bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combination of recombinant factor VIIa and fibrinogen corrects clot formation in primary immune thrombocytopenia at very low platelet counts
Authors: Larsen Ole H. , Stentoft Jesper , Radia Deepti , Ingerslev Jørgen , Sørensen Benny 
Published: November 2012

SummaryHaemostatic treatment modalities alternative to platelet transfusion are desirable to control serious acute bleeds in primary immune thrombocytopenia (ITP). This study challenged the hypothesis that recombinant activated factor VII (rFVIIa) combined with fibrinogen concentrate may correct whole blood (WB) clot formation in ITP. Blood from ITP patients (n = 12) was drawn into tubes containing 3·2% citrate and corn trypsin inhibitor 18·3 μg/ml. WB [mean platelet count 22 × 109/l (range 0–42)] was spiked in vitro with buffer, donor platelets (+40 × 109/l), rFVIIa (1 or 4 μg/ml), fibrinogen (1 or 3 mg/ml), or combinations of rFVIIa and fibrinogen. Coagulation profiles were recorded by tissue factor (0·03 pmol/l) activated thromboelastometry. Coagulation in ITP was characterized by a prolonged clotting time (CT, 1490 s (mean)) and a low maximum velocity (MaxVel, 3·4 mm × 100/s) and maximum clot firmness (MCF, 38·2 mm). Fibrinogen showed no haemostatic effect, whereas rFVIIa reduced the CT and increased the MaxVel. The combination of fibrinogen and rFVIIa revealed a significant synergistic effect, improving all parameters (CT 794 s, MaxVel 7·9 mm × 100/s, MCF 50·7 mm) even at very low platelet counts. These data suggest that rFVIIa combined with fibrinogen corrects the coagulopathy of ITP even at very low platelet counts, and may represent an alternative to platelet transfusion.
Using longitudinal data from the Health Survey for England to resolve discrepancies in thresholds for haemoglobin in older adults
Authors: Mindell Jennifer , Moody Alison , Ali Ayesha , Hirani Vasant 
Published: November 2012

SummaryAnaemia increases with age and is common among older people. Due to its relationship with morbidity and mortality, accurate diagnosis is important. Thresholds defining the diagnosis of anaemia have been the subject of considerable scientific debate, with both higher and lower cut‐offs proposed. High haemoglobin is also a health risk in some but not all studies. Using nationally representative data of 5,329 adults aged 65 + years (Health Survey for England 1998, 2005, 2006), linked to administrative mortality data, this paper describes the relationship between haemoglobin levels and mortality, adjusted for age and other confounders. Among men, a reverse J shaped relationship was observed: relative to the modal group (140–149 g/l), those with ‘mild anaemia’ of 120–129 g/l haemoglobin had a 56% (95% confidence interval 24–96%) greater mortality hazard, and those with ‘severe anaemia’, haemoglobin <120 g/l, had an 87% (39–153%) greater hazard. At the other end of the range, those with haemoglobin ≥160 g/l had 32% (2–70%) greater mortality hazard. Haemoglobin levels in women showed a similar but smaller, non‐significant pattern: hazard ratio 1·32 (0·91–1·92) for severe anaemia (<110 g/l), and 1·30 (0·95–1·79) for high haemoglobin (≥150 g/l). This research supports the use of the World Health Organization thresholds (130 g/l for men, 120 g/l for women).
Improved outcome for children with non‐high risk acute lymphoblastic leukaemia after using an ALL IC‐BFM 2002‐based protocol in Shanghai, China
Authors: Gao Yi‐Jin , Qian Xiao‐Wen , Lu Feng‐Juan , Zhai Xiao‐Wen , Wang Hong‐Sheng , Li Jun 
Published: November 2012

SummaryWe report the outcome of 92 non‐high risk children with acute lymphoblastic leukaemia (ALL) following a Berlin‐Frankfürt‐Münster (BFM) Intercontinental ALL ‐based protocol. Compared with a matched historical control group, we found a lower incidence of treatment‐related early death (1·2% vs. 10·9%, P = 0·015), a higher 6‐year event‐free survival (75·4 ± 4·9% vs. 58·2 ± 6·7%, P = 0·02), reduced total in‐hospital costs per person (US $) (10267·0 vs. 18331·0, P < 0·001) and fewer total in‐hospital days (164 vs. 296, P < 0·001). This ALL‐BFM based protocol was quite tolerable in our institution and will be extended to high‐risk patients.
Food Deprivation and Restriction During late Gestation Affect the Sexual Behavior of Postpartum Female Meadow Voles, Microtus pennsylvanicus
Authors: Sabau Ramona M. , Ferkin Michael H. 
Published: November 2012

AbstractIn many species of small mammals, including meadow voles, Microtus pennsylvanicus, females come into postpartum estrus (PPE) within 12–24 h of giving birth, allowing them to mate and become pregnant while raising the current litter. PPE females show increases in attractivity, proceptivity, and receptivity, the three components of sexual behavior, relative to females not in PPE. Several studies have shown that food deprivation and restriction reduce attractivity, proceptivity, and receptivity of females not in PPE. We tested the hypothesis that food deprivation and restriction during late gestation cause deficits and decrease the attractivity, proceptivity, and receptivity of females when they enter PPE. Our data support the hypothesis. On day 1 of lactation, females that were food deprived and food restricted produced scent marks that were significantly less attractive as those produced by control PPE females. Food deprivation but not food restriction caused females to no longer display significant preferences for the scent marks of males over those of females (proceptivity). Food deprivation and food restriction were sufficient to induce females to become significantly less sexually receptive than control females. Eleven of 12 control PPE females mated, 4 of 12 food‐restricted females mated, and 3 of 12 food‐deprived females mated. Dams facing food deprivation or restriction during late gestation may have to balance the benefits of mating during PPE with the increased costs associated with getting pregnant while they are lactating.
Acetate Metabolism During Hemodialysis
Authors: Weiner Michael W. 
Published: November 2012

ABSTRACTWe infused acetate into normal human subjects and performed kinetic analysis of the plasma and urine values obtained before, during, and after the infusion. The data were best fitted by a first‐order elimination process with a mean metabolic clearance rate of 2.3 L/min. Gotch and Sargent had previously suggested that during dialysis, acetate metabolism was zero order. We performed kinetic modeling of acetate concentrations during dialysis. The data were best fitted to a Michaelis‐Menton model (i.e., first‐order metabolism at low concentrations and saturated at high concentrations). The mean Km for acetate in the dialysis patients was 8.5 mM and the mean Vmax was 18 mmol/min. Patients with a Vmax less than 7 mmol/min usually had a fall in plasma bicarbonate during dialysis while patients with a Vmax greater than 14 mmol/min usually had a rise in bicarbonate during dialysis. It is concluded that during high‐surface‐area dialysis, the capacity for acetate metabolism will affect acid‐base homeostasis. Kinetic modeling will be useful to define acetate‐intolerant patients and may be used to predict patients who will benefit from bicarbonate hemodialysis.
The Effect of Acetate and Bicarbonate Dialysis on Orthostatic Blood Pressure Regulation
Authors: Landwehr D. M. , Okusa M. D. 
Published: November 2012

ABSTRACTDialysis‐induced hypotension is probably due to multiple factors which reduce cardiac output and peripheral vascular resistance. That acetate, used in dialysate as a source of bicarbonate, may be one of these factors is suggested from several studies which show improved blood pressure regulation with bicarbonate‐containing dialysate. We have further examined this hypothesis by comparing supine and standing blood pressure changes in nine stable patients during dialysis with acetate or bicarbonate solutions. Although mean weight changes were not different, standing blood pressure was lower after acetate dialysis. Such a hypotensive effect of acetate could result from depression of the force of myocardial contraction and/or from a reduction in peripheral vascular resistance.
Effect of Bicarbonate‐Containing Dialysate on Chronic Hemodialysis Patients: A Comparative Study
Authors: Man N. K. , Fournier G. , Thireau P. , Gaillard J. L. , Funck‐Brentano J.‐L. 
Published: November 2012

ABSTRACTChanges in pH and blood gases were studied during hemodialysis with both acetate and bicarbonate dialysates. During acetate dialysis, Pao2 and Paco2 decreased significantly (P < 0.05) from 101 ± 2 to 93 ± 3 mmHg and from 34.4 ± 1.0 to 31.8 ± 0.9 mmHg, respectively, whereas during bicarbonate dialysis neither parameter changed significantly. The final pH was 7.45 ± 0.01 during acetate dialysis and 7.50 ± 0.02 during bicarbonate dialysis. Plasma bicarbonate rose immediately and progressively from 18.9 ± 0.8 to 26.8 ± 0.9 mmol/L with bicarbonate dialysis, whereas the increase was moderate, from 19.6 ± 0.6 to 22.3 ± 0.5 mmol/L, with acetate dialysis. These data indicate that dialysis‐induced hypoxemia was prevented and correction of acidosis was more adequate with bicarbonate dialysis. During a two‐year period on bicarbonate dialysis, total cholesterol, HDL‐cholesterol, and triglycerides did not change significantly when compared to acetate dialysis. The most striking change was the increased tolerance to dialysis with bicarbonate dialysis, which included a 50% reduction in hypotensive episodes and muscle cramps and an almost complete absence of headache, nausea, and vomiting.
A Modified Obesity Proneness Model Predicts Adolescent Weight Concerns and Inability to Self‐Regulate Eating
Authors: Nickelson Jen , Bryant Carol A. , McDermott Robert J. , Buhi Eric R. , DeBate Rita D. 
Published: November 2012

BACKGROUND: The prevalence of obesity among high school students has risen in recent decades. Many high school students report trying to lose weight and some engage in disordered eating to do so. The obesity proneness model suggests that parents may influence their offspring's development of disordered eating. This study examined the viability of a modified obesity proneness model in a high school population.METHODS: Cross‐sectional survey data from a random cluster sample of 1533 students in grades 9–12 from a Florida school district were analyzed using structural equation modeling. Variables included adolescents' weight concerns; inability to self‐regulate eating; and perceptions about maternal comments about adolescents' weight, restrictive feeding practices, and maternal weight‐related concern and values.RESULTS: All the model's originally proposed relationships were statistically significant, for example perceived maternal weight comments were associated with adolescents' weight concerns (β = 0.64; p < .0001), and perceived maternal restrictive feeding practices were associated with adolescents' inability to self‐regulate eating (β = 0.22; p < .001).CONCLUSION: Some points of intervention should be subjected to empirical study. These interventions should give mothers guidance about appropriate feeding practices and discourage mothers from making weight‐related comments to their offspring. Together, as 1 component of a multilevel intervention, these behaviors may help prevent disordered eating and obesity.
Simulation Based Optimization for World Line Card Production System
Authors: APAK Sinan , ERCAN Sami 
Published: November 2012

Simulation based decision support system is one of the commonly used tool to examine complex production systems. The simulation approach provides process modules which can be adjusted with certain parameters by using data relatively easily obtainable in production process. World Line Card production system simulation is developed to evaluate the optimality of existing production line via using discrete event simulation model with variaty of alternative proposals. The current production system is analysed by a simulation model emphasizing the bottlenecks and the poorly utilized production line. Our analysis identified some improvements and efficient solutions for the existing system.
Application of Response Surface Methodology (RSM) for Optimization of Operating Parameters and Performance Evaluation of Cooling Tower Cold Water Temperature
Authors: RAMAKRISHNAN Ramkumar , ARUMUGAM Ragupathy 
Published: November 2012

Performance of the coolig tower was analysed with various operating parameters and find the minimum cold water temperature. In this study, optimization of operating parameters was investigated. An experimental design was carried out based on central composite design(CCD) with response surface methodology(RSM). This paper presents optimum operating parameters and the minimum cold water temperature using RSM method. The RSM was used to evaluate the effects of operating variables and their interaction towards the attainment of their optimum conditions. Based on statistical analysis, water flow, air flow, hot water temperature and packing height were high significant on cold water temperature, with very low probability values(<0.0001). The optimum operating parameters predicted using RSM method and confirmed through experiment.
Emergence of OXA-48 and OXA-181 Carbapenemases among Enterobacteriaceae in South Africa and Evidence of
In Vivo
Selection of Colistin Resistance as a Consequence of Selective Decontamination of the Gastrointestinal Tract
Authors: Brink Adrian J. , Coetzee Jennifer , Corcoran Craig , Clay Cornelis G. , Hari-Makkan Danusha , Jacobson Rachael K. , Richards Guy A. , Feldman Charles , Nutt Louise , van Greune Johan , Deetlefs J. D. , Swart Karin , Devenish Lesley , Poirel Laurent , Nordmann Patrice 
Published: November 2012

ABSTRACT

This study reports on the emergence of OXA-48-like carbapenemases among isolates of
Enterobacteriaceae
in South Africa. In addition, the emergence during therapy of a colistin-resistant OXA-181-producing
Klebsiella pneumoniae
isolate was documented following selective digestive tract decontamination with oral colistin, which is therefore strongly discouraged.
Characterization of Hepatitis C Virus Recombinants with Chimeric E1/E2 Envelope Proteins and Identification of Single Amino Acids in the E2 Stem Region Important for Entry
Authors: Carlsen Thomas H. R. , Scheel Troels K. H. , Ramirez Santseharay , Foung Steven K. H. , Bukh Jens 
Published: November 2012

ABSTRACT

The hepatitis C virus (HCV) envelope proteins E1 and E2 play a key role in host cell entry and represent important targets for vaccine and drug development. Here, we characterized HCV recombinants with chimeric E1/E2 complexes
in vitro
. Using genotype 1a/2a JFH1-based recombinants expressing 1a core-NS2, we exchanged E2 with functional isolate sequences of genotypes 1a (alternative isolate), 1b, and 2a. While the 1a-E2 exchange did not impact virus viability, the 2a-E2 recombinant was nonviable. After E2 exchange from three 1b isolates, long delays were observed before spread of infection. For recovered 1b-E2 recombinants, single E2 stem region amino acid changes were identified at residues 706, 707, and 710. In reverse genetic studies, these mutations increased infectivity titers by ∼100-fold, apparently without influencing particle stability or cell binding although introducing slight decrease in particle density. In addition, the 1b-E2 exchange led to a decrease in secreted core protein of 25 to 50%, which was further reduced by the E2 stem region mutations. These findings indicated that compensatory mutations permitted robust infectious virus production, without increasing assembly/release. Studies of E1/E2 heterodimerization showed no differences in intracellular E1/E2 interaction for chimeric constructs with or without E2 stem region mutations. Interestingly, the E2 stem region mutations allowed efficient entry, which was verified in 1a-E1/1b-E2 HCV pseudoparticle assays. A CD81 inhibition assay indicated that the mutations influenced a late step of the HCV entry pathway. Overall, this study identified specific amino acids in the E2 stem region of importance for HCV entry and for production of infectious virus particles.
Human Papillomavirus E7 Induces Rereplication in Response to DNA Damage
Authors: Fan Xueli , Liu Yingwang , Heilman Susan A. , Chen Jason J. 
Published: November 2012

ABSTRACT

Human papillomavirus (HPV) infection is necessary but not sufficient for cervical carcinogenesis. Genomic instability caused by HPV allows cells to acquire additional mutations required for malignant transformation. Genomic instability in the form of polyploidy has been demonstrated to play an important role in cervical carcinogenesis. We have recently found that HPV-16 E7 oncogene induces polyploidy in response to DNA damage; however, the mechanism is not known. Here we present evidence demonstrating that HPV-16 E7-expressing cells have an intact G
2
checkpoint. Upon DNA damage, HPV-16 E7-expressing cells arrest at the G
2
checkpoint and then undergo rereplication, a process of successive rounds of host DNA replication without entering mitosis. Interestingly, the DNA replication initiation factor Cdt1, whose uncontrolled expression induces rereplication in human cancer cells, is upregulated in E7-expressing cells. Moreover, downregulation of Cdt1 impairs the ability of E7 to induce rereplication. These results demonstrate an important role for Cdt1 in HPV E7-induced rereplication and shed light on mechanisms by which HPV induces genomic instability.
Increasing Expression of MicroRNA 181 Inhibits Porcine Reproductive and Respiratory Syndrome Virus Replication and Has Implications for Controlling Virus Infection
Authors: Guo Xue-kun , Zhang Qiong , Gao Li , Li Ning , Chen Xin-xin , Feng Wen-hai 
Published: November 2012

ABSTRACT

Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important viral pathogens in the swine industry. Emerging evidence indicates that the host microRNAs (miRNAs) are involved in host-pathogen interactions. However, whether host miRNAs can target PRRSV and be used to inhibit PRRSV infection has not been reported. Recently, microRNA 181 (miR-181) has been identified as a positive regulator of immune response, and here we report that miR-181 can directly impair PRRSV infection. Our results showed that delivered miR-181 mimics can strongly inhibit PRRSV replication
in vitro
through specifically binding to a highly (over 96%) conserved region in the downstream of open reading frame 4 (ORF4) of the viral genomic RNA. The inhibition of PRRSV replication was specific and dose dependent. In PRRSV-infected Marc-145 cells, the viral mRNAs could compete with miR-181-targeted sequence in luciferase vector to interact with miR-181 and result in less inhibition of luciferase activity, further demonstrating the specific interactions between miR-181 and PRRSV RNAs. As expected, miR-181 and other potential PRRSV-targeting miRNAs (such as miR-206) are expressed much more abundantly in minimally permissive cells or tissues than in highly permissive cells or tissues. Importantly, highly pathogenic PRRSV (HP-PRRSV) strain-infected pigs treated with miR-181 mimics showed substantially decreased viral loads in blood and relief from PRRSV-induced fever compared to negative-control (NC)-treated controls. These results indicate the important role of host miRNAs in modulating PRRSV infection and viral pathogenesis and also support the idea that host miRNAs could be useful for RNA interference (RNAi)-mediated antiviral therapeutic strategies.
Cyclin T1 and CDK9 T-Loop Phosphorylation Are Downregulated during Establishment of HIV-1 Latency in Primary Resting Memory CD4+T Cells
Authors: Budhiraja Sona , Famiglietti Marylinda , Bosque Alberto , Planelles Vicente , Rice Andrew P. 
Published: November 2012

ABSTRACTP-TEFb, a cellular kinase composed of Cyclin T1 and CDK9, is essential for processive HIV-1 transcription. P-TEFb activity is dependent on phosphorylation of Thr186 in the CDK9 T loop. In resting CD4+T cells which are nonpermissive for HIV-1 replication, the levels of Cyclin T1 and T-loop-phosphorylated CDK9 are very low but increase significantly upon cellular activation. Little is known about how P-TEFb activity and expression are regulated in resting central memory CD4+T cells, one of the main reservoirs of latent HIV-1. We used anin vitroprimary cell model of HIV-1 latency to show that P-TEFb availability in resting memory CD4+T cells is governed by the differential expression and phosphorylation of its subunits. This is in contrast to previous observations in dividing cells, where P-TEFb can be regulated by its sequestration in the 7SK RNP complex. We find that resting CD4+T cells, whether naïve or memory and independent of their infection status, have low levels of Cyclin T1 and T-loop-phosphorylated CDK9, which increase upon activation. We also show that the decrease in Cyclin T1 protein upon the acquisition of a memory phenotype is in part due to proteasome-mediated proteolysis and likely also to posttranscriptional downregulation by miR-150. We also found that HEXIM1 levels are very low inex vivo- andin vitro-generated resting memory CD4+T cells, thus limiting the sequestration of P-TEFb in the 7SK RNP complex, indicating that this mechanism is unlikely to be a driver of viral latency in this cell type.
Critical Roles of Glucocorticoid-Induced Leucine Zipper in Infectious Bursal Disease Virus (IBDV)-Induced Suppression of Type I Interferon Expression and Enhancement of IBDV Growth in Host Cells via Interaction with VP4
Authors: Li Zhonghua , Wang Yongqiang , Li Xiang , Li Xiaoqi , Cao Hong , Zheng Shijun J. 
Published: November 2012

ABSTRACTInfectious bursal disease (IBD) is an acute, highly contagious, and immunosuppressive avian disease caused by IBD virus (IBDV). Although IBDV-induced immunosuppression has been well established, the underlying exact molecular mechanism for such induction is not very clear. We report here the identification of IBDV VP4 as an interferon suppressor by interaction with the glucocorticoid-induced leucine zipper (GILZ) in host cells. We found that VP4 suppressed the expression of type I interferon in HEK293T cells after tumor necrosis factor alpha (TNF-α) treatment or Sendai virus (SeV) infection and in DF-1 cells after poly(I·C) stimulation. In addition, the VP4-induced suppression of type I interferon could be completely abolished by knockdown of GILZ by small interfering RNA (siRNA). Furthermore, knockdown of GILZ significantly inhibited IBDV growth in host cells, and this inhibition could be markedly mitigated by anti-alpha/beta interferon antibodies in the cell cultures (P< 0.001). Thus, VP4-induced suppression of type I interferon is mediated by interaction with GILZ, a protein that appears to inhibit cell responses to viral infection.