Miracle-dz/UniFAR-FTUs huggingface dataset:
Cell Surface Delivery of TRAIL Strongly Augments the Tumoricidal Activity of T Cells

Purpose: Adoptive T-cell therapy generally fails to induce meaningful anticancer responses in patients with solid tumors. Here, we present a novel strategy designed to selectively enhance the tumoricidal activity of T cells by targeted delivery of TNF-related apoptosis-inducing ligand (TRAIL) to the T-cell surface. Experimental Design: We constructed two recombinant fusion proteins, anti-CD3:TRAIL and K12:TRAIL. Tumoricidal activity of T cells in the presence of these fusion proteins was assessed in solid tumor cell lines, primary patient-derived malignant cells, and in a murine xenograft model. Results: When added to T cells, K12:TRAIL and anti-CD3:TRAIL selectively bind to the T-cell surface antigens CD3 and CD7, respectively, leading to cell surface accretion of TRAIL. Subsequently, anti-CD3:TRAIL and K12:TRAIL increased the tumoricidal activity of T cells toward cancer cell lines and primary patient-derived malignant cells by more than 500-fold. Furthermore, T-cell surface delivery of TRAIL strongly inhibited tumor growth and increased survival time of xenografted mice more than 6-fold. Conclusions: Targeted delivery of TRAIL to cell surface antigens of T cells potently enhances the tumoricidal activity of T cells. This approach may be generally applicable to enhance the efficacy of adoptive T-cell therapy. Clin Cancer Res; 17(17); 5626–37. ©2011 AACR.
Ibuprofen Decreases Cytokine-Induced Amyloid Beta Production in Neuronal Cells

Trying to decrease the production of Amyloid beta (Abeta) has been envisaged as a promising approach to prevent neurodegeneration in Alzheimer's disease (AD). A chronic inflammatory reaction with activated microglia cells and astrocytes is a constant feature of AD. The participation of the immune system in the disease process is further documented in several retrospective clinical studies showing an inverse relationship between the prevalence of AD and nonsteroidal anti-inflammatory drug (NSAID) therapy. Previously, we demonstrated that the combination of the proinflammatory cytokines TNFalpha with IFNgamma induces the production of Abeta-42 and Abeta-40 in human neuronal cells. In the present study, the neuronal cell line Sk-n-sh was incubated for 12 h with the cyclooxygenase inhibitor ibuprofen and subsequently stimulated with the cytokines TNFalpha and IFNgamma. Ibuprofen treatment decreased the secretion of total Abeta in the conditioned media of cytokine stimulated cells by 50% and prevented the accumulation of Abeta-42 and Abeta-40 in detergent soluble cell extracts. Viability of neuronal cells measured by detection of apoptosis was neither influenced by ibuprofen nor by cytokine treatment. The reduction in the production of Abeta by ibuprofen was presumably due to a decreased production of betaAPP, which in contrast to the control proteins M2 pyruvate kinase, beta-tubulin and the cytokine inducible ICAM-1 was detected at low concentration in ibuprofen treated cells. The data demonstrate a possible mechanism how ibuprofen may decrease the risk and delay the onset of AD.
Mutation in the beta adducin subunit causes tissue-specific damage to myogenic tone

Background Damage to renal artery myogenic tone is universally associated with progressive kidney damage. Recently, we have observed that mutations in the beta adducin subunit are associated with proteinuria in the Milan rat. Because of the role of adducin as a component of the cytoskeleton we hypothesized that this mutation may be associated with changes in myogenic tone. Methods and results Congenic rats were generated with beta adducin subunit mutation (NB rats) and compared with a previously studied rat model with alpha adducin subunit mutation (NAs rats). Blood pressure and urinary protein excretion were studied at two time points: 6 weeks and 4 months of age, and at these time points, small renal, middle cerebral and skeletal (cremaster) arteries were isolated and studied using pressure myography. Agonist-induced vasoconstriction was not different between the two groups at any age. However, myogenic tone in renal arteries was significantly damaged in the NB rat compared to its NAs counterpart and this was associated with a decrease in vascular distensibility. There was a smaller reduction in myogenic tone in the middle cerebral arteries from the NB rat, whereas in the skeletal arteries there was no difference between the two strains. In the NB rat, this tissue-specific damage to myogenic tone was associated with progressive proteinuria despite lower blood pressure than the NAs rat. Conclusions Mutations in the beta subunit of the adducin protein result in damage to renal artery myogenic tone and this is associated with renal damage as manifest by proteinuria.
HYDROGEN PEROXIDE PHOTOLYSIS WITH DIFFERENT UV LIGHT SOURCES INCLUDING A NEW UV-LED LIGHT SOURCE

Hydrogen peroxide 0.1% was photolyzed using 17W low pressure mercury arc lamp and 125 W high pressure mercury arc lamp. The decomposition kinetics was followed through the pseudofirst order kinetics and different conditions of temperature and pH were explored. H2O2 0.1% was also photolyzed at 360 nm through a new UV-LED 3W light source using a flow reactor. The kinetics rate constant achieved with the UV-LED photolysis is at least one order of magnitude lower than that achieved with the low pressure mercury arc lamp. Other drawbacks of the UV-LED photolysis were evidenced.
Characteristic‐mixed covolume methods for advection‐dominated diffusion problems

Characteristic‐mixed covolume methods for time‐dependent advection‐dominated diffusion problems are developed and studied. The diffusion term in these problems is discretized using covolume methods applied to the mixed formulation of the problems on quadrilaterals, and the temporal differentiation and advection terms are treated by characteristic tracking schemes. Three characteristic tracking schemes are studied in the context of mixed covolume methods: the modified method of characteristics, the modified method of characteristics with adjusted advection, and the Eulerian–Lagrangian localized adjoint method. The proposed methods preserve the conceptual and computational merits of both characteristics‐based schemes and the mixed covolume methods. Existence and uniqueness of a solution to the discrete problem arising from the methods is shown. Stability and convergence properties of these methods are also obtained; unconditionally stable results and error estimates of optimal order are established. Copyright © 2006 John Wiley & Sons, Ltd.
Physicians' Perceptions and Uses of Commercial Drug Information Sources

Abstract Data were collected from physicians attending a medical conference. This exploratory study was primarily interested in two areas. First, the investigators were interested in better understanding physicians' responses to different promotional tactics typically used by the pharmaceutical industry. Pharmaceutical representatives were most useful, followed by drug samples and infomercials in medical journals. Direct mail, promotional faxes, and promotional products were used less by physicians. Second, the investigators were interested in learning what information sources influenced physicians' drug choices. Physicians were primarily influenced by their prior experience with a drug, then by drug compendiums, and journal articles. Physicians were also influenced by information provided by the industry and other factors, like the drug's price and their patients' financial situations. Managerial implications for marketing to physicians and ideas for future research are discussed.
Effect of black tea drinking on blood lipids, blood pressure and aspects of bowel habit

Thirty-one men (47 (SD 14) years) and thirty-four women (35 (SD 13) years) took part in a 4-week randomized cross-over trial to compare the effect of six mugs of black tea daily v. placebo (water, caffeine, milk and sugar) on blood lipids, bowel habit and blood pressure, measured during a run-in period and at the end of weeks 2, 3 and 4 of the test periods. Compliance was established by adding a known amount of p–aminobenzoic acid (PABA) to selected tea bags, and then measuring its excretion in urine. Mean serum cholesterol values during run-in, placebo and on tea drinking were 5·67 (SD 1·05), 5·76 (SD 1·11) and 5·69 (SD 1·09)mmol/l (P=0·16). There were also no significant changes in diet, LDL-cholesterol, HDL-cholesterol, triacylglycerols, and blood pressure in the tea intervention period compared with placebo. Compared with placebo, stool consistency was softened with tea (P=0·04), and no other differences were found in bowel habit. Results were unchanged when fifteen ‘non-compliers’, whose PABA excretion indicated that fewer than six tea bags had been used, were excluded from the analysis, and when differences between run-in and tea periods were considered separately for those who were given tea first or second.
Isolation and identification of stem cells in different subtype of cartilage tissue

Background: Cartilage tissue engineering provided a promising therapy for the repair of cartilage defects, and seeding cells play a vital role in cartilage regeneration. Chondrocytes and bone marrow-derived mesenchymal stem cells (BMSCs) were reported to be the ideal seeding cells, but ‘dedifferentiation’ and ‘unstable phenotype’ of tissue-engineered cartilage constructed by the two cell type hamper their clinical application. Recently, cartilage tissue was reported to possess a stem cell population, which may be a more superior cell source in cartilage tissue engineering. Methods: In current study, we isolated a cell population from different subtype of cartilage tissue via a differential adhesion assay to fibronectin. Results: Flow cytometry analysis demonstrates the cell lines expressed mesenchyme stem cell positive surface marker such as CD29 and CD90. Meanwhile, the cells are highly proliferative and multipotent. Reverse transcription–PCR detection showed the cell population expressed osteogenic and adipogenic differentiation under different induction conditions. More interesting, monolayer cells underwent chondrogenic differentiation in the presence of dexamethasone and insulin-like growth factor 1. In addition, the expression of chondrogenic genes in cartilage-derived stem cells (CSCs) was higher than those in BMSCs. Conclusion: CSC may become an ideal seeding cell in cartilage tissue engineering, owing to its stemness and chondrogenic characteristics.
Costs and Cost-Effectiveness in Hip and Knee Replacements: A Prospective Study

Abstract The extensive benefits of the total hip (THA) and knee (TKA) replacements are well documented, but surprisingly little is known about their economics. We assessed costs, cost-effectiveness (C/E), and patient-related C/E variances in THA and TKA from data on 276 THA and 176 TKA patients. Patients with primary arthrosis, primary operation, and total joint replacement were recruited from seven hospitals between March 1991 and June 1992. Their use of health and other welfare services together with health-related quality of life (HRQoL) were measured before the surgery and at 6, 12, and 24 months postoperatively. HRQoL was assessed by the 15D, a 15-dimensional HRQoL instrument, and the Nottingham Health Profile. Costs were assessed from questionnaire responses, the Finnish Hospital Discharge Register, and Finnish Arthroplasty Register. Total hospital costs per patient were 45,000 FIM (US $10,500) for THA and 49,600 FIM (US $11,500) for TKA. Prosthesis costs comprised 21 % of these costs in THA and 24% in TKA. On average, hip patients gained more in terms of HRQoL, and the operations were more cost-effective. The C/E ratio for younger (« 60 years) knee patients did not differ from those in all age groups of hip patients, whereas TKAs in those over 60 years had a worse C/E ratio compared with all other patient subgroups. It was concluded that allocation efficiency can be improved by considering not only the intervention but also patient characteristics such as age. Indeed, the C/E ratio varied more across age groups of knee patients than between average THA and TKA patients.
Phosphorylation of the High Molecular Weight Neurofilament Protein (NF-H) by Cdk5 and p35*

The high molecular weight neurofilament protein (NF-H) is highly phosphorylated in the axon. The phosphorylation sites have been identified as KSP (Lys-Ser-Pro) repeats in the tail domain of NF-H. These KSP sequences are present more than 50 times in the NF-H tail, and most of these sites are normally phosphorylated in vivo. These KSP sites can be further divided into two separate consensus sequences, KSPXK and KSPXY (where Y is not K). The extensive phosphorylation of NF-H has been proposed to play a critical role in the determination of axonal diameter. Recent studies have shown that Cdk5, a kinase related to the cell cycle-dependent kinase Cdc2, is expressed in the brain and associates with the cytoskeleton. In vitro phosphorylation studies have shown that Cdk5 in conjunction with its activator, p35, is able to phosphorylate histone H1, dephosphorylated NF-H, as well as a synthetic peptide with the repetitive KSP motif. We have cloned the cDNAs for rat Cdk5 and p35 by reverse transcription-polymerase chain reaction and cDNA library screening and studied the phosphorylation of NF-H both in vivo and in vitro. By transient transfection assays, we have shown that NF-H can only be extensively phosphorylated in the presence of both Cdk5 and p35. This phosphorylation can be inhibited by a Cdk5-dominant negative mutant, an observation which further supports that Cdk5 is a kinase that is able to phosphorylate NF-H. By immunoprecipitating Cdk5 and p35 from the transfected cells, we have been able to show that the KSPXK repeats are the preferred phosphorylation sites for Cdk5, while the KSPXY repeats are not directly phosphorylated by Cdk5 and p35.
Population-based study on occupational risk factors for preeclampsia and gestational hypertension.

OBJECTIVES Preeclampsia is a leading cause of maternal and perinatal morbidity. Work-related factors may influence the occurrence of this disorder. This case-control study estimated the associations between work-related physical and psychosocial factors and the risk of preeclampsia and gestational hypertension. METHODS The eligible women consisted of a random sample of the women who delivered a singleton live birth in 1997-1999 in six regions of Quebec and worked during pregnancy. Cases of preeclampsia (N=102) and gestational hypertension (N=99) were compared with normotensive controls (N=4381). Information on occupational exposures at the onset of pregnancy was collected during phone interviews a few weeks after delivery. Detailed information was obtained on work schedule, postures, physical exertion, work organization, noise, vibration, and extreme temperature. Adjusted odds ratios (aOR) were estimated through polytomous logistic regression. RESULTS Women standing daily at least 1 hour consecutively without walking experienced a higher risk of preeclampsia [aOR 2.5, 95% confidence interval (95% CI) 1.4-4.6], as well as women climbing stairs frequently (aOR 2.3, 95% CI 1.2-4.1) and women working more than 5 consecutive days without a day-off (aOR 3.0, 95% CI 1.0-9.5). Squatting or kneeling, pushing or pulling objects, whole-body vibration, forced pace, job strain, and no control on breaks were positively, but nonsignificantly, associated with preeclampsia. The associations were weaker for gestational hypertension. CONCLUSIONS These findings suggest that being exposed to physically demanding and stressful occupational conditions at the onset of pregnancy increases the risk of preeclampsia.
Maximal aerobic capacity and total blood volume in highly trained middle-aged and older female endurance athletes.

The primary aim of this study was to test the hypothesis that, relative to age-matched sedentary controls, middle-aged and older female endurance athletes exhibit levels of maximal rate of O2 consumption (VO2max) similar to those previously reported in male endurance athletes in the same age group and, furthermore, that these high levels of VO2max are associated with elevated and total blood volume in 13 highly trained female runners and 17 healthy untrained women 50-70 yr of age. The runners had lower (P < 0.001) body mass index and estimated body fat relative to the controls. They also had higher levels of VO2max (2.70 +/- 0.08 vs. 1.74 +/- 0.06 l/min, 48.6 +/- 1.9 vs. 26.5 +/- 0.8 ml.kg-1.min-1, 58.0 +/- 1.8 vs. 38.8 +/- 1.2 ml.kg fat-free mass-1.min-1; all P < 0.001) and total blood volume (4,964 +/- 226 vs. 4,336 +/- 130 ml, P < 0.02; 89 +/- 4 vs. 64 +/- 2 ml/kg, P < 0.001; 106 +/- 4 vs. 96 +/- 3 ml/kg fat-free mass, P < 0.05). The elevated total blood volumes in the runners were due to both higher plasma and erythrocyte volumes. In addition, hematocrit and hemoglobin concentrations were higher in the runners (P < 0.007). VO2max was strongly (P < 0.001) related to total blood volume (r = 0.79), plasma volume (r = 0.76), and erythrocyte volume (r = 0.78) when all were expressed relative to body weight. (ABSTRACT TRUNCATED AT 250 WORDS)
Sensory acceptability and physical stability evaluation of a prebiotic soy-based dessert developed with passion fruit juice

The aim of this study was to use a factorial design approach for developing a palatable and stable soy-based dessert with the addition of Soy Protein (SP), oligofructose, and Passion Fruit Juice (PFJ). Panelists (n = 50) used a seven-point hedonic scale to assess the overall liking, degree of liking of creaminess, taste, and color of the desserts. In addition, the samples were submitted to a preference ranking test in order to evaluate the products’ preference. Water Holding Capacity (WHC) and backscattering (BS) measures were also determined to assess the physical stability of the trials. Sample F3 (35% PFJ and 2% SP) was the only one that presented a WHC index of 94.8%; moreover, none of the developed samples had synerisis after 72 hours of storage indicating adequate physical stability of the emulsion process. Samples F2 (25% PFJ, and 3.0% SP), F4 (35% PFJ, and 3.0% SP), and F5 (30% PFJ, and 2.5% SP) presented mean hedonic scores above ‘slightly liked’ for all sensory attributes. The acceptance index of samples varied from 62.50 to 88% showing the great sensory potential of such products.
Analysis of 348 consecutive cases of primary postpartum haemorrhage at a tertiary hospital in Nigeria

A retrospective analysis of 348 cases of primary postpartum haemorrhage (PPH) that occurred at the University of Ilorin Teaching Hospital, Ilorin, Nigeria between 1 January 1993 and 31 December 1996 was carried out. The incidence of PPH was 4.5%. Booking status of the patients had no relation with occurrence of PPH in this study (P > 0.05). The risk of PPH in advanced maternal age (over 35 years) and grandmultiparity (para 5 and over) was twofold higher than low maternal age (< 25 years) and low parity (para 0–1), P < 0.05, respectively. The incidence of PPH was higher in deliveries conducted by midwives than doctors (P < 0.05). Anaemic patients (PCV ⩽ 30%) were more at risk than non-anaemic patients (P < 0.05). Uterine atony, 183 (53.8%) was the most common cause of PPH and a combination of uterotonic agents and uterine massage were effective in controlling PPH in 171 (49.1%) of the cases. Seven (2.0%) patients required hysterectomy. One-third of the patients had a blood transfusion. To reduce the incidence of PPH, we recommend that doctors should supervise the delivery of parturients at risk of PPH and advocate health education against high parity.
Cellular mechanisms regulating [Ca2+]i smooth muscle.

The preceding chapters establish the primary role of Ca2+ in the activation of smooth muscle contractile proteins. In this chapter we discuss the Ca2+ transport mechanisms that determine the intracellular Ca2+ concentration ([Ca2+U and thus regulate smooth muscle contraction. Two integrated membrane systems are involved in the control of smooth muscle [Ca2+l;: (a) the plasmalemma, which is under the control of the membrane potential (Em) and agonists such as neurotransmitters hormones and autocoids, and (b) the sarcoplasmic reticulum, which is under the control of second messengers. Both membranes form a barrier to an approximately IO,OOO-foid concentration gradient; thus, an increase in permeability to Ca2+ leads to an increase in [Ca2+l;, while active ATP-fueled Ca2+ pumping and possibly Na+ -Ca2+ exchange leads to a decrease in [Ca2+l;. Plasmalemmal Ca2+ permeability is regulated by the voltage gated Ca2+ channels (VGCs) and by chemical gating of receptor operated channels (ROCs) (11, 83). In some cases, agonists also inhibit the Ca2+ extrusion pump (23). The mem­ brane potential is determined by ionic concentration gradients and per­ meabilities according to the Goldman equation and is regulated close to the K+ equilibrium potential by the opening or closing of K+ channels (11).
Preterm Labour and its Relation To Bacterial Vaginosis and Fetal Fibronectin

Preterm delivery (PTD) is the leading cause of infant morbidity and mortality. Epidemiological association between PTD and various bacteria that are part of the vaginal microflora has been reported. Bacterial vaginosis is believed to be a risk factor for preterm delivery. The aim of the present study is to investigate the association between bacterial vaginosis, cervicovaginal fetal fibronectin level and the preterm delivery of infant with low birth weight. In this study a total of 288 pregnant women were enrolled during the period between May 2008 and June 2009 at Alkoms Hospital, Libya. The present study revealed that the presence of bacterial vaginosis was related to preterm delivery of a low birth weight infants. The highest risk of preterm delivery of low birth weight infants was found among those with vaginal Gardnerella vaginalis, Mycoplasma hominis and Bacteroides spp. (6.3%), as well as women with vaginal Mycoplasma hominis, Bacteroides spp and Escherichia coli (5.9%). However Lactobacillus spp. had no effect on poor pregnancy outcome and play no role with preterm delivery of infants with low birth weight. There was also a strong relation between cervicovaginal fetal fibronectin and isolation of Mycoplasma hominis, Bacteroides spp. and Escherichia coli. In conclusion, that the effect of the abnormal vaginal flora was an independent predictor of preterm delivery. Cervicovaginal measurement of fetal fibronectin in combination with detection of bacterial vaginosis may be useful for evaluation of pregnant women with threatened premature delivery of low birth weight infants. 1 Microbiology Department Faculty of Pharmacy, Al-Mergib University, Alkomas, Libya. 2 Microbiology Department Faculty of Science, Al-Mergib University, Alkomas, Libya. 3 Faculty of Marine Resources, Al-mergib University, Zliten, Libya. Majalat Al-Ulum Al-Insaniya wat Tatbiqiya