Miracle-dz/UniFAR-FTUs huggingface dataset:
The role of particulate pollutants in pulmonary inflammation and asthma: evidence for the involvement of organic chemicals and oxidative stress

We review the literature indicating that the adverse health effects of ambient particulate matter involve the generation of oxidative stress and inflammation, as well as immunomodulating effects by particle-associated chemicals. We discuss evidence that diesel exhaust particle organic extracts induce reactive oxygen species in macrophages and bronchial epithelial cells, two key cell types targeted by particulate matter in the lung. Reactive oxygen species activate the promoters of cytokines and chemokines involved in allergic inflammation through activator protein-1 and nuclear factor- κB signaling pathways, which may explain exacerbation of allergic inflammation. Organic diesel exhaust particle chemicals also induce apoptosis and necrosis in bronchial epithelial cells via a mitochondrial pathway. This may be responsible for epithelial shedding and bronchial hyperreactivity in asthma.
Racial disparities in birth outcomes increase with maternal age: recent data from North Carolina.

BACKGROUND Racial disparities in birth outcomes persist in North Carolina and the United States. We examined patterns of birth outcomes and womens health measures in North Carolina by race and age to portray the largest disparities. We wanted to see if our data were consistent with the "weathering hypothesis," which holds that the health of African American women may begin to deteriorate in early adulthood, with negative effects on birth outcomes. METHODS We conducted a descriptive analysis of 1999-2003 North Carolina live birth and infant death records and 2001-2003 Behavioral Risk Factor Surveillance System survey data. Birth outcome measures examined were low birth weight, very low birth weight, infant mortality neonatal mortality and postneonatal mortality. Womens health measures examined were obesity self-reported health status, high blood pressure, high cholesterol, current smoking, and smoking during pregnancy. Rates for whites and African Americans were compared for each of three age groups. RESULTS Racial disparities in birth outcomes increase with increasing maternal age. African American teens often experience better birth outcomes than older African American women. Racial disparities in measures of womens health also increase with increasing age. CONCLUSIONS Health problems among older African American women of reproductive age may contribute substantially to racial disparities in birth outcomes. Improving the health of older African American women may be an effective strategy to reduce the overall racial disparities in birth outcomes.
The pharmacokinetics and hemodynamics of sildenafil citrate in male hemodialysis patients.

BACKGROUND Erectile dysfunction (ED) is highly prevalent in men with renal disease. The clearance of sildenafil citrate, a highly effective oral treatment for ED, is decreased in men with severe renal insufficiency, but the pharmacokinetic and hemodynamic profiles during maintenance hemodialysis in men with end-stage renal disease have not been studied. METHODS Fifteen men undergoing chronic outpatient maintenance hemodialysis received a single 50-mg oral dose of sildenafil on 2 occasions, once 2 hours before, and once 2 hours after hemodialysis, with randomized assignment to sequence. Blood and dialysate samples were collected, and hemodynamic measurements were made. RESULTS Hemodialysis did not significantly clear either sildenafil or its primary metabolite, UK-103,320. Administration after hemodialysis was associated with a 17% higher peak plasma concentration and earlier time to peak, which were not clinically meaningful, whereas the overall extent of absorption and the elimination half-life were not affected. The average extent of drug bound to plasma protein was approximately 96% in hemodialysis patients. Intradialytic hypotension was not observed more frequently when sildenafil was administered before hemodialysis. Systolic blood pressure tended to decrease less during hemodialysis when subjects were treated with sildenafil before dialysis. CONCLUSION The present study demonstrates that sildenafil is not cleared by hemodialysis, and the pharmacokinetic profile resembles more closely that observed in normal volunteers than that observed in patients with severe renal insufficiency. In addition, we found that sildenafil does not promote intradialytic hypotension.
Future Directions: Growth Prediction Models

Background: One strategy for optimizing growth hormone (GH) treatment is to develop mathematical models based on clinical data from the large numbers of subjects in the KIGS (Pfizer International Growth Study Database) and to compare the observed versus predicted growth responses in subjects with short stature secondary to idiopathic GH deficiency (GHD), Turner syndrome, small birth size and idiopathic causes of short stature. Mathematical Models: Variables employed in derived regression equations include those related to birth status, genetic potential, current clinical status, laboratory data and GH treatment schedule. These models can provide an accurate estimate of potential growth on GH therapy and the tools to optimize and individualize GH therapy to obtain maximum height with the least risk and the lowest cost. Current prediction models explain around 58% of GH responsiveness in subjects with GHD, 46% in subjects with Turner syndrome and 52% in those born small for gestational age. Future Considerations: The predictive value of these models could be improved by the inclusion of extended anthropometric variables and biological parameters such as insulin-like growth factor I levels. However, recent reports that common polymorphisms of theGH receptor (GHR) gene may be associated with variations in response to GH suggest that, in the future, molecular genetics may provide an additional tool for refining growth prediction models. This possibility is being explored in a pilot study examining the effects of candidate genes in a targeted KIGS population to determine whether the GHR geneor other gene variants contribute to growth response over the first year of GH treatment.
Backscattering and Statistical Information Fusion for Urban Area Mapping Using TerraSAR-X Data

With the launch of the German TerraSAR-X system, a new generation of high-resolution spaceborne SAR data is available. This opens new perspectives and challenges for the automatic interpretation of urban environments. In fact, a rich information content, previously hidden or not clearly distinguishable in low resolution images such as urban structures (small buildings, vehicles, etc), is now disclosed. However, only proper approaches are able to retrieve automatically this new detailed information. This paper provides solutions for the semi-automatic interpretation and mapping of urban areas using the high resolution provided by TerraSAR-X data. Our solutions take into the increase, with the high resolution, of the visibility of some man-made structures whose scattering response has improved with the high frequency X-band SAR sensor carried by the TerraSAR-X system. They are mainly based on two steps. Firstly, we extract and describe two kinds of information: backscattering and statistical. Secondly, we propose to use information fusion techniques where intelligence has been introduced and enhanced in the way the different information is processed or treated, so that accurate mapping of urban areas could be reached. This mapping is performed through semantic categorization and retrieval of the different scene contents. Promising improvements and real progress toward automatic urban area mapping have been achieved using TerraSAR-X data.
Immunohistochemistry of normal human knee synovium: a quantitative study

Objective: To describe the immunohistochemical characteristics of knee synovium from normal healthy subjects. Methods: 12 healthy subjects underwent needle biopsy of knee synovium. Using antibodies directed against CD3, CD4, CD8, L26, Kp-1,and HLA-DR, detailed quantitative immunohistochemical analysis of various cell subpopulations was undertaken. Results: The mean (SD) age of the subjects was 37 (9) years (five male, seven female). All had a negative history for arthritis, no knee pain, and a totally normal joint examination except for the presence of retropatellar crepitus in five. For technical reasons staining for all immunohistochemical markers could not be achieved in all subjects. CD3+ T lymphocytes were seen in nine of 10 subjects, either diffusely or, more commonly, in perivascular areas. CD4+ cells were seen in synovium in three of seven subjects and CD8+ cells in six of eight subjects, in almost equal numbers (CD4:CD8, 1.1:1). L26+ B lymphocytes were not seen in any biopsy. Kp1+ macrophages were found in 10 of 10 subjects, predominantly in surface lining cells, and in small numbers in diffuse and perivascular locations. HLA-DR+ cells were seen in 10 of 10 subjects, predominantly in surface lining cells and diffusely, but a few were seen perivascularly. Conclusions: Synovium from apparently normal subjects contained a wide range of different cell subpopulations but no B cells. The significance of these immune cells in normal synovium is unclear. A better understanding of their role in normal synovium may be important in analysing the transition to synovitis.
Crystal Structure of the HNF4α Ligand Binding Domain in Complex with Endogenous Fatty Acid Ligand*

HNF4α is an orphan member of the nuclear receptor family with prominent functions in liver, gut, kidney and pancreatic β cells. We have solved the x-ray crystal structure of the HNF4α ligand binding domain, which adopts a canonical fold. Two conformational states are present within each homodimer: an open form with α helix 12 (α12) extended and collinear with α10 and a closed form with α12 folded against the body of the domain. Although the protein was crystallized without added ligands, the ligand binding pockets of both closed and open forms contain fatty acids. The carboxylic acid headgroup of the fatty acid ion pairs with the guanidinium group of Arg226 at one end of the ligand binding pocket, while the aliphatic chain fills a long, narrow channel that is lined with hydrophobic residues. These findings suggest that fatty acids are endogenous ligands for HNF4α and establish a framework for understanding how HNF4α activity is enhanced by ligand binding and diminished by MODY1 mutations.
Are scratchcards addictive? The prevalence of pathological scratchcard gambling among adult scratchcard buyers in the Netherlands.

AIMS To determine the prevalence of regular, potential problematic and pathological scratchcard gambling (PSG) 5 years after the introduction of scratchcards in the Netherlands. DESIGN AND PARTICIPANTS A non-proportional stratified random sample of 12,222 scratchcard buyers was approached. Regular scratchcard buyers (n = 3342) were asked to fill out the South Oaks Gambling Screen (SOGS). Those with a SOGS score of 3 or more (n = 340) were interviewed with the gambling section of the DSM-IV Diagnostic Interview Schedule (DIS-T). Weighted data were used to obtain unbiased prevalence estimates. FINDINGS The estimated prevalence of regular and potential problematic scratchcard gambling were 28.4% and 2.68%, respectively. Only 0.24% met DSM-IV criteria for PSG. Of those, only 0.09% were addicted uniquely to scratchcards. The remaining 0.15% were also addicted to other games of chance. Demographic and gambling characteristics of these 'combined' PSG (young men, mainly slot-machine players) resembled characteristics of pathological gamblers in general. In contrast to these 'combined' PSG, 'unique' PSG were mainly women between 25 and 34 years who spent relatively small amounts of money on scratchcards (equivalent to one scratchcard a day). CONCLUSION Scratchcards have a very low addiction potential among adults in the Netherlands. Given the specific characteristics of the unique PSG and the relatively small amount of money they spent, the appropriateness of DSM criteria for this particular form of gambling can be questioned.
TBX3 and its splice variant TBX3 + exon 2a are functionally similar

Tbx3, a member of the conserved family of T‐box developmental transcription factors, is a transcriptional repressor required during cardiogenesis for the formation and specification of the sinoatrial node, the pacemaker of the heart. Both the TBX3 and the highly related TBX2 genes are also associated with several cancers, most likely as a consequence of their powerful anti‐senescence properties mediated via suppression p14Arf and p21CIP expression. In melanoma, the TBX2 gene is frequently amplified and inhibition of Tbx2 function leads to senescence and up‐regulation of p21CIP, a Tbx2 target gene. Tbx3 + 2a is a splice variant containing an extra 20 amino acids encoded by exon 2a inserted into the highly conserved T‐box DNA‐binding domain. We find here that Tbx3 + 2a is evolutionary conserved and that similar insertions are largely absent from the T‐box domains of other T‐box factors. Tbx3 + 2a has been reported to lack DNA‐binding ability and act as a functional antagonist of Tbx3. By contrast, we now demonstrate that both Tbx3 and Tbx3 + 2a bind the consensus T‐element, the p21CIP1 promoter, and the Nppa cardiac target gene. Both isoforms also function as repressors of p21CIP1 and Nppa promoter activity and interact with homeobox factor Nkx2‐5. When ectopically expressed in the embryonic heart of mice, Tbx3 and Tbx3 + 2a both suppressed chamber formation and repressed expression of cardiac chamber markers Nppa and Cx40. The results suggest that in the assays used, Tbx3 and Tbx3 + 2a are functionally equivalent and that like Tbx2, Tbx3 may also function as an anti‐senescence factor in melanoma.
Assembly and transport of a premessenger RNP particle

Salivary gland cells in the larvae of the dipteran Chironomus tentans offer unique possibilities to visualize the assembly and nucleocytoplasmic transport of a specific transcription product. Each nucleus harbors four giant polytene chromosomes, whose transcription sites are expanded, or puffed. On chromosome IV, there are two puffs of exceptional size, Balbiani ring (BR) 1 and BR 2. A BR gene is 35–40 kb, contains four short introns, and encodes a 1-MDa salivary polypeptide. The BR transcript is packed with proteins into a ribonucleoprotein (RNP) fibril that is folded into a compact ring-like structure. The completed RNP particle is released into the nucleoplasm and transported to the nuclear pore, where the RNP fibril is gradually unfolded and passes through the pore. On the cytoplasmic side, the exiting extended RNP fibril becomes engaged in protein synthesis and the ensuing polysome is anchored to the endoplasmic reticulum. Several of the BR particle proteins have been characterized, and their fate during the assembly and transport of the BR particle has been elucidated. The proteins studied are all added cotranscriptionally to the pre-mRNA molecule. The various proteins behave differently during RNA transport, and the flow pattern of each protein is related to the particular function of the protein. Because the cotranscriptional assembly of the pre-mRNP particle involves proteins functioning in the nucleus as well as proteins functioning in the cytoplasm, it is concluded that the fate of the mRNA molecule is determined to a considerable extent already at the gene level.
Title: The effects of organisational and financial health system interventions on quality in health care: Evidence from systematic reviews Running Title: Health system intervention effects on quality

The full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-pro t purposes provided that: • a full bibliographic reference is made to the original source • a link is made to the metadata record in DRO • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders. Please consult the full DRO policy for further details.
In vitro growth response of bread‐spoilage Bacillus strains to selected natural antimicrobials

This study assessed the in vitro responses of Bacillus (B.) strains isolated from ropey bread to natural antimicrobials under optimum growth conditions. The responses of six Bacillus strains [B. subtilis (2), B. licheniformis (2) and B. pumilus (2)] to acetic acid (AA), lactic acid (LA), calcium lactate (CL) and a lactate‐containing cocktail (LCC), singly and in combinations were determined and compared to calcium propionate (CP). Isolates were each inoculated into flasks containing Nutrient Broth (NB) and the respective antimicrobial treatments and pHs were left unadjusted. A duplicate set of flasks, also containing NB and the respective antimicrobials, but adjusted to pH's corresponding to those of baked brown bread containing the same antimicrobials was also inoculated. Growth curves were obtained spectrophotometrically and used to estimate lag times. The organic acids used in this study [0.1% (v/v) AA and 0.25% (v/v) LA] singly and in combination with each other and with CL, CP or LCC, completely inhibited the growth of all six Bacillus strains, but only at non‐adjusted pHs. The efficacies of LA, AA and CL notably decreased when the pH of the test media containing the respective preservatives was adjusted to the corresponding in situ (bread) values. However, the natural antimicrobials were still as effective as CP in retarding growth of the six Bacillus strains at the in situ (bread) pH values.
FGFR3 P250R Mutation Increases the Risk of Reoperation in Apparent ‘Nonsyndromic’ Coronal Craniosynostosis

Many patients with a clinical diagnosis of “nonsyndromic” coronal craniosynostosis have been found to be heterozygous for the fibroblast growth factor receptor 3 (FGFR3) mutation Pro250Arg. The phenotype associated with this mutation is variable and lacks highly distinctive features, so it is difficult to diagnose on clinical examination alone. The authors present a retrospective study of 76 patients with isolated coronal synostosis who were operated on in a single dedicated craniofacial unit over 25 years. The authors investigated whether any single factor, including the presence of a FGFR3 Pro250Arg mutation, predisposed to an increased transcranial reoperation rate. Eight patients had repeat transcranial surgery for a functional indication. Heterozygosity for the FGFR3 Pro250Arg mutation, present in 29 patients in the cohort, was the only factor found to have a significant association (P = 0.048) with the transcranial reoperation rate. Six patients (20.7%) with the mutation underwent reoperation on the basis of raised intracranial pressure, as compared with two patients (4.3%) without the mutation. This highlights the need for genetic analysis and long-term clinical follow-up in apparently “isolated” coronal synostosis.
Infant fussing and crying patterns in the first year in an urban community in Denmark

Infant crying amounts and patterns in 590 1‐ to 12‐month‐old infants in an urban community in Denmark were studied using the Crying Patterns Questionnaire. The impact of the crying on parents and the primary health services was also assessed. The results showed that Danish mothers leave their infants to “cry out” substantially less than mothers in the UK and North America. Despite this difference, mean crying amounts, crying patterns and the incidence of persistent crying were similar to those reported in earlier western studies. The findings support the view that the infant crying peak in the first 3 months is due to normal maturational and developmental processes.
Allogeneic stem-cell transplantation as salvage therapy for patients with diffuse large B-cell non-Hodgkin's lymphoma relapsing after an autologous stem-cell transplantation: an analysis of the European Group for Blood and Marrow Transplantation Registry.

PURPOSE To analyze the outcome, including nonrelapse mortality (NRM), relapse rate (RR), progression-free survival (PFS), and overall survival (OS), of patients with diffuse large B-cell non-Hodgkin's lymphoma (DLBCL) relapsed after an autologous stem-cell transplantation (ASCT) and treated with an allogeneic stem-cell transplantation (allo-SCT). PATIENTS AND METHODS The European Group for Blood and Marrow Transplantation database was scanned for a first allo-SCT in relapsed DLBCL after a previous ASCT between 1997 and 2006. Other inclusion criteria were age at allo-SCT ≥ 18 years and availability of an HLA-identical sibling or a matched unrelated donor. A total of 101 patients (57 males; median age, 46 years) were included. Median follow-up for survivors was 36 months. RESULTS Myeloablative conditioning regimen was used in 37 patients and reduced intensity conditioning (RIC) was used in 64 patients. Three-year NRM was 28.2% (95% CI, 20% to 39%), RR was 30.1% (95% CI, 22% to 41%), PFS was 41.7% (95% CI, 32% to 52%), and OS was 53.8% (95% CI, 44% to 64%). NRM was significantly increased in patients ≥ 45 years (P = .01) and in those with an early relapse (< 12 months) after ASCT (P = .01). RR was significantly higher in refractory patients (P = .03). A time interval to relapse after ASCT of < 12 months was associated with lower PFS (P = .03). The use of RIC regimens was followed by a trend to a lower NRM (P = .1) and a trend to a higher RR (P = .1), with no differences in PFS and OS. No differences were seen between HLA-identical siblings and matched unrelated donors. CONCLUSION Allo-SCT in relapsed DLBCL after ASCT is a promising therapeutic modality. Patients with a long remission after ASCT and with sensitive disease at allo-SCT are the best candidates for this approach.
MUC1 Protein Expression in Tumor Cells Regulates Transcription of Proinflammatory Cytokines by Forming a Complex with Nuclear Factor-κB p65 and Binding to Cytokine Promoters

Background: Human MUC1 is overexpressed and abnormally glycosylated in adenocarcinomas, correlating with inflammation and tumor growth. Results: MUC1 activates NF-κB in tumors and, in complex with NF-κB p65, migrates to the nucleus, where it promotes transcription of proinflammatory cytokines. Conclusion: MUC1 is an important mediator of tumor-induced inflammation. Significance: Targeting the MUC1-p65 complex could reduce inflammation and inhibit tumor growth. MUC1 is a transmembrane glycoprotein abnormally expressed in all stages of development of human adenocarcinomas. Overexpression and hypoglycosylation of MUC1 in cancer cells compared with normal epithelial cells are likely to alter its function and affect the behavior of cancer cells. The extracellular domain, specifically the highly O-glycosylated VNTR (variable number of tandem repeats) region, plays an important role in cell-cell communication; however, we show here that it also participates intracellularly in activation of the NF-κB pathway. Transfection of MUC1− tumor cells with cDNA encoding MUC1 with 22 tandem repeats (MUC1/22TR) or two tandem repeats (MUC1/2TR) or two isoforms that lack the VNTR region (MUC1/Z and MUC1/Y) showed that the highest expression levels of NF-κB family members correlated with the presence of VNTR and the highest number of tandem repeats. Because expression of MUC1 with VNTR on tumors was previously associated with chemotactic activity for cells of the innate immune system, we investigated the influence of MUC1 expression on the NF-κB-dependent transcriptional regulation of proinflammatory cytokines. ChIP and real-time PCR experiments revealed that MUC1/22TR up-regulated IL-6 and TNF-α expression by binding to their promoter regions in a NF-κB p65-dependent manner in both MUC1-transfected and human breast cancer cells that express endogenous MUC1. This newly detected complex of MUC1 and p65 is a novel mechanism that tumors can use to promote inflammation and cancer development.