Miracle-dz/UniFAR-FTUs huggingface dataset:
Ozone-induced inflammation in the lower airways of human subjects.

Although ozone (O3) has been shown to induce inflammation in the lungs of animals, very little is known about its inflammatory effects on humans. In this study, 11 healthy nonsmoking men, 18 to 35 yr of age (mean, 25.4 +/- 3.5), were exposed once to 0.4 ppm O3 and once to filtered air for 2 h with intermittent exercise. Eighteen hours later, bronchoalveolar lavage (BAL) was performed and the cells and fluid were analyzed for various indicators of inflammation. There was an 8.2-fold increase in the percentage of polymorphonuclear leukocytes (PMN) in the total cell population, and a small but significant decrease in the percentage of macrophages after exposure to O3. Immunoreactive neutrophil elastase often associated with inflammation and lung damage increased by 3.8-fold in the fluid while its activity increased 20.6-fold in the lavaged cells. A 2-fold increase in the levels of protein, albumin, and IgG suggested increased vascular permeability of the lung. Several biochemical markers that could act as chemotactic or regulatory factors in an inflammatory response were examined in the BAL fluid (BALF). The level of complement fragment C3 alpha was increased by 1.7-fold. The chemotactic leukotriene B4 was unchanged while prostaglandin E2 increased 2-fold. In contrast, three enzyme systems of phagocytes with potentially damaging effects on tissues and microbes, namely, NADPH-oxidase and the lysosomal enzymes acid phosphatase and beta-glucuronidase, were increased neither in the lavaged fluid nor cells. In addition, the amounts of fibrogenic-related molecules were assessed in BALF. (ABSTRACT TRUNCATED AT 250 WORDS)
Epidural versus general anesthesia, ambient operating room temperature, and patient age as predictors of inadvertent hypothermia.

To elucidate the multifactorial nature of perioperative changes in body temperature, the influence of several clinical variables, including anesthetic technique, ambient operating room temperature, and age, were evaluated. Perioperative oral sublingual temperatures were measured in 97 patients undergoing lower extremity vascular surgery randomized to receive either general (GA) or epidural (EA) anesthesia. Surgery and anesthesia were performed in operating rooms (OR) with a relatively warm mean ambient temperature (24.5 +/- 0.4 degrees C) (GA, n = 30; EA, n = 33) or relatively cold mean ambient temperature (21.3 +/- 0.3 degrees C) (GA, n = 21; EA, n = 13). Patients were 35-94 yr old, with a mean age of 64.5 +/- 1.1 yr. A regression analysis was performed to determine the variables that correlated with intraoperative decrease in temperature and postoperative rewarming rate. The major correlates of greater intraoperative decrease in temperature were 1) GA (P = 0.003); 2) cold ambient OR temperature (P = 0.07); and 3) advancing patient age (P = 0.03). There was significant interaction between ambient OR temperature and type of anesthesia (P = 0.03): there was a greater intraoperative decrease in temperature with GA compared to EA in a cold OR but a similar decrease with GA and EA in a warm OR. The data also suggest an interaction between type of anesthesia and patient age (P = 0.06), showing a greater decrease in temperature with GA compared to EA in the younger patients, but a similar decrease between GA and EA in older patients. (ABSTRACT TRUNCATED AT 250 WORDS)
‘Lag-effect’ politics and the politicisation of New Zealand farmers: Where to from here?

Responding to diffuse agricultural pollution is plagued by the considerable period of time it can take before ecological thresholds are breached and the impacts of actions on land become evident in water. Reflecting on the recent election campaign and the findings of research conducted in 2013 to understand farmers’ perspectives on media claims that agriculture is diminishing New Zealand’s ‘100% Pure’ brand, this paper examines the social and political dimensions of this lag-effect and argues that the politicisation of New Zealand farmers has gone too far. The paper examines the implications of lag-effect politics for farmers and the new government that has inherited an already fraught implementation phase of the National Policy Statement for Freshwater Management.
Clinico-biological features and outcome of acute promyelocytic leukemia patients with persistent polymerase chain reaction-detectable disease after AIDA front-line induction and consolidation therapy

ing to protocol requirements, the diagnosis of APL was confirmed in all patients at the genetic level by reverse transcription (RT)-PCR amplification of the PML/RARα hybrid and/or by karyotypic identification of the t(15;17) translocation. All eligible patients were treated with ATRA and idarubicin for induction followed by three polychemotherapy consolidation cycles as previously reported. The degree of any coagulopathy was evaluated according to the published criteria, and the grade of any hemorrhagic syndrome was evaluated on the basis of National Cancer Institute Common Toxicity Criteria (version 2.0). Relapse risk at the time of diagnosis was established according to the criteria described by Sanz et al. Retinoic acid syndrome (RAS) was diagnosed and graded as reported by Frankel et al. Central nervous system involvement was documented by lumbar puncture which was performed in symptomatic patients based on the presence of related symptoms (nausea, vomiting, headache). According to protocol design, bone marrow samples were collected in all cases at the end of the 3 consolidation cycle and analyzed by RT-PCR of the PML/RARα transcript in order to decide further therapy. Molecular persistence of residual disease was defined as positivity for PML/RARα detected in two successive marrow samples collected 2-4 weeks apart after the end of consolidation, using an RT-PCR assay with sensitivity of 10. Patients in molecular remission were intended to receive maintenance treatment, while further intensive therapy was recommended for patients with PCR-detectable persistent disease after consolidation. For molecular studies, cryopreserved GTC samples were sent in dry ice to two referral molecular biology laboratories (Hematology Dept., University La Sapienza of Rome and Clinica Pediatrica, University of Milan-Monza) where RT-PCR analyses were performed. The reagents and laboratory protocol used for RT-PCR of PML/RARα have been reported in detail elsewhere. The sensitivity of the RT-PCR assay was determined by amplifying serially diluted RNA mixtures of a diagnostic sample with 100% of blasts and the t(15;17)-negative myeloid cell line GF-D8. The PML/RARα transcript was still detectable in the presence of 0.1 ng total RNA, that is at a final dilution of 10. Such a detection level was repeatedly obtained in several new experiments. Differences in the distribution of variables between groups of patients were analyzed by the χ test (using Yates’ correction) or Fisher’s exact test, in the case of categorical data. In the case of continuous data, Student’s t-test was used for variables with a normal distribution; otherwise the Kruskal-Wallis test was used. Results Clinico-biological characteristics at
Fast foods, energy density and obesity: a possible mechanistic link

Fast foods are frequently linked to the epidemic of obesity, but there has been very little scientific appraisal of a possible causal role. Here we review a series of studies demonstrating that the energy density of foods is a key determinant of energy intake. These studies show that humans have a weak innate ability to recognise foods with a high energy density and to appropriately down‐regulate the bulk of food eaten in order to maintain energy balance. This induces so called ‘passive over‐consumption’. Composition data from leading fast food company websites are then used to illustrate that most fast foods have an extremely high energy density. At some typical outlets the average energy density of the entire menus is ∼1100 kJ 100 g–1. This is 65% higher than the average British diet (∼670 kJ 100 g–1) and more than twice the energy density of recommended healthy diets (∼525 kJ 100 g–1). It is 145% higher than traditional African diets (∼450 kJ 100 g–1) that probably represent the levels against which human weight regulatory mechanisms have evolved. We conclude that the high energy densities of many fast foods challenge human appetite control systems with conditions for which they were never designed. Among regular consumers they are likely to result in the accidental consumption of excess energy and hence to promote weight gain and obesity.
Conversion of Th2 memory cells into Foxp3+ regulatory T cells suppressing Th2-mediated allergic asthma

Genetic and epigenetic programming of T helper (Th) cell subsets during their polarization from naive Th cells establishes long-lived memory Th cells that stably maintain their lineage signatures. However, whether memory Th cells can be redifferentiated into another Th lineage is unclear. In this study, we show that Ag-specific memory Th cells were redifferentiated into Foxp3+ T cells by TGF-β when stimulated in the presence of all-trans retinoic acid and rapamycin. The “converted” Foxp3+ T cells that were derived from Th2 memory cells down-regulated GATA-3 and IRF4 and produced little IL-4, IL-5, and IL-13. Instead, the converted Foxp3+ T cells suppressed the proliferation and cytokine production of Th2 memory cells. More importantly, the converted Foxp3+ T cells efficiently accumulated in the airways and significantly suppressed Th2 memory cell-mediated airway hyperreactivity, eosinophilia, and allergen-specific IgE production. Our findings reveal the plasticity of Th2 memory cells and provide a strategy for adoptive immunotherapy for the treatment of allergic diseases.
Distribution of leucocyte populations, and milk composition, in milk fractions of healthy quarters in dairy cows

The goal of the study was to evaluate the composition of leucocyte populations in different milk fractions as a basis on which to judge their possible role in the immune response in different compartments of the udder. The milk of one healthy quarter of nine dairy cows (SCC/quarter [les ]125000/ml; bacteriologically negative) was removed separately and during the course of milking divided into: cisternal milk (C), alveolar milk 0–25%, 25–50%, 50–75%, 75–100% (A25; A50; A75; A100, respectively) and residual milk (R). Each fraction was analysed for the main constituents, SCC and distribution of leucocyte populations and their viability. The content of fat increased steadily during milking and reached highest values in R. Protein and lactose increased from C to A25, decreased from A25 to A100 and reached their minimum in R. Na and Cl ion levels diminished from C to A25 and thereafter increased from A50 to R. Electrical Conductivity (EC) also decreased from C to A25 but remained similar within the alveolar samples and reached a minimum in R. SCC decreased from C to a minimum in A25 and increased subsequently to a significant maximum in R. Somatic cell viability increased throughout consecutive fractions with a maximum value in R. The ratio of cell populations in the various milk fractions showed a reverse trend of macrophages (M) and polymorphonuclear neutrophils (PMN). M values were highest in C while PMN levels increased to their maximum in the R fraction. The lymphocyte (L) fraction remained similar in C, A25, A50, A75 and R but was higher in A100. Proportions of L, PMN and M were, respectively, 9·3%, 38·2%, 52·3% in C, 10·9%, 64%, 25·1% in A25–A100 and 10·2%, 64·9%, 24·8% in R. Numbers of L, PMN and M in milk showed a similar pattern for all three cell types: high levels in C decreased to a minimum at A25 and increased steadily thereafter to their maxima in R. It is concluded that, for healthy quarters, M, the predominant cell type in C, are located near the teat canal, the main entrance of pathogens. Obviously they are the first immunological barriers for invading pathogens. In contrast, PMN are the most important population in the alveolar compartment. However, each leucocyte fraction had a higher concentration in C than in early alveolar fractions, thus indicating the crucial role of immune defence in the cisternal compartment.
The effect of alcohol consumption on emergency department services use among injured patients: A cross-national emergency room study.

OBJECTIVE Although injured patients in the emergency department (ED) report more frequent use of the ED compared with the general population, and alcohol-related admissions and chronic alcohol misuse have been found to be predictive of future ED admissions, these data are based on only a few U.S. studies. The purpose of this article was to explore the association of alcohol use and ED services use among injured patients cross-nationally. METHOD Binary and multinomial logistic regression were used to analyze the association of alcohol consumption with prior ED visits among 9,743 injured patients surveyed in 37 EDs in 14 countries and reported in 23 studies from the combined Emergency Room Collaborative Alcohol Analysis Project (ERCAAP) and World Health Organization Collaborative Study of Alcohol and Injuries. RESULTS Drinking within 6 hours before injury was associated with prior ED visits during the last 12 months (odds ratio = 1.25, p < .05), with a positive dose-response relationship. Heavy drinkers and those drinkers who were alcohol-dependent were also significantly more likely to report multiple prior ED visits, reflecting an elevated burden of services use. At the ED level, stigmatization of alcohol use was the only significant contextual variable that consistently predicted cross-ED variation in the relationship between drinking and ED use, in which the association was weaker in areas where alcohol use is less accepted. CONCLUSIONS This study lends additional support to the potential effectiveness of screening for acute and chronic alcohol use among ED injured patients to reduce ED services use and associated costs.
Comparative analysis of 2D games and artwork as the motivation to learn programming

In order to motivate students to learn programming, many instructors have tried to use games, robots, narative media, artwork, and so on hoping that they would impress their students. However, there has not been any comparative study of these outcomes. In this research, two outcomes of programming, games and artwork have been studied together, and the motivation factors of them have been comparatively analyzed. Processing programming environment was used as the common programming environment for the two outcomes, and the motivation of the students was analyzed using our original questionnaire based on the ARCS (Attention, Relevance, Confidence, and Satisfaction) motivation model. The questionnaire was conducted three times: early, middle, and late in the course. The average scores for all the four factors in the ARCS model were higher for the game course than the one for the artwork course for all the three trials of the questionnaire. The average scores for the four factors for the game course decreased as the learning phase progressed.
Bioluminescence Resonance Energy Transfer Reveals Ligand-induced Conformational Changes in CXCR4 Homo- and Heterodimers*

Homo- and heterodimerization have emerged as prominent features of G-protein-coupled receptors with possible impact on the regulation of their activity. Using a sensitive bioluminescence resonance energy transfer system, we investigated the formation of CXCR4 and CCR2 chemokine receptor dimers. We found that both receptors exist as constitutive homo- and heterodimers and that ligands induce conformational changes within the pre-formed dimers without promoting receptor dimer formation or disassembly. Ligands with different intrinsic efficacies yielded distinct bioluminescence resonance energy transfer modulations, indicating the stabilization of distinct receptor conformations. We also found that peptides derived from the transmembrane domains of CXCR4 inhibited activation of this receptor by blocking the ligand-induced conformational transitions of the dimer. Taken together, our data support a model in which chemokine receptor homo- and heterodimers form spontaneously and respond to ligand binding as units that undergo conformational changes involving both protomers even when only one of the two ligand binding sites is occupied.
De‐regulation of endogenous retrotransposons in mouse mammary carcinomas of diverse etiologies

Of the several families of endogenous retrovirus‐like elements present in the mouse genome, only mouse mammary tumor virus has been analyzed for its role in mammary carcino‐genesis. Very little is known about the expression and activities of other retro‐elements in normal and malignant mammary epithelium. We have begun investigating the possible involvement of the 3 retrotransposons, intracisternal A particles (IAPs), murine‐leukemia‐virus‐related (MuLVr) elements, and VL30 sequences, in neoplastic progression of the mammary gland in BALB/c mice. The purpose of the present study was to determine which of these elements was active in primary mammary carcinomas induced by chemical, hormonal and viral agents. Each of these cancers had aberrant expression of at least one of the latter retrovirus‐like components. IAP and/or MuLVr sequences were over‐expressed 3 to 100‐fold in most of the tumors as compared with normal mammary tissue, whereas VL30 expression was markedly decreased by 5‐ to 35‐fold in almost all of the neoplasms. Our results thus demonstrate that substantial changes in the expression of one or more of these 3 families of endogenous retrotransposons are triggered during mouse mammary tumorigenesis, regardless of etiology. Direct involvement of lAPs and MuLVr elements in neoplastic progression by transposition and insertional mutagenesis in the genome of several hematopoietic cell types has already been demonstrated. Their elevated expression in many mammary carcinomas suggests that these retrotransposons may also be potential participants in some pathways of mouse mammary carcinogenesis.
Protection of total body water content and absence of hyperthermia despite 2% body mass loss (‘voluntary dehydration’) in soldiers drinking ad libitum during prolonged exercise in cool environmental conditions

The extent to which humans need to replace fluid losses during exercise remains contentious despite years of focused research. The primary objective was to evaluate ad libitum drinking on hydration status to determine whether body mass loss can be used as an accurate surrogate for changes in total body water (TBW) during exercise. Data were collected during a 14.6-km route march (wet bulb globe temperature of 14.1°C ). 18 subjects with an average age of 26±2.5 (SD) years participated. Their mean ad libitum total fluid intake was 2.1±1.4 litres during the exercise. Predicted sweat rate was 1.289±0.530 l/h. There were no significant changes (p>0.05) in TBW, urine specific gravity or urine osmolality despite an average body mass loss (p<0.05) of 1.3±0.45 kg during the march. Core temperature rose as a function of marching speed and was unrelated to the % change in body mass. This suggests that changes in mass do not accurately predict changes in TBW (r=−0.16) because either the body mass loss during exercise includes losses other than water or there is an endogenous body water source that is released during exercise not requiring replacement during exercise, or both. Ad libitum water replacement between 65% and 70% of sweat losses maintained safe levels of hydration during the experiment. The finding that TBW was protected by ad libitum drinking despite ∼2% body mass loss suggests that the concept of ‘voluntary dehydration’ may require revision.
Contribution of Salmonella typhimuriumVirulence Factors to Diarrheal Disease in Calves

ABSTRACT Limited knowledge is available about the virulence mechanisms responsible for diarrheal disease caused by Salmonella typhimurium. To assess the contribution to diarrheal disease of virulence determinants identified in models of infection, we tested a collection of S. typhimurium mutants for their ability to cause enteritis in calves. S. typhimurium strains carrying mutations in the virulence plasmid (spvR),Salmonella pathogenicity island 2 (SPI-2) (spiB), or SPI-5 (sopB) caused mortality and acute diarrhea in calves. An S. typhimurium rfaJ mutant, which is defective for lipopolysaccharide outer core biosynthesis, was of intermediate virulence. Mutations in SPI-1 (hilA andprgH) or aroA markedly reduced virulence and the severity of diarrhea. Furthermore, histopathological examination of calves infected with SPI-1 or aroA mutants revealed a marked reduction or absence of intestinal lesions. These data suggest that virulence factors, such as SPI-1, which are required during intestinal colonization are more important for pathogenicity in calves than are genes required during the systemic phase of S. typhimurium infection, including SPI-2 or the spvoperon. This is in contrast to the degree of attenuation caused by these mutations in the mouse.
Modulation of Fatty Acid Transport and Metabolism by Maternal Obesity in the Human Full-Term Placenta1

ABSTRACT Knowledge of the consequences of maternal obesity in human placental fatty acids (FA) transport and metabolism is limited. Animal studies suggest that placental uptake of maternal FA is altered by maternal overnutrition. We hypothesized that high maternal body mass index (BMI) affects human placental FA transport by modifying expression of key transporters. Full-term placentas were obtained by vaginal delivery from normal weight (BMI, 18.5–24.9 kg/m2) and obese (BMI > 30 kg/m2) women. Blood samples were collected from the mother at each trimester and from cord blood at delivery. mRNA and protein expression levels were evaluated with real-time RT-PCR and Western blotting. Lipoprotein lipase (LPL) activity was evaluated using enzyme fluorescence. In vitro linoleic acid transport was studied with isolated trophoblasts. Our results demonstrated that maternal obesity is associated with increased placental weight, decreased gestational age, decreased maternal high-density lipoprotein (HDL) levels during the first and third trimesters, increased maternal triglyceride levels during the second and third trimesters, and increased maternal T3 levels during all trimesters, and decreased maternal cholesterol (CHOL) and low-density lipoprotein (LDL) levels during the third trimester; and increased newborn CHOL, LDL, apolipoprotein B100, and T3 levels. Increases in placental CD36 mRNA and protein expression levels, decreased SLC27A4 and FABP1 mRNA and protein and FABP3 protein expression, and increased LPL activity and decreased villus cytotrophoblast linoleic acid transport were also observed. No changes were seen in expression of PPARA, PPARD, or PPARG mRNA and protein. Overall this study demonstrated that maternal obesity impacts placental FA uptake without affecting fetal growth. These changes, however, could modify the fetus metabolism and its predisposition to develop diseases later in life.
High genetic risk scores for impaired insulin secretory capacity doubles the risk for type 2 diabetes in Asians and is exacerbated by Western‐type diets

Asians have among the highest incidence of type 2 diabetes (T2DM) in the world, partly due to low β‐cell function, causing them to rapidly develop T2DM when insulin resistant. This study tested the hypothesis that genetic polymorphisms are responsible for the low β‐cell function and that dietary factors interact with the genes to exacerbate their risk of T2DM.