Miracle-dz/UniFAR-FTUs huggingface dataset:
Exposure to traffic and the onset of myocardial infarction.

BACKGROUND An association between exposure to vehicular traffic in urban areas and the exacerbation of cardiovascular disease has been suggested in previous studies. This study was designed to assess whether exposure to traffic can trigger myocardial infarction. METHODS We conducted a case-crossover study in which cases of myocardial infarction were identified with the use of data from the Cooperative Health Research in the Region of Augsburg Myocardial Infarction Registry in Augsburg, in southern Germany, for the period from February 1999 to July 2001. There were 691 subjects for whom the date and time of the myocardial infarction were known who had survived for at least 24 hours after the event, completed the registry's standardized interview, and provided information on factors that may have triggered the myocardial infarction. Data on subjects' activities during the four days preceding the onset of symptoms were collected with the use of patient diaries. RESULTS An association was found between exposure to traffic and the onset of a myocardial infarction within one hour afterward (odds ratio, 2.92; 95 percent confidence interval, 2.22 to 3.83; P<0.001). The time the subjects spent in cars, on public transportation, or on motorcycles or bicycles was consistently linked with an increase in the risk of myocardial infarction. Adjusting for the level of exercise on a bicycle or for getting up in the morning changed the estimated effect of exposure to traffic only slightly (odds ratio for myocardial infarction, 2.73; 95 percent confidence interval, 2.06 to 3.61; P<0.001). The subject's use of a car was the most common source of exposure to traffic; nevertheless, there was also an association between time spent on public transportation and the onset of a myocardial infarction one hour later. CONCLUSIONS Transient exposure to traffic may increase the risk of myocardial infarction in susceptible persons.
Effect of Computed Tomography Scanning Parameters on Gold Nanoparticle and Iodine Contrast

PurposeGold nanoparticles (gold-NPs) have lately been proposed as alternative contrast agents to iodine-based contrast agents (iodine-CA) for computed tomography (CT) angiography. The aims of this study were to confirm an appropriate environment in which to evaluate such novel contrast agents, to investigate the comparative contrast of iodine-CA versus gold-NP, and to determine optimal scanning parameters for gold-NP. Materials and MethodsThree different clinical scanners were used to acquire CT images. A range of concentrations (10 mM to 1.5 M) of gold-NP and iodine-CA were scanned with varying x-ray tube voltages and currents, reconstruction kernels, protocols, and scanner models. The different environments investigated were air, water, and water with a bone simulant (Ca3(PO4)2). Regression coefficients were derived from the attenuation values plotted against concentration and compared for statistical significance using t values. ResultsAs expected, contrast was linearly related to concentrations up to 500 to 1000 mM, depending on the conditions used, whereupon a plateau of 3000 Hounsfield units was reached. Attenuation was significantly different depending on the environment used (air, water, or water and bone simulant). Contrast is dependent on the x-ray tube voltage used, with the contrast produced from iodine-CA sharply declining with increasing voltage, whereas the contrast of gold-NP varied less with tube voltage but was maximal at 120 kV in water with bone simulant. Current, reconstruction kernels, protocols, and scanner model had less effect on contrast. ConclusionWater with a bone simulant is a preferable environment for evaluating novel cardiac CT contrast agents. Relative iodine-CA versus gold-NP contrast is dependent on the scanning conditions used. Optimal scanning conditions for gold-NP will likely use an x-ray tube voltage of 120 kV.
Circulation et réseaux de migrants roumains : Une contribution à l'étude des nouvelles mobilités en Europe

La recherche, basee sur de nombreuses enquetes de terrains, analyse le phenomene de circulation migratoire apparu au depart de la Roumanie vers l'Europe occidentale a partir de la deuxieme moitie des annees 90. L'approche theorique situe l'etude dans le champ de recherche des « nouvelles migrations » et tente de clarifier, en les appliquant a la circulation roumaine, un certain nombre de concepts qui y sont associes tels la Mondialisation et le Transnationalisme. Centree sur l'apparition et le devenir des liens sociaux dans les reseaux migrants transnationaux, l'analyse porte ensuite sur les formes d'organisations sociales qui president a ces mouvements multipolaires – et souvent clandestins- en dehors de toute structure formelle. Il s'agit de montrer que les reseaux, bases sur des types de liens tres divers, vehiculent, pour leurs acteurs, des ressources particulierement utiles dans l'espace des migrations transnationales.
Hypothalamic Neurosecretory and Circadian Vasopressinergic Neuronal Systems in the Blind Cone‐Rod Homeobox Knockout Mouse (Crx−/−) and the 129sv Wild‐Type Mouse

Vasopressin (AVP) is both a neuroendocrine hormone located in magnocellular neurosecretory neurons of the hypothalamus of mammals but also a neurotransmitter/neuromodulator in the parvocellular suprachiasmatic nucleus (SCN). The SCN is the endogenous clock of the brain and exhibits a prominent circadian AVP rhythm. We have in this study of the brown 129sv mouse and the visual blind cone–rod homeobox gene knock out mouse (Crx−/−) with degeneration of the retinal rods and cones, but a preserved non‐image forming optic system, studied the temporal Avp expression in both the neurosecretory magnocellular and parvocellular vasopressinergic systems in both genotypes. We here present a detailed mapping of all classical hypothalamopituitary and accessory magnocellular nuclei and neurons in the hypothalamus by use of immunohistochemistry and in situ hybridization in both genotypes. Semiquantitative in situ hybridization revealed a very high expression of Avp mRNA in all the magnocellular nuclei compared with a much lower level in the parvocellular suprachiasmatic nucleus. In a series of mice killed every 4 hours, the Avp mRNA expression in the SCN showed a significant daily rhythm with a zenith at late day time and nadir during the dark in both the Crx−/− and the wild type mouse. None of the magnocellular neurosecretory neurons exhibited a diurnal vasopressin expression. Light stimulation of both genotypes during the dark period did not change the Avp expression in the SCN. This shows that Avp expression in the mouse SCN is independent of Crx‐regulated photoreceptor systems. J. Comp. Neurol. 521:4061–4074, 2013. © 2013 Wiley Periodicals, Inc.
BubR1 Is Required for a Sustained Mitotic Spindle Checkpoint Arrest in Human Cancer Cells Treated with Tubulin-Targeting Pyrrolo-1,5-Benzoxazepines

Intrinsic or acquired resistance to chemotherapy is a major clinical problem that has evoked the need to develop innovative approaches to predict and ultimately reverse drug resistance. A prolonged G2M arrest has been associated with apoptotic resistance to various microtubule-targeting agents (MTAs). In this study, we describe the functional significance of the mitotic spindle checkpoint proteins, BubR1 and Bub3, in maintaining a mitotic arrest after microtubule disruption by nocodazole and a novel series of MTAs, the pyrrolo-1,5-benzoxazepines (PBOXs), in human cancer cells. Cells expressing high levels of BubR1 and Bub3 (K562, MDA-MB-231, and HeLa) display a prolonged G2M arrest after exposure to MTAs. On the other hand, cells with low endogenous levels of mitotic spindle checkpoint proteins (SK-BR-3 and HL-60) transiently arrest in mitosis and undergo increased apoptosis. The phosphorylation of BubR1 correlated with PBOX-induced G2M arrest in four cell lines tested, indicating an active mitotic spindle checkpoint. Gene silencing of BubR1 by small interfering RNA interference reduced PBOX-induced G2M arrest without enhancing apoptotic efficacy. Further analysis demonstrated that PBOX-treated BubR1-depleted cells were both mononucleated and multinucleated with a polyploid DNA content, suggesting a requirement for BubR1 in cytokinesis. Taken together, these results suggest that BubR1 contributes to the mitotic checkpoint induced by the PBOXs.
Acute shifts in baroreflex control of renal sympathetic nerve activity induced by REM sleep and grooming in rats

The present study aimed to determine the impact of REM sleep and grooming on the baroreflex stimulus–response curve for renal sympathetic nerve activity (RSNA). At least 3 days before study, Wistar female rats (n= 12) were chronically implanted with catheters to measure systemic arterial pressure (Pa) and to intravenously infuse vasoactive drugs. In addition, electrodes were placed for measurements of RSNA, electroencephalogram, trapezius electromyogram and electrocardiogram. The baroreflex curve for RSNA was determined by changing Pa using rapid intravenous infusions of phenylephrine and nitroprusside and then fitted to an inverse sigmoid function curve. REM sleep induced a vertical suppression of the Pa–RSNA baroreflex curve, which was characterized by significant decreases in the maximum response (by 72.0%, P < 0.05) and the maximum gain (by 4.02% mmHg−1, P < 0.05) compared with NREM sleep level. Grooming shifted the Pa–RSNA baroreflex curve upward and to the right, which was associated with increases in the maximum response (by 45.2%, P < 0.05), the minimum response (by 20.7%, P < 0.05) and the pressure at the centring point (by 11.1 mmHg, P < 0.05). These data suggest that the Pa–RSNA baroreflex curve was shifted acutely and differently in a state‐dependent manner during natural sleep and wake cycle in rats.
Evaluation of Possible Correlations between Antifungal Susceptibilities of Filamentous Fungi In Vitro and Antifungal Treatment Outcomes in Animal Infection Models

ABSTRACT Nine isolates of filamentous fungi previously tested in 11 different laboratories for their susceptibilities to amphotericin B and itraconazole in vitro were injected intravenously into mice and guinea pigs, and responses to treatment with both agents were studied. The experiments were done in a single laboratory. Mean survival times, the percentages of animals surviving 12 days after infection, and culture results for samples of deep organs obtained postmortem were used as markers of antifungal efficacy. Because of variations in organism pathogenicity, interpretable test systems in vivo could not be established for Fusarium spp. in mice or guinea pigs or forPseudallescheria boydii in mice, even with the use of immunosuppressive pretreatments. Among the infections that could be evaluated, some degree of response to the corresponding treatment in vivo was seen in animals infected with each of two Rhizopus arrhizus isolates susceptible to amphotericin B at <0.5 μg/ml and Aspergillus spp. isolates susceptible to itraconazole at <1.0 μg/ml. Conversely, no responses were apparent with infecting strains for which MICs were ≥2 μg/ml (amphotericin B) or ≥1 μg/ml (itraconazole). However, the limitations of the intravenous challenge systems studied mean that no firm conclusion relating MICs in vitro to the lowest effective doses in vivo could be drawn.
Genetic and Functional Analysis of Full-Length Human Immunodeficiency Virus Type 1 env Genes Derived from Brain and Blood of Patients with AIDS

ABSTRACT The genetic evolution of human immunodeficiency virus type 1 (HIV-1) in the brain is distinct from that in lymphoid tissues, indicating tissue-specific compartmentalization of the virus. Few primary HIV-1 envelope glycoproteins (Envs) from uncultured brain tissues have been biologically well characterized. In this study, we analyzed 37 full-length env genes from uncultured brain biopsy and blood samples from four patients with AIDS. Phylogenetic analysis of intrapatient sequence sets showed distinct clustering of brain relative to blood env sequences. However, no brain-specific signature sequence was identified. Furthermore, there was no significant difference in the number or positions of N-linked glycosylation sites between brain and blood env sequences. The patterns of coreceptor usage were heterogeneous, with no clear distinction between brain and blood env clones. Nine Envs used CCR5 as a coreceptor, one used CXCR4, and two used both CCR5 and CXCR4 in cell-to-cell fusion assays. Eight Envs could also use CCR3, CCR8, GPR15, STRL33, Apj, and/or GPR1, but these coreceptors did not play a major role in virus entry into microglia. Recognition of epitopes by the 2F5, T30, AG10H9, F105, 17b, and C11 monoclonal antibodies varied among env clones, reflecting genetic and conformational heterogeneity. Envs from two patients contained 28 to 32 N-glycosylation sites in gp120, compared to around 25 in lab strains and well-characterized primary isolates. These results suggest that HIV-1 Envs in brain cannot be distinguished from those in blood on the basis of coreceptor usage or the number or positions of N-glycosylation sites, indicating that other properties underlie neurotropism. The study also demonstrates characteristics of primary HIV-1 Envs from uncultured tissues and implies that Env variants that are glycosylated more extensively than lab strains and well-characterized primary isolates should be considered during development of vaccines and neutralizing antibodies.
Menstrual characteristics associated with endometriosis

This case‐controlled study investigates whether the presence of menstrual characteristics, which may increase the exposure of the peritoneal cavity to retrograde menstruation, increases the risk of developing endometriosis. The menstrual characteristics considered were 1. age at menarche of less than 12 years, 2. duration of menstrual flow greater than five days and 3. menstrual cycle lengths of < 28 days. The frequency with which these menstrual characteristics occurred in 305 women with proven endometriosis was compared with their frequency in 305 age‐matched women without endometriosis. Adjusting for the confounding factors of parity, age at first childbirth and social class, the only menstrual characteristic that was significantly associated with endometriosis was menstrual cycle lengths of less than 28 days (odds ratio 1.83; 95% confidence intervals 1.60–2.55). There was insufficient evidence to conclude that the presence of menstrual characteristics which may increase the exposure of the peritoneal cavity to retrograde menstruation, increase a woman's risk of developing endometriosis. The association of short menstrual cycle lengths with endometriosis may have been consequential rather than causal.
Searching for a better assessment of the individual coronary risk profile. The role of angiotensin-converting enzyme, angiotensin II type 1 receptor and angiotensinogen gene polymorphisms.

BACKGROUND Polymorphisms within renin angiotensin system genes have been investigated as risk factors for coronary artery disease in different populations with contradicting results. The aim of this study was to investigate the genotype distribution and the allele frequencies of ACE, AT1R and AGT gene polymorphisms as coronary artery disease factors and their synergistic effects on coronary risk in an Italian population. METHODS AND RESULTDS: In this study ACE, AT1R and AGT gene polymorphisms were investigated in 205 consecutive coronary artery disease patients and in 209 controls. These polymorphisms were analysed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). The ACE D and AGT 235T allele, but not AT1R C allele, frequency was statistically significant in patients. An association between coronary artery disease and ACE DD, AT1R CC and AGT TT genotype, was found by univariate analysis (OR 2.06 P=0.0007, OR 2.49 P=0.009, OR 1.87 P=0. 019, respectively). At multivariate analysis ACE DD and AT1R CC genotype (OR 1.81 P=0.011, OR 2.61 P=0.011, respectively) remained associated with coronary heart disease. Subjects carrying the ACE DD genotype and AT1R C allele showed a stronger association with myocardial infarction (OR=4.02, P<0.0001). CONCLUSION Our report indicates the increased risk of coronary artery disease in the presence of ACE DD and AT1R CC genotypes independent of other risk factors, in Italian patients. The present study stresses the relevance of screening for genetic risk factors.
Oral warfarin affects peripheral blood leukocyte IL-6 and TNFα production in rats

Warfarin is a Vitamin K (VK) antagonist that affects Vitamin K-dependent (VKD) processes, including blood coagulation, as well as processes unrelated to hemostasis such as bone growth, calcification, and growth of some cell types. In addition, warfarin exerts influence on some non-VKD-related activities, including anti-tumor and immunomodulating activity. With respect to the latter, both immune stimulating and suppressive effects have been noted in different experimental systems. To explore the in vivo immunomodulatory potential of warfarin on one type of activity (i.e., cytokine production) in two different immune cell populations (i.e., mononuclear or polymorphonuclear cells), effects of subchronic oral warfarin intake in rats on pro-inflammatory cytokine (i.e., TNFα, IL-6) production by peripheral blood mononuclear and polymorphonuclear cells (granulocytes) was examined. Differential effects of warfarin intake on TNFα and IL-6 were noted, depending on the type of peripheral blood leukocytes and on the cytokine examined. Specifically, a lack of effect on TNFα and a priming of IL-6 production by mononuclear cells along with a decrease in TNFα and a lack of effect on IL-6 in polymorphonuclear cells were seen in warfarin-exposed hosts. The cell- and cytokine-dependent effects from subchronic oral warfarin intake on peripheral blood leukocytes demonstrated in this study could, possibly, differentially affect reactions mediated by these cells. Ultimately, the observed effects in rats might have implications for those humans who are on long-term/prolonged warfarin therapy.
Enhanced Protection Against Fatal Mycobacterial Infection in SCID Beige Mice by Reshaping Innate Immunity with IFN-γ Transgene1

Humans with immune-compromised conditions such as SCID are unable to control infection caused by normally nonpathogenic intracellular pathogens such as Mycobacterium bovis bacillus Calmette-Guérin. We found that SCID beige mice lacking both lymphocytes and NK cells had functionally normal lung macrophages and yet a selectively impaired response of type 1 cytokines IFN-γ and IL-12, but not TNF-α, during M. bovis bacillus Calmette-Guérin infection. These mice succumbed to such infection. A repeated lung gene transfer strategy was designed to reconstitute IFN-γ in the lung, which allowed investigation of whether adequate activation of innate macrophages could enhance host defense in the complete absence of lymphocytes. IFN-γ transgene-based treatment was initiated 10 days after the establishment of mycobacterial infection and led to increased levels of both IFN-γ and IL-12, but not TNF-α, in the lung. Lung macrophages were activated to express increased MHC molecules, type 1 cytokines and NO, and increased phagocytic and mycobactericidal activities. Activation of innate immunity markedly inhibited otherwise uncontrollable growth of mycobacteria and prolonged the survival of infected SCID hosts. Thus, our study proposes a cytokine transgene-based therapeutic modality to enhance host defense in immune-compromised hosts against intracellular bacterial infection, and suggests a central effector activity played by IFN-γ-activated macrophages in antimycobacterial cell-mediated immunity.
Adherence to antiretroviral treatment in patients with HIV in the UK: a study of complexity

Abstract Adherence to HIV treatment regimes is a core element to viral suppression. Yet measurement of adherence is complex. Although adherence levels are good predictors of outcome, they do not always provide full explanations of observed variations in responses. This study was set up to examine the complexity of adherence measurement and to examine rates of adherence in the presence of complex measurement. A total of 502 consecutive attenders at HIV clinics in the UK (80.5% response rate) provided detailed measurement on adherence in the preceding 7 days, setting out dose adherence, as well as measures of timing and dietary conditions. In addition, a range of psychological, demographic and relationship data were gathered to understand predictors of full and partial adherence. Although 79.1% reported dose adherence in the previous 7 days, 42.8% had not taken the dose at the correct time, and 27.2% had not taken the dose under the correct circumstances. Using a more complex composite measure of full adherence, rates reduced from 79.1% to 41.5%. Comparisons of those deemed fully adherent, partially adherent and non-adherent were carried out. Those that were fully adherent were significantly more likely to be older (F=7.8, p<0.001), UK born (F=6.8, p=0.03), code ethnicity as white (F=5.3, p=0.07), record higher quality of life (χ 2=8.7, p=0.01), lower psychological symptoms (χ 2=15.2, p=0.001) and lower global distress symptoms (χ 2=6.9, p=0.03). There were no differences according to education, behavioural and attitudinal variables (disclosure, stable relationship, STI diagnosed, number of sexual partners, unprotected sex, optimism or treatment switching). Fully adherent groups were significantly more likely to be in agreement with their doctor on treatment initiation (χ 2=6.2, p=0.045), satisfied with the amount of involvement in the decision-making process (χ 2=7.3, p=.026), their wishes were considered (χ 2=12.5, p=0.002) and had monitoring of their condition (χ 2=7.1, p=0.028). Multivariate analysis showed that variables which contributed significantly at a 5% criterion level to complex adherence were physical symptoms (OR=0.56, p=0.05), psychological symptoms (OR=2.37, p<0.001), age (OR=0.96, p=0.02), education (OR=0.54, p=0.03), having more than one sexual partner (OR=0.46, p=0.03), having risky sex (OR=4.30, p=0.002) and being optimistic about treatments (OR=0.42, p=0.01). The softer markers of adherence are not usually measured in follow up and may account for variations in treatment responses. The complexity of adherence needs to be understood and addressed to maximise treatment efficacy.
Stochastic Estimation of Human Arm Impedance Using Robots With Nonlinear Frictions: An Experimental Validation

Inspired by previous research on the promising internal model-based impedance control (IMBIC) scheme, it was implemented and experiments were undertaken to determine the stochastic estimation of human arm impedance. A 2-DOF selective compliant assembly robot arm (SCARA) robot with significant nonlinear frictions was used in the experiments in order to test the accuracy and reliability of the estimation under nonlinear frictions, with the IMBIC and with a proportional derivative (PD) control, respectively. After the stochastic estimation method with the SCARA robot and the IMBIC was validated using a spring array, the method was applied to the estimation of human arm impedance. The experimental results demonstrated that the stochastic estimation using the IMBIC yields accurate and reliable estimations even under substantial frictions: the multiple coherence functions exceeded 0.95 throughout the frequency range investigated and the estimated magnitudes and phases matched well with a second-order best-fit model. Furthermore, the best-fit model demonstrated reasonable agreement with the results of previous research. The stochastic estimation using the IMBIC has also demonstrated effectiveness in the estimation of human arm impedance using conventional robots.