component reveals the cause of aggregation, the coalescence mechanism, and aggregate structure. PS80 solutions containing m-cresol concentrations below ≈2.0 mg/mL and above ≈4.5 mg/mL are kinetically stable and do not aggregate over a 50 h period. At 5 mg/mL of m-cresol, the mixture forms a kinetically stable microemulsion phase, despite being well below the aqueous solubility limit of m-cresol. Solutions containing intermediate m-cresol concentrations (2.0-4.5 mg/mL) are unstable, resulting in aggregation, coalescence, and eventual phase separation. In unstable solutions, two stages of aggregate growth (nucleation and power-law growth) are observed at m-cresol concentrations at or below ≈3.6 mg/mL. At higher m-cresol concentrations, aggregates experience a third stage of exponential growth. A single kinetic model is developed to explain the stages of aggregate growth observed in both kinetic mechanisms. This work establishes the phase diagram of PS80/m-cresol solution stability and identifies component concentrations necessary for producing stable formulations.

Increased chemosensitivity via BRCA2-independent DNA damage in DSS1- and PCID2-depleted breast carcinomas.

Breast cancer, the most common malignancy among women, is closely associated with mutations in the tumor suppressor gene BRCA. DSS1, a component of the TRanscription-EXport-2 (TREX-2) complex involved in transcription and mRNA nuclear export, stabilizes BRCA2 expression. DSS1 is also related to poor prognosis in patients with breast cancer owing to the induction of chemoresistance. Recently, BRCA2 was shown to be associated with the TREX-2 component PCID2, which prevents DNA:RNA hybrid R-loop formation and transcription-coupled DNA damage. This study aimed to elucidate the involvement of these TREX-2 components and BRCA2 in the chemosensitivity of breast carcinomas. Our results showed that compared with that in normal breast tissues, DSS1 expression was upregulated in human breast carcinoma, whereas PCID2 expression was comparable between normal and malignant tissues. We then compared patient survival time among groups divided by high or low expressions of DSS1, BRCA2, and PCID2. Increased DSS1 expression was significantly correlated with poor prognosis in recurrence-free survival time, whereas no differences were detected in the high and low BRCA2 and PCID2 expression groups. We performed in vitro analyses, including propidium iodide nuclear staining, single-cell gel electrophoresis, and clonogenic survival assays, using breast carcinoma cell lines. The results confirmed that DSS1 depletion significantly increased chemosensitivity, whereas overexpression conferred chemoresistance to breast cancer cell lines; however, BRCA2 expression did not affect chemosensitivity. Similar to DSS1, PCID2 expression was also inversely correlated with chemosensitivity. These results strongly suggest that DSS1 and PCID2 depletion is closely associated with increased chemosensitivity via BRCA2-independent DNA damage. Together with the finding that DSS1 is not highly expressed in normal breast tissues, these results demonstrate that DSS1 depletion confers a druggable trait and may contribute to the development of novel chemotherapeutic strategies to treat DSS1-depleted breast carcinomas independent of BRCA2 mutations.

Mitigating background caused by extraneous scattering in small-angle neutron scattering instrument design.

Measurements, calculations and design ideas to mitigate background caused by extraneous scattering in small-angle neutron scattering (SANS) instruments are presented. Scattering includes processes such as incoherent scattering, inelastic scattering and Bragg diffraction. Three primary sources of this type of background are investigated: the beam stop located in front of the detector, the inside lining of the detector vessel and the environment surrounding the sample. SANS measurements were made where materials with different albedos were placed in all three locations. Additional measurements of the angle-dependent scattering over the angular range of 0.7π-0.95π rad were completed on 16 different shielding materials at five wavelengths. The data were extrapolated to cover scattering angles from π/2 to π rad in order to estimate the materials' albedos. Modifications to existing SANS instruments and sample environments to mitigate extraneous scattering from surfaces are discussed.

Preservative Induced Polysorbate 80 Micelle Aggregation.

Small angle neutron scattering (SANS) studies of a model pharmaceutical formulation reveal how formulation stability depends on the compatibility of individual components. Solutions of two common protein formulation excipients, polysorbate 80 (PS80), a nonionic surfactant that prevents aggregation, and m-cresol, an antimicrobial agent for multi-dose injectable formulations, are investigated. The addition of m-cresol to PS80 solutions leads to solution turbidity and irreversibly alters PS80 micelle morphology. This slow preservative-induced destabilization of PS80 micelles progresses over days or even weeks, which highlights the essential role that aggregation kinetics plays in preservative-surfactant interactions. The temperature-dependence of PS80 micelle growth kinetics is quantified by SANS in the presence of m-cresol. Aggregation is a two-step process, where initial formation of small aggregates is followed by a period of monotonic power-law growth, providing evidence for the mechanism. Total aggregate mass stays constant after initial aggregate formation, and addition of a pH-regulating citrate buffer dramatically accelerates aggregation kinetics.

Adsorption of non-ionic surfactant and monoclonal antibody on siliconized surface studied by neutron reflectometry.

The adsorption of monoclonal antibodies (mAbs) on hydrophobic surfaces is known to cause protein aggregation and degradation. Therefore, surfactants, such as Poloxamer 188, are widely used in therapeutic formulations to stabilize mAbs and protect mAbs from interacting with liquid-solid interfaces. Here, the adsorption of Poloxamer 188, one mAb and their competitive adsorption on a model hydrophobic siliconized surface is investigated with neutron scattering coupled with contrast variation to determine the molecular structure of adsorbed layers for each case. Small angle neutron scattering measurements of the affinity of Poloxamer 188 to this mAb indicate that there is negligible binding at these solution conditions. Neutron reflectometry measurements of the mAb show irreversible adsorption on the siliconized surface, which cannot be washed off with neat buffer. Poloxamer 188 can be adsorbed on the surface already occupied by mAb, which enables partial removal of some adsorbed mAb by washing with buffer. The adsorption of the surfactant introduces significant conformational changes for mAb molecules that remain on the surface. In contrast, if the siliconized surface is first saturated with the surfactant, no adsorption of mAb is observed. Competitive adsorption of mAb and Poloxamer 188 from solution leads to a surface dominantly occupied with surfactant molecules, whereas only a minor amount of mAb absorbs. These findings clearly indicate that Poloxamer 188 can protect against mAb adsorption as well as modify the adsorbed conformation of previously adsorbed mAb.

Environmental Response of 2D Thermal Cloak under Dynamic External Temperature Field.

As a typical representative of transformation thermodynamics, which is the counterpart of transformation optics, the thermal cloak has been explored extensively while most current research focuses on the structural design instead of adaptability and practicability in a dynamic environment. The evaluation of energy processes involved in the thermal cloak under dynamic conditions are also lacking, which is essential to the engineering application of this functional structure. In this paper, based on the dynamic environment of a sinusoidal form with ambient amplitude, distribution density, phase, and temperature difference as variables, we evaluated the cloaking performance and environmental response of a 2D thermal cloak. Considering the heat dissipation and energy loss in the whole procedure, local entropy production rate and response entropy were introduced to analyze the different influences of each environmental parameter on the cloaking system. Moreover, we constructed a series of comprehensive schemes to obtain the fitting equation as well as an appropriate scope to apply the thermal cloak. The results are beneficial to the novel use of the concept of entropy and valuable for further improving the working efficiency and potential engineering applications of the thermal cloak.

Circulating Cell-Free DNA Correlates with Body Integral Dose and Radiation Modality in Prostate Cancer.

PURPOSE: The RadTox assay measures circulating cell-free DNA released in response to radiotherapy (RT)-induced tissue damage. The primary objectives for this clinical trial were to determine whether cell-free DNA numbers measured by the RadTox assay are (1) correlated with body integral dose, (2) lower with proton RT compared with photon RT, and (3) higher with larger prostate cancer RT fields. PATIENTS AND METHODS: Patients planned to receive proton or photon RT for nonmetastatic prostate cancer in the setting of an intact prostate or postprostatectomy were eligible for the trial. Plasma was collected pre-RT and at 5 additional daily collection points beginning 24 hours after the initiation of RT. Data from 54 evaluable patients were analyzed to examine any correlations among RadTox scores with body-integral dose, RT modality (photon versus proton), and RT field size (prostate or prostate bed versus whole pelvis). RESULTS: Body integral dose was significantly associated with the peak post-RT RadTox score (P = .04). Patients who received photon RT had a significant increase in peak post-RT RadTox score (P = .04), average post-RT RadTox score (P = .04), and day-2 RadTox score (all minus the pre-RT values for each patient) as compared with patients who received proton RT. Field size was not significantly associated with RadTox score. CONCLUSION: RadTox is correlated with body integral dose and correctly predicts which patients receive proton versus photon RT. Data collection remains ongoing for patient-reported RT toxicity outcomes to determine whether RadTox scores are correlated with toxicity.

Competitive Surface Activity of Monoclonal Antibodies and Nonionic Surfactants at the Air-Water Interface Determined by Interfacial Rheology and Neutron Reflectometry.

Interfacial stresses can destabilize therapeutic formulations containing monoclonal antibodies (mAbs), which is proposed to be a result of adsorption and aggregation at the air-water interface. To increase protein stability, pharmaceutical industries add surfactants, such as Polysorbate 20 (PS20), into protein formulations to minimize mAb adsorption at the interface but rarely quantify this process. We determine that mAb adsorption in surfactant-free solutions creates a monolayer with significant viscoelasticity, which can influence measurements of bulk mAb solution viscosity. In contrast, PS20 absorption leads to an interface with negligible interfacial viscosity that protects the air-water interface from mAb adsorption. These studies were performed through a combined study of surface tensiometry, interfacial rheology, capillary viscometry, and neutron reflectometry to determine the surface activity of a model surfactant, PS20, and mAb system, which can be useful for the successful formulation developments of biotherapeutics.

Micellar Morphology of Polysorbate 20 and 80 and Their Ester Fractions in Solution via Small-Angle Neutron Scattering.

Surfactants are commonly used in therapeutic protein formulations in biopharmaceuticals to impart protein stability; however, their solution morphology and the role of the individual components in these structurally heterogeneous commercial grade surfactants at physiologically and pharmaceutically relevant temperatures have not been investigated systematically. The micellar morphologies of Polysorbate 20 and Polysorbate 80 and their primary components monoester fractions, as well as the diester fractions, are evaluated at 4, 22°C, 40°C, and 50°C using small-angle neutron scattering to determine the aggregation number, radius of gyration, core radius, critical micelle concentration, shell thickness, and shell hydration. The sizes and aggregation numbers of the diester fractions of PS20 above 80°C and PS80 above 50°C exhibit significant changes in shape. The analysis of the small-angle neutron scattering data of PS20 confirms that the critical micellar concentration of the monoester fraction is significantly higher at 4°C compared to the diester fraction and their original material, all-laurate PS20. Overall, these experiments identify the dominant components responsible for the temperature-dependent behavior of these surfactants in pharmaceutical protein formulations.

Radiation-induced tumor immunity in patients with non-small cell lung cancer.

BACKGROUND: Radiation-induced tumor immunity (RITI) influences primary tumor growth and development of metastases in preclinical cancer models with conventional radiotherapy. Antigen-specific immune responses have also been shown for prostate cancer treated with radiotherapy. We examined whether RITI can be induced in patients with non-small cell lung cancer (NSCLC) following proton radiotherapy. METHODS: Pre- and post-radiotherapy plasma samples from 26 patients with nonmetastatic NSCLC who received radiotherapy between 2010 and 2012 were evaluated by western blotting for IgG and IgM bands to assess RITI response to tumor antigens from lung cancer cell lines. Statistical analysis was used to evaluate any correlation among IgG or IgM and clinical outcomes. RESULTS: Twenty-one patients received proton therapy at 2 GyRBE/fraction (n = 17) or 6-12 Gy/fraction (n = 4); five received photon therapy at 2-2.5 GyRBE/fraction. Compared with the pretreatment baseline, new IgG or IgM binding was detected in 27% and 50% of patients, respectively. New IgG bands were detected in the 25-37 kD, 50-75 kD, and 75-100 kD ranges. New IgM bands were detected in the 20-25 kD, 25-37 kD, 37-50 kD, 50-75 kD, and 75-100 kD ranges. There was no difference in IgG and/or IgM RITI response in patients treated with photons versus protons, or in patients who received SBRT compared to standard fractionation (P > 0.05). There was no difference in overall survival, metastasis-free survival, or local control based on IgG and/or IgM RITI response (P > 0.05). CONCLUSION: RITI can be induced in patients with NSCLC through upregulated IgG and/or IgM. RITI response was not associated with proton versus photon therapy or with clinical outcomes in this small cohort and should be examined in a larger cohort in future studies.

Paediatric cerebral palsy prevalence and high-risk factors in Henan province, Central China.

OBJECTIVE: To evaluate the prevalence of, and risk factors for, cerebral palsy in Henan province, China. METHODS: The prevalence of cerebral palsy in children aged 0-6 years between September 2011 and September 2012 was investigated using a stratified-clustered-random sampling method. An age-, sex- , and residence-matched control group of typically developing children was recruited. Univariate analysis and multinomial logistic regression analysis were used to identify risk factors associated with cerebral palsy. RESULTS: The prevalence of cerebral palsy in Henan province was 2.37 per 1,000 live births. Risk factors included: moving into a newly painted room; complicating maternal diseases (infection, heart disease, hypertension, anaemia, diabetes, kidney disease) during pregnancy; high gravidity (> 3); foetal asphyxia; low birth-weight (< 2,500 g); and hypoxic-ischaemic encephalopathy. CONCLUSION: The prevalence of cerebral palsy in Henan province was 2.37 per 1,000 live births. Parents and clinicians should be aware of the risk factors for cerebral palsy.

Adsorption of polysorbate 20 and proteins on hydrophobic polystyrene surfaces studied by neutron reflectometry.

Understanding the adsorption of protein and surfactant molecules on hydrophobic surfaces is very important for storage stability and delivery of pharmaceutical liquid formulations as many commonly-used devices, such as drug containers and syringes, have hydrophobic surfaces. Neutron reflectometry is used here to investigate the structure information of the adsorption process of non-ionic surfactant (polysorbate 20) and proteins (monoclonal antibody (mAb) and lysozyme) on polystyrene surfaces. Thickness of adsorbed polysorbate 20 thin film is observed to be ≈21 Å, comparable to the radius of gyration of polysorbate 20 micelles in solution. Although no lysozyme adsorption is observed on the polystyrene surface in low solution pH condition, the mAb can be strongly absorbed on the polystyrene surface with a layer thickness of ≈145 Å. The mAb concentration near the surface is about 135 mg/ml significantly larger than the bulk protein concentration. The differences in adsorption behavior are attributed to different protein interactions with a hydrophobic surface. Further, both surfactants and proteins adsorbed on the polystyrene surfaces can not be rinsed off using pure water.

DcR3, a new biomarker for sepsis, correlates with infection severity and procalcitonin.

Early diagnosis of sepsis is critical for successful treatment. The clinical value of DcR3 in early diagnosis of sepsis was determined in a dynamic follow-up study. Alterations in plasma levels of DcR3, PCT, CRP, and IL-6 were measured by ELISA and compared among patients with sepsis (n = 134), SIRS (n = 60) and normal adults (n = 50). Correlations and dynamic patterns among the biomarkers, APACHE II scores, clinical outcomes, and pathogens were also examined. Plasma DcR3 was significantly increased in sepsis compared to SIRS and normal adults (median 3.87 vs. 1.28 and 0.17 ng/ml). The elevated DcR3 could be detected in 97.60% sepsis patients 1-2 days prior to the result of blood culture reported. For diagnosis of sepsis, the sensitivity was 97.69% and specificity 98.04%; and for differential diagnosis of sepsis from SIRS, the sensitivity was 90.77% and specificity 98.40%. DcR3 level was positively correlated with severity of sepsis (rs = 0.82). In 41 patients who died of sepsis, DcR3 elevated as early as 1-2 days before blood culture and peaked on day 3 after blood culture performed. In 90% of sepsis patients, the dynamic alteration pattern of DcR3 was identical to that of PCT, while pattern of 10% patients differed in which clinical data was consistent with DcR3. In 13% sepsis patients, while PCT remained normal, DcR3 levels were at a high level. DcR3 levels had no difference among various pathogens infected. DcR3, a new biomarker, will aid in early diagnosis of sepsis and monitoring its outcome, especially when sepsis patients were PCT negative.