Miracle-dz/UniFAR-FTUs huggingface dataset:
Symptoms, lung function, and β2‐adrenoceptor polymorphisms in a birth cohort followed for 10 years

As little is known about the natural history of bronchial responsiveness and the development of wheezing symptoms in early childhood, a cohort of children at risk of allergy, whose lung function and bronchial responsiveness had been measured in the neonatal period, was followed prospectively for 10 (SD, 0.8) years in order to determine the role of neonatal measurements on wheezing history and later lung function. A potential role for beta‐2 adrenoceptor (β2AR) polymorphisms in these relationships was also sought as a secondary objective. Of the original 73 children, wheezing history was available in 65 (89%), and 49 (67%) attended the laboratory for physiological measurements and genotyping of β2AR. Wheezing was categorized as occurring 1) only before the fourth birthday, 2) after the fourth birthday, or 3) never. No relation was seen between neonatal and later lung function. However, neonatal bronchial responsiveness predicted subsequent FEV1 (P = 0.03). Increased neonatal bronchial responsiveness was associated with transient wheeze <4 years but not with later wheeze. Neonatal V′maxFRC was reduced in those possessing Gln27 or Arg 16 alleles, but there was no effect of β2AR polymorphisms on FEV1 at 10 years. Wheeze after 4 years of age was typical of classical asthma, as it was strongly related to atopy and bronchial responsiveness at age 10. In conclusion, we confirmed the association of neonatal bronchial responsiveness with both early wheezing and later lung function. We also showed an influence of polymorphisms at both aa16 and aa27 on neonatal lung function. Wheezing beyond 4 years, typical of classical asthma, was unrelated to early measurements of lung function or bronchial responsiveness. Pediatr Pulmonol. 2004; 38:75–81. © 2004 Wiley‐Liss, Inc.
Toll-like receptor 2 activation by bacterial peptidoglycan–associated lipoprotein activates cardiomyocyte inflammation and contractile dysfunction

Objective:Although cardiac dysfunction plays an important role in the pathogenesis of sepsis, the mechanisms that underlie cardiac dysfunction in sepsis remain poorly understood. Bacterial peptidoglycan-associated lipoprotein (PAL), an outer-membrane protein of Gram-negative bacteria, was recently found to be released into the bloodstream in sepsis and to cause inflammation and death in mice. The present studies assessed the effects of PAL on cardiomyocyte function and its signal transduction in cardiomyocytes. Design:Randomized prospective animal study. Setting:Research laboratory. Subjects:Male C57BL/6 mice, B6;129S-Tnfrsf1atm1ImxTnfrsf1btm1Imx/ J knockout mice, Toll-like receptor 2 (TLR2) knockout mice, and myeloid differentiation factor 88 (MyD88) knockout mice. Interventions:None. Measurements and Results:Immunohistochemical staining and immunoblot analysis indicated that intravenously injected PAL bound to myocardium. Injection of PAL decreased cardiac function in vivo. Challenge with PAL altered cell shortening and Ca2+ transients in isolated mouse cardiomyocytes but not in cardiomyocytes isolated from TLR2−/− and MyD88−/− mice. Cytokine profiling arrays demonstrated that tumor necrosis factor-&agr; (TNF&agr;), granulocyte colony-stimulating factor, and interferon-&ggr; production were elevated in PAL-treated cardiomyocytes. Increased TNF&agr; production was abolished in MyD88−/− cardiomyocytes but restored by adenovirally mediated expression of MyD88. PAL did not affect cell shortening and Ca2+ cycling in cardiomyocytes obtained from mice deficient for TNF&agr; receptor (TNFR) 1 and TNFR2 (TNFR1/2−/−). Conclusion:Our data reveal that PAL uses the TLR2/MyD88 signaling cascade to induce cardiomyocyte dysfunction and inflammatory responses and that TNF&agr; is a major mediator of PAL-induced dysfunction in cardiomyocytes. These studies suggest that circulating PAL and other TLR2 agonists may contribute to cardiac dysfunction in sepsis.
A New Trend in the HIV Epidemic Among Men Who Have Sex With Men, San Francisco, 2004–2011

Background:In San Francisco, men who have sex with men (MSM) have historically comprised 90% of the HIV epidemic. It has been suggested that given the ongoing HIV transmission among this population, there is the possibility of a high-level endemic of HIV into the future. We report on the possibility of another phase in the HIV epidemic among MSM in San Francisco. Methods:Behavioral surveillance systems monitor HIV prevalence, HIV incidence, and behaviors among populations at high risk for HIV infection. Among MSM, time–location sampling is used to obtain samples for standardized behavioral surveys, HIV-antibody and incidence testing. We analyzed National HIV Behavioral Surveillance data from MSM sampled in 2004, 2008, and 2011. Results:Three hundred eighty-six, 521, and 510 MSM were enrolled in each of the waves. Only slight changes were seen in demographics over time. We detected significant declines in unrecognized HIV infection and methamphetamine use, a significant increase in HIV testing in the past 6 months, and no changes in HIV prevalence, history of gonorrhea infection, or having multiple sex partners. Among HIV-infected men, current antiretroviral treatment (ART) use seems to have risen from 2008 to 2011. Conclusions:The trends of the last 7 years point to stable HIV prevalence as rising ART coverage results in improving survival coupled with decreasing incidence as ART use achieves viral load suppression at levels more than sufficient to offset ongoing sexual risk behavior. “Treatment as prevention” may be occurring among MSM in San Francisco.
Direct comparison between endothelin-1, N-terminal proatrial natriuretic factor, and brain natriuretic peptide as prognostic markers of survival in congestive heart failure.

BACKGROUND Endothelin-1 (ET-1) and cardiac natriuretic peptide plasma concentrations have prognostic significance in congestive heart failure (CHF). However, their respective prognostic values in this setting have never been directly compared. METHODS AND RESULTS We studied the prognostic performances of ET-1, N-terminal proatrial natriuretic factor (N-proANF), and brain natriuretic peptide (BNP) to predict the long-term cardiac mortality in fully treated patients with CHF. Peripheral plasma concentrations of the 3 peptides were measured in 109 patients (left ventricular ejection fraction [LVEF] < 35%) in New York Heart Association (NYHA) functional classes II (n = 65) or III to IV (n = 44). The outcome of the patients was evaluated 3 years after the beginning of the study, and a Cox regression model was used to identify predictors of death. Plasma concentrations of the 3 peptides increased with the severity of heart failure. By univariate analysis, 6 parameters were significantly associated with death during follow-up: ET-1 level, NYHA classes III to IV, N-proANF level, BNP level, LVEF, and age (all P < .01). By multivariate analysis, only ET-1 level and, to a lesser extent, N-proANF level contributed significantly and independently to risk stratification (chi2 = 53.4 and 12.8; P < .0001 and P < .001, respectively). CONCLUSION In a group of patients in whom the vast majority were administered angiotensin-converting enzyme inhibitor therapy, plasma ET-1 and N-proANF concentrations identify better than several clinical markers a very high-risk group, fairly amenable to heart transplantation or new therapies.
Attenuation of the pressor response to laryngoscopy and tracheal intubation with intravenous verapamil

This study was undertaken in surgical patients in order to evaluate the effects of intravenous verapamil on the circulatory responses to laryngoscopy and tracheal intubation. Laryngoscopy for tracheal intubation was initiated 1 min after thiamylal 5 mg·kg‐1 and succinylcholine 1.5 mg·kg‐1 in the control group (n = 21). The verapamil group (n = 23) received intravenous verapamil 0.1 mg·kg‐1 immediately after thiamylal–succinylcholine administration. The resulting changes in mean arterial pressure (MAP) and heart rate (HR) were continuously measured. Compared with the control group, MAP increased less in response to laryngoscopy and tracheal intubation (56 ± 13% versus 25 ± 15% above baselines, P < 0.01) and returned toward baseline sooner in patients receiving verapamil. For hypertensive patients, MAP increases from baseline after intubation were 18 ± 9% in the verapamil group, and 53 ± 14% in the control group, respectively (P < 0.001). Increases in HR response to laryngoscopy for intubation were comparable in both groups. We conclude that intravenous verapamil is effective in reducing pressor responses during endotracheal intubation, especially in hypertensive patients.
Recombinant surfactant protein C-based surfactant for patients with severe direct lung injury.

RATIONALE Patients with acute lung injury have impaired function of the lung surfactant system. Prior clinical trials have shown that treatment with exogenous recombinant surfactant protein C (rSP-C)-based surfactant results in improvement in blood oxygenation and have suggested that treatment of patients with severe direct lung injury may decrease mortality. OBJECTIVES Determine the clinical benefit of administering an rSP-C-based synthetic surfactant to patients with severe direct lung injury due to pneumonia or aspiration. METHODS A prospective randomized blinded study was performed at 161 centers in 22 countries. Patients were randomly allocated to receive usual care plus up to eight doses of rSP-C surfactant administered over 96 hours (n = 419) or only usual care (n = 424). MEASUREMENTS AND MAIN RESULTS Mortality to 28 days after treatment, the requirement for mechanical ventilation, and the number of nonpulmonary organ failure-free days were not different between study groups. In contrast to prior studies, there was no improvement in oxygenation in patients receiving surfactant compared with the usual care group. Investigation of the possible reasons underlying the lack of efficacy suggested a partial inactivation of rSP-C surfactant caused by a step of the resuspension process that was introduced with this study. CONCLUSIONS In this study, rSP-C-based surfactant was of no clinical benefit to patients with severe direct lung injury. The unexpected lack of improvement in oxygenation, coupled with the results of in vitro tests, suggest that the administered suspension may have had insufficient surface activity to achieve clinical benefit.
Urinary albumin excretion in patients with systemic lupus erythematosus without renal disease

OBJECTIVES To investigate the prevalence of microalbuminuria, urinary albumin excretion (UAE) between 20-200 μg/min, in systemic lupus erythematosus (SLE) patients without clinical renal disease, and to discover if this could predict the development of renal disease. METHODS This study made six monthly measurements of UAE, creatinine clearance, serological and clinical data in 22 ambulatory women patients with SLE, without clinical renal disease, hypertension, diabetes or heart failure. The patients were followed up for a period of 18 months (four measurements). Age and sex matched healthy controls were used as a comparative group. UAE was measured by nephelometry in three timed overnight urine samples at each visit. RESULTS There were no significant differences in the creatinine clearance between the control group and the SLE patients. Creatinine clearance did not show significant changes throughout the study period. SLE patients had wide variations in the UAE rate compared with healthy controls. In five patients (5 of 22; 23%), on occasions, there was mild, transient increase in UAE reaching the level of microalbuminuria. During follow up, one patient with basal (4.67 μg/min) and six month (4.73 μg/min) normal UAE rate, was admitted with a nephrotic syndrome confirmed on biopsy examination to be proliferative lupus nephritis. Six months after beginning treatment with prednisone and cyclophosphamide her UAE rate returned to normal values (4.65 μg/min). CONCLUSION SLE patients without clinical renal disease may have microalbuminuria, although this does not seem to warrant any specific action.
Axonal Rejoining Inhibits Injury-Induced Long-Term Changes inAplysia Sensory Neurons In Vitro

Injury of Aplysia sensory neurons, both in the CNS and in dissociated cell culture, produces long-term changes in these cells, among which are hyperexcitability and enhanced neuritic outgrowth (hypermorphogenesis). These long-term, injury-induced changes are attributable, in part, to the generation of new intrinsic cellular signals. Little is known, however, about the signals that maintain homeostasis within sensory neurons. To elucidate the role of homeostatic signals in Aplysia sensory neurons, we investigated how axonal rejoining alters the cellular consequences of axotomy. Sensory neurons in dissociated cell culture were axotomized. In some cases, the distal segment of the severed axon was then removed; in other cases, the proximal and distal segments of the severed axon were permitted to rejoin. If the severed distal segment was left unmolested, then axonal rejoining invariably occurred within 7 hr. Surprisingly, we found that the characteristic long-term cellular consequences of axotomy were suppressed by axonal rejoining. The long-term axotomy-induced changes were not inhibited merely by contact between the severed axon and another, uninjured sensory neuron. These results indicate that long-term changes in sensory neurons induced by injury are attributable, in part, to prolonged disruption of a retrograde homeostatic signal that originates in the distal segment of the growing neurite and chronically suppresses hyperexcitability and hypermorphogenesis.
The Role of Socioeconomic Status in SAT-Grade Relationships and in College Admissions Decisions

This article examines the role of socioeconomic status (SES) in the relationships among college admissions-test scores, secondary school grades, and subsequent academic performance. Scores on the SAT (a test widely used in the admissions process in the United States), secondary school grades, college grades, and SES measures from 143,606 students at 110 colleges and universities were examined, and results of these analyses were compared with results obtained using a 41-school data set including scores from the prior version of the SAT and using University of California data from prior research on the role of SES. In all the data sets, the SAT showed incremental validity over secondary school grades in predicting subsequent academic performance, and this incremental relationship was not substantially affected by controlling for SES. The SES of enrolled students was very similar to that of specific schools’ applicant pools, which suggests that the barrier to college for low-SES students in the United States is a lower rate of entering the college admissions process, rather than exclusion on the part of colleges.
Properdin, a positive regulator of complement activation, is released from secondary granules of stimulated peripheral blood neutrophils.

Properdin is an important regulatory constituent of the complement system. In contrast to most other components of complement, biosynthesis of properdin is restricted to a few cell types only, i.e., monocytes/macrophages and peripheral blood T cells. This report demonstrates the presence of properdin mRNA in peripheral blood granulocytes and shows that properdin is stored in the granules of human neutrophils and secreted upon stimulation with TNF-alpha, C5a, IL-8, or FMLP. Subcellular fractionation using Percoll density gradients and Western blot analyses revealed that the bulk of properdin is contained in the secondary granules. Moreover, flow cytometric analyses indicated that properdin is present on the surface of neutrophils. In contrast to alternative pathway components, components of the classical pathway of complement activation, such as C2 and C4, were not detected. Our findings suggest that neutrophils can actively stabilize and amplify the alternative activation pathway of complement by secretion of properdin as part of the innate defense against microorganisms.
Size‐dependent disposition of nanoparticles and microparticles following subconjunctival administration

The purpose of this study was to determine the retention and ocular distribution of subconjunctivally administered nanoparticles and microparticles. Fluorescent polystyrene particles (carboxylate modified, negatively charged) of various sizes (20 nm, 200 nm and 2 μm; Fluospheres, dose 400 μg) were administered to male Sprague‐Dawley rats by subconjunctival injection under anaesthesia. The disposition of the particles in the periocular and ocular tissues was studied for up to 60 days by quantifying the particle amounts using liquid extraction followed by spectrofluorimetric analysis. The effect of dose on the particle disposition was investigated with a 40‐μg dose of the particles. The effect of an increase in surface hydrophobicity was evaluated for the 20 and 200 nm particles at 1 day post administration. Following periocular administration, penetration into the ocular tissues was negligible for the carboxylate‐modified microparticles as well as nanoparticles. Almost the entire dose of the 200 nm and 2 μm particles was retained in the periocular tissue at 60 days post‐administration. The 20 nm particles disappeared rapidly from the periocular tissue with 15 and 8% of administered dose remaining after 1 and 7 days, respectively. The 20 nm particles could not be detected in the periocular tissue at 60‐days post‐administration. An increase in the surface hydrophobicity did not affect the periocular retention of 200 nm particles but elevated that of the 20 nm particles, at the end of day 1. It was concluded that subconjunctivally administered 200 nm and larger particles can be almost completely retained at the site of administration for at least two months. Periocular administration of particulate systems of this size would likely be useful as sustained drug delivery systems.
α-Synuclein Phosphorylation Enhances Eosinophilic Cytoplasmic Inclusion Formation in SH-SY5Y Cells

Parkinson's disease (PD) is a neurodegenerative disorder characterized by selective loss of dopaminergic neurons and the presence of Lewy bodies. Previous reports have shown that α-synuclein deposited in brain tissue from individuals with synucleinopathy is extensively phosphorylated at Ser-129. Here, we investigate the role of phosphorylation of α-synuclein in the formation of inclusions involving synphilin-1 and parkin using site-directed mutagenesis to change Ser-129 of α-synuclein to alanine (S129A) to abolish phosphorylation at this site. Coexpression of wild-type α-synuclein and synphilin-1 in human neuroblastoma SH-SY5Y cells yielded cytoplasmic eosinophilic inclusions with some features resembling Lewy bodies, whereas coexpression of S129A α-synuclein and synphlin-1 formed few or no inclusions. Moreover, coexpression of parkin with α-synuclein and synphilin-1 formed more ubiquitinated inclusions, but these inclusions decreased with expression of S129A α-synuclein instead of wild-type α-synuclein. Coimmunoprecipitation assays revealed a decreased interaction of S129A α-synuclein with synphilin-1 compared with wild-type α-synuclein. Expression of S129A α-synuclein instead of wild-type α-synuclein also decreased the association of synphilin-1 and parkin and subsequently reduced the parkin-mediated ubiquitination of synphilin-1 and the formation of ubiquitinated inclusions. Treatment of SH-SY5Y cells with H2O2 increased α-synuclein phosphorylation and enhanced the formation of inclusions formed by coexpression of α-synuclein, synphilin-1, and parkin, whereas treatment with the casein kinase 2 inhibitor 5,6-dichloro-1-β-d-ribofuranosylbenzimidazole had the opposite affect. These results indicate that phosphorylation of α-synuclein at S129 may be important for the formation of inclusions in PD and related α synucleinopathies.
Urban shrinkage and resurgence in Germany

This article questions the strict parallelism of demographic and economic development in characterising urban shrinkage in Germany. As the cases of several Ruhr cities and East German cities prove, urban economic growth can be achieved thanks to the substantial presence of modern industries and business services, and despite declines in population size. Serious shrinkages of Halle, Cottbus and Schwerin are primarily due to failures in the post-industrial transformation process. Recent policy measures strongly oriented towards slowing the downsizing process of population (via e.g. urban regeneration strategies) do not appear to be sufficient for achieving urban resurgence in these cities. More active industrial policy measures are required there to create a competitive high-tech manufacturing sector, to stimulate innovation activities and to boost its growth interdependence with modern local services and R&D infrastructure.
Differential Senescence of Maize Hybrids following Ear Removal : I. Whole Plant.

Visual senescence symptoms and associated changes in constituent contents of three field-grown maize (Zea mays L.) hybrids (Pioneer brand 3382, B73 x Mo17, and Farm Service brand 854) were compared in response to ear removal. Whole plants were harvested at eight intervals during the grain-filling period, and analyzed for dry matter, total N and nitrate N, phosphorus, sugars, and starch.Upper leaves of earless P3382 and B73 x Mo17 showed reddish discoloration by 25 days after anthesis (DAA) and all leaves had lost most of their chlorophyll by 40 DAA. In striking contrast, leaves of earless FS854 plants remained green and similar in appearance to eared controls throughout the grain-filling period.For all hybrids, ear removal led to a decrease in dry weight, reduced N, total N, and phosphorus contents of the total plant, and an increase in carbohydrate content of the leaves and stalks, relative to respective controls. Although changes in carbohydrate and N contents, which previously had been associated with senescence, were observed for all earless hybrids, these changes were followed by accelerated senescence and early death only for P3382 and B73 x Mo17. By 30 DAA, earless P3382 and B73 x Mo17 plants ceased to accumulate dry weight, total N, and phosphorus, indicating a termination of major metabolic activities. In contrast, earless FS854 plants retained a portion of these metabolic activities until 58 DAA, indicating a role for roots in determining rate of senescence development. Thus, the course of senescence was more accurately reflected by measurements of metabolic activities than by measurements of metabolite contents at any given time. These results show that the ear per se does not dictate the rate or completion of the senescence process, and implicated an association between the continued accumulation of N and associated root activities with the delayed senescence pattern of the earless FS854 plants. It is evident that studies involving control of senescence among species must also consider genotypic influences within species.