Miracle-dz/UniFAR-FTUs huggingface dataset:
Development, validation and use of a patient knowledge questionnaire (PKQ) for patients with early rheumatoid arthritis.

OBJECTIVES To design and validate a patient knowledge questionnaire (PKQ) to use pre- and post-education programme for a group of early rheumatoid arthritis (RA) patients. The aim was to design a tool to assess knowledge acquisition before and after an arthritis information course (AIC). METHODS The PKQ design incorporated 12 multichoice questions. Validation procedures were undertaken. Following PKQ validation 30 patients were recruited from specialist practice having met the inclusion criteria. All patients attended the arthritis information course run by the multidisciplinary team. Demographic data such as age, gender, disease duration and educational level were evaluated for possible significance. RESULTS The PKQ demonstrated test-retest stability with a Pearson's correlation coefficient of 0.965 and an intraclass single measure coefficient of 0.87. Internal consistency was demonstrated with a Cronbach's alpha of 0.62. The PKQ was sensitive to change with a statistically significant improvement following three 1-h education sessions (Mann-Whitney U-test P<0.001). No correlation was found between baseline PKQ scores and age or disease duration. However, significant correlation between educational level and pre-knowledge scores (Pearson's correlation r = 0.386, P = 0.035) was demonstrated. Change in PKQ score was not associated with age, disease duration or educational level. Patients with lower initial pre-scores obtained the most improvement post-AIC (chi(2)-test P = 0.003). CONCLUSIONS The PKQ is a reliable, valid and sensitive instrument suitable for measuring the acquisition of RA knowledge in a group of early RA patients following arthritis information courses.
Immunization does not interfere with uptake and transport by motor neurons of the binding fragment of tetanus toxin

The nontoxic binding domain of tetanus toxin (fragment C or TTC) readily undergoes retrograde axonal transport from an intramuscular injection site. This property has led to investigation of TTC as a possible vector for delivering therapeutic proteins to motor neurons. However, the vast majority of individuals in the developed world have been vaccinated with tetanus toxoid and have circulating antitetanus antibodies that cross‐react with TTC and may block the delivery of a TTC‐linked therapeutic protein. However, it is uncertain whether the immune response is capable of completely neutralizing an intramuscular depot of protein prior to its internalization by presynaptic nerve terminals, where it is inaccessible to antibody. We have evaluated uptake of rhodamine‐labeled TTC following intramuscular injection in normal animals and animals vaccinated with tetanus toxoid prior to injection of fluorescently labeled TTC. All animals demonstrated uptake of TTC, with fluorescence appropriately localized to the hypoglossal nerve and nucleus. The distribution and intensity of fluorescence within neurons and processes were indistinguishable between the two groups and were characteristic of TTC. Vaccinated animals showed levels of uptake of TTC into the brain comparable to those of immunologically naïve animals as measured by quantitative fluorimetry. All vaccinated animals had protective levels of antitetanus antibodies as measured by ELISA. Uptake of TTC by nerve terminals from an intramuscular depot is an avid and rapid process and is not blocked by vaccination associated with protection from tetanus toxin. © 2006 Wiley‐Liss, Inc.
Increased MAP Kinase Inhibition Enhances Epiblast-Specific Gene Expression in Bovine Blastocysts1

ABSTRACT Mammalian blastocysts comprise three distinct lineages, namely, trophoblast, hypoblast, and epiblast, which develop into fetal placenta, extraembryonic yolk sac, and embryo proper, respectively. Pluripotent embryonic stem cells, capable of forming all adult cell types, can only be derived from the epiblast. In mouse and rat, this process is promoted by the double inhibition (2i) of mitogen-activated protein kinase kinase (MAP2K), which antagonizes FGF signaling, and glycogen synthase kinase 3 (GSK3), which stimulates the WNT pathway. We investigated variations of the 2i treatment on lineage segregation and pluripotency-related gene expression in bovine blastocysts. In vitro-fertilized embryos were cultured either in the presence of inhibitors of GSK3 (3 μM CHIR) and MAP2K (0.4 vs. 10 μM PD0325901, designated 2i and 2i+, respectively) or in 2i/2i+ with FGFR inhibitor (0.1 μM PD173074, designated 3i [2i and PD173074] and 3i+ [2i+ and PD173074]). Compared with 2i, both 2i+ and 3i+ potentiated the improvement in blastocyst morphology. Using an automated platform for multiplexed digital mRNA profiling, we simultaneously counted transcripts of 76 candidate genes in bovine blastocysts treated with multiple kinase inhibitors. We show that 2i+ medium specifically increased FGF4 and NANOG while reducing PDGFRalpha and SOX17 levels. The shift from a hypoblast to an epiblast gene expression signature was confirmed by quantitative PCR. A wide range of functionally related genes, including candidates involved in DNA methylation, were not significantly changed. This well-defined 2i+ effect was not observed after pharmacologically inhibiting FGF receptor or related MAP kinases (p38, JNK, and ERK5). In summary, our data suggest that increased MAP2K inhibition exerts its pluripotency-promoting effects through as yet unidentified signals.
A Longitudinal Analysis on the Association Between Antibiotic Use, Intestinal Microflora, and Wheezing During the First Year of Life

Objective. To examine the association between the intestinal flora at the age of three weeks and wheezing during the first year of life in a prospective birth cohort study. Methods. The Asthma and Allergy study is a prospective birth cohort study. A total of 154 children were recruited through maternity clinics. Selection criteria were vaginal delivery at term and uncomplicated perinatal period. Questionnaires were collected with data on the parents, including demography, smoking, and asthma. Data of the child on demographic factors, respiratory symptoms, and risk factors for asthma were collected at the ages of 3 weeks and 6 and 12 months. A fecal sample was collected at 3 weeks of age. Results. The frequency of wheezing averaged on 11.8%, 18.4%, and 23.5% at the three time points. In univariate analyses, increasing total concentration of anerobic bacteria were associated with increased odds of wheezing. Furthermore, several trends were observed between wheezing and Bifidobacterium and Clostridium. A final model showed a significant association between wheezing during the first year of life and antibiotic use, total concentration of anerobic bacteria, while increasing concentrations of Clostridium were protective of wheezing. Conclusion. This study demonstrated an association between antibiotics, anerobic bacteria, and wheezing during the first year of life. The effect of antibiotics was probably due to reverse causation. Since Clostridium was protective of wheezing, other anerobic bacteria are probably responsible for the increased risk of wheezing, which remains to be demonstrated.
Association of GALNT3 gene polymorphisms with bone mineral density in Chinese postmenopausal women: the Peking Vertebral Fracture study

ObjectiveGALNT3 gene encodes the glycosyltransferase polypeptide N-acetylgalactosaminyltransferase-3 (ppGalNacT3), which initiates the O-glycosylation of fibroblast growth factor 23 (FGF23) that is important in phosphorous regulation. Inactivating mutations of the GALNT3 gene can cause familial tumoral calcinosis. The aim of present study is to investigate the association of GALNT3 polymorphisms with osteoporosis phenotypes in Chinese postmenopausal women. MethodsA community-based population of 1,353 postmenopausal women was randomly selected in Beijing. Bone mineral densities (BMDs) of the lumbar spine, femoral neck (FN), and total hip (TH) were measured by dual-energy x-ray absorptiometry. Vertebral fracture phenotypes were ascertained by vertebral x-ray reading. Osteoporotic fracture phenotypes were obtained from questionnaires. Single nucleotide polymorphisms of GALNT3 were determined by TaqMan allelic discrimination assay. Differences in BMD, serum phosphorus, or serum calcium across diverse genotypes or haplotypes were analyzed by general linear model analysis of covariance. Linear regression or logistic regression was used for association analyses of different osteoporosis phenotypes, phosphorous, or calcium. Partial correlation was used to investigate the relationship between phosphorus or calcium and BMD. ResultsWe found that polymorphisms of rs1863196, rs6710518, and rs13429321 were significantly associated with FN BMD (P values of 0.002, 0.003, and 0.002, respectively). Polymorphisms of rs1863196, rs6710518, rs4667492, rs13429321, and rs6721582 were associated with TH BMD (P values of 0.002, 0.004, 0.037, 0.005, and 0.014, respectively). Haplotype-1 additive and dominant models were found to be associated with TH BMD (P values of 0.035 and 0.024, respectively). Haplotype-2 dominant model was found to be associated with FN BMD (P = 0.003) and TH BMD (P = 0.001). ConclusionsGALNT3 may play a role in genetic susceptibility to osteoporosis among Chinese postmenopausal women. Efforts should be exerted to replicate our findings in other similar and ethnically diverse populations.
Utilization of dehydrated curry leaves in different food products

Curry leaves are a popular leaf-spice used in very small quantities for their distinct aroma due to the presence of volatile oil and their ability to improve digestion. The present study was carried out to analyze the chemical composition of dehydrated curry leaves and to prepare different products by the incorporation of these leaves. Organoleptic and nutritive values of the prepared products were analyzed. Organoleptic evaluation was carried out using the nine point hedonic scale and nutritional composition was calculated using the food composition table. On the basis of findings, it was observed that calcium, iron, �-carotene content in prepared products increased significantly as the incorporation levels increased. Thus dehydrated curry leaves can be incorporated in the preparation of different food products to improve their nutrient contents.
The Lipid A 1-Phosphatase of Helicobacter pylori Is Required for Resistance to the Antimicrobial Peptide Polymyxin

ABSTRACT Modification of the phosphate groups of lipid A with amine-containing substituents, such as phosphoethanolamine, reduces the overall net negative charge of gram-negative bacterial lipopolysaccharide, thereby lowering its affinity to cationic antimicrobial peptides. Modification of the 1 position of Helicobacter pylori lipid A is a two-step process involving the removal of the 1-phosphate group by a lipid A phosphatase, LpxEHP (Hp0021), followed by the addition of a phosphoethanolamine residue catalyzed by EptAHP (Hp0022). To demonstrate the importance of modifying the 1 position of H. pylori lipid A, we generated LpxEHP-deficient mutants in various H. pylori strains by insertion of a chloramphenicol resistance cassette into lpxEHP and examined the significance of LpxE with respect to cationic antimicrobial peptide resistance. Using both mass spectrometry analysis and an in vitro assay system, we showed that the loss of LpxEHP activity in various H. pylori strains resulted in the loss of modification of the 1 position of H. pylori lipid A, thus confirming the function of LpxEHP. Due to its unique lipid A structure, H. pylori is highly resistant to the antimicrobial peptide polymyxin (MIC > 250 μg/ml). However, disruption of lpxEHP in H. pylori results in a dramatic decrease in polymyxin resistance (MIC, 10 μg/ml). In conclusion, we have characterized the first gram-negative LpxE-deficient mutant and have shown the importance of modifying the 1 position of H. pylori lipid A for resistance to polymyxin.
Minimal Structural Rearrangement of the Cytoplasmic Pore during Activation of the 5-HT3A Receptor*

Ligand-gated ion channel receptors mediate the response of fast neurotransmitters by opening in less than a millisecond. Here, we investigated the activation mechanism of a serotonin-gated receptor (5-HT3A) by systematically introducing cysteine substitutions throughout the pore-lining M1-M2 loop and M2 transmembrane domain. We hypothesized that multiple cysteines in the narrowest region of the pore, which together can form a high affinity binding site for metal cations, would reveal changes in pore structure during gating. Using cadmium (Cd2+) as a probe, two cysteine substitutions in the cytoplasmic selectivity filter, S2′C and, to a lesser extent, G-2′C, showed high affinity inhibition with Cd2+ when applied extracellularly in the open state. Cd2+ inhibition in S2′C was attenuated if applied in the presence of an open-channel inhibitor and showed voltage-dependent recovery, indicating a direct effect of Cd2+ in the pore. When applied intracellularly, Cd2+ appeared to bind S2′C receptors in the closed state. The ability of cysteine side chains at the 2′ and –2′ positions to coordinate Cd2+ in both the native open and closed states of the channel suggests that the cytoplasmic selectivity filter of 5-HT3A receptors maintains a narrow pore during channel gating.
Consumption of Quercetin and Quercetin-Containing Apple and Cherry Extracts Affects Blood Glucose Concentration, Hepatic Metabolism, and Gene Expression Patterns in Obese C57BL/6J High Fat-Fed Mice.

BACKGROUND Intake of polyphenols and polyphenol-rich fruit extracts has been shown to reduce markers of inflammation, diabetes, and hepatic complications that result from the consumption of a high-fat (HF) diet. OBJECTIVE The objective of this study was to determine whether mice fed polyphenol-rich apple peel extract (AE), cherry extract (CE), and quercetin, a phytochemical abundant in fruits including apples and cherries, would modulate the harmful effects of adiposity on blood glucose regulation, endocrine concentrations, and hepatic metabolism in HF-fed C57BL/6J male mice. METHODS Groups of 8-wk-old mice (n = 8 each) were fed 5 diets for 10 wk, including low-fat (LF; 10% of total energy) and HF (60% of total energy) control diets and 3 HF diets containing polyphenol-rich AE, CE, and quercetin (0.2% wt:wt). Also, an in vitro study used HepG2 cells exposed to quercetin (0-100 μmol/L) to determine whether intracellular lipid accumulation could be modulated by this phytochemical. RESULTS Mice fed the HF control diet consumed 36% more energy, gained 14 g more body weight, and had ∼50% elevated blood glucose concentrations (all P < 0.05) than did LF-fed mice. Mice fed HF diets containing AE, CE, or quercetin became as obese as HF-fed mice, but had significantly lower blood glucose concentrations after food deprivation (-36%, -22%, -22%, respectively; P < 0.05). Concentrations of serum C-reactive protein were reduced 29% in quercetin-fed mice compared with HF-fed controls (P < 0.05). A qualitative evaluation of liver tissue sections suggested that fruit phytochemicals may reduce hepatic lipid accumulation. A quantitative analysis of lipid accumulation in HepG2 cells demonstrated a dose-dependent decrease in lipid content in cells treated with 0-100 μmol quercetin/L (P < 0.05). CONCLUSIONS In mice, consumption of AE, CE, or quercetin appears to modulate some of the harmful effects associated with the consumption of an obesogenic HF diet. Furthermore, in a cell culture model, quercetin was shown to reduce intracellular lipid accumulation in a dose-dependent fashion.
Primary Pancreatic Lymphoma: Diagnostic and Therapeutic Dilemma

Objectives: Non-Hodgkin lymphoma predominantly involving the pancreas is a rare tumor and accounts for less than 0.7% of all pancreatic malignancies and 1% of extranodal lymphomas. Diagnosis of primary pancreatic lymphoma can be difficult because it may mimic carcinoma. The principal aims of this review were to highlight the difficulties encountered in making a diagnosis and to identify the role of surgery. Methods: A PubMed search was conducted using the following terms: primary pancreatic lymphoma and non-Hodgkin lymphoma of the pancreas. Additional references were sourced from key articles. Results: A total of 89 reported cases of pancreatic lymphoma between 1951 and 2005 were reviewed. An accurate preoperative diagnosis of primary pancreatic lymphoma is not always possible. A complete response rate of 100% and a long-term survival rate of 94% have been reported with surgery and adjuvant chemotherapy when compared with a 5-year survival rate of less than 50% and an overall 3-year disease-free survival rate of 44% with current chemotherapy, radiotherapy, or combined methods. Conclusion: Pancreaticoduodenectomy may have a therapeutic role in association with chemotherapy.
Modulation of UDP‐glucuronosyltransferase 1A1 in primary human hepatocytes by prototypical inducers

The primary objective of this study was to evaluate the modulation of UGT1A1 expression in human hepatocytes using prototypical CYP450 inducers. A bank of 16 human livers was utilized to obtain an estimate of the range of UGT1A1 protein expression and catalytic activity. Concentration‐dependent changes in UGT1A1 response were evaluated in hepatocyte cultures after treatment with 3‐methylchloranthrene, β‐napthoflavone, rifampicin, or phenobarbital. Pharmacodynamic analyses of UGT1A1 expression were conducted and compared to those of CYP450 after treatment with inducers in 2–3 different hepatocyte preparations. Additionally, expression of UGT1A1 mRNA and protein was evaluated in human hepatocytes treated with 14 different compounds known to activate differentially the human pregnane‐X‐receptor or constitutive androstane receptor. Pharmacodynamic modeling revealed EC50 values statistically significant between UGT1A1 and CYP2B6 after treatment with PB, but not statistically distinguishable between UGT1A1 and CYP's 1A2 or 3A4 after treatment with 3‐methylchloranthrene or rifampicin, respectively. UGT1A1 was most responsive to the pregnane‐X‐receptor‐agonists rifampicin, ritonavir, and clotrimazole at the mRNA level and, to a lesser extent, the constitutive androstane receptor‐activators, phenobarbital and phenytoin. Pharmacodynamic analyses support a mechanism of coordinate regulation between UGT1A1 and a number of CYP450 enzymes by multiple nuclear receptors. © 2005 Wiley Periodicals, Inc. J Biochem Mol Toxicol 19:96–108, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20058
Characterization of intrahepatic cholangiocarcinoma of the intraductal growth‐type and its precursor lesions

A cohort of patients with intraductal growth‐type intrahepatic cholangiocarcinoma (IG‐ICC) and its precursor lesions, collectively termed intraductal papillary neoplasm of the liver (IPNL), was characterized with respect to demographics, clinical manifestations, perioperative management, long‐term survival, and molecular features associated with carcinogenesis. A total of 122 patients with IPNL types 1 through 4, 108 patients with non–IG‐ICC and 210 patients with hepatolithiasis alone were studied. Expression of CDX2, TFF1, MUC1, MUC2, MUC5AC, EGFR, and p53 was determined by using immunohistochemistry. Females predominated in those with hepatolithiasis alone and IPNL. The mean age of patients with hepatolithiasis alone was 6 to 8 years younger than that of those with IPNL. The association with hepatolithiasis in patients with IPNL types 1 and 2, IPNL types 3 and 4, and non–IG‐ICC was 100%, 79%, and 64%, respectively. Mucobilia, anemia, and elevated serum carcinoembryonic antigen levels were helpful in distinguishing IG‐ICC and its precursor lesions. The mean survival of patients with IPNL type 3, IPNL type 4, and non–IG‐ICC was 55.5 months, 36.9 months, and 15.8 months, respectively. The incidence of expression of CDX2 and TFF1 was maximal in IPNL type 3. Expression and cellular distribution of MUC2 and CDX2 were similar. MUC5AC was strongly expressed in all patients with IPNL; EGFR and p53 were rarely expressed in patients with IPNL. In conclusion, hepatolithiasis appears to be a precipitating factor in the development of IPNL. Signs of mucobilia were specific for the diagnosis of IPNL. Expression of CDX2 and MUC2 are helpful in differentiating IPNL and non–IG‐ICC. Significant differences in survival associated with the various lesions studied warrants a more aggressive surgical strategy in their management. (HEPATOLOGY 2005;42:657–664.)
The sustainability of telework: an ecological-footprinting approach

Abstract This paper demonstrates the importance of a comprehensive framework to assess how telework affects sustainability. Sustainability-policy evaluation rarely considers substitution effects despite broad recognition that overall lifestyles must be analyzed to gauge how policy-induced behavioral changes translate into net environmental impact. Casestudy data indicate that telework has far-reaching, complex, and varied effects on lifestyle practices, with potentially important environmental implications. Because adjustments occur across numerous consumption categories, the assessment of telework’s environmental dimensions must move beyond single-issue studies and single-dataset analysis. Ecological-footprint analysis, in combination with qualitative data, can suggest solutions to sustainability problems.
National Political Parties and Career Paths to the European Parliament

This paper explores how career paths leading to the European Parliament (EP) are influenced by the strategic goals of national political parties. Considering both individual career factors and the national electoral fate of political parties, it determines what conditions increase the likelihood that experienced or inexperienced politicians serve in the EP. Experienced politicians are more likely to reach the EP when they serve vote&#8208;seeking and policy&#8208;seeking parties while inexperienced politicians are more likely to enter the EP when their parties are opportunity seeking. Overall, I find the role of individual ambition is conditioned by party strategy to determine the institutional composition of the EP, contributing to a growing literature on the strategic use of European elections by national political parties. It suggests that the electoral goals of parties should be examined in order to understand the nature of democratic representation in the European Union.