Miracle-dz/UniFAR-FTUs huggingface dataset:
Free Radicals and Hearing: Cause, Consequence, and Criteria

ABSTRACT: Reactive oxygen and nitrogen species, including free radicals, are produced in the human body in both health and disease. In health, they may arise as regulatory mechanisms, intercellular signaling species, or as bacteriocidal agents. Their production is normally controlled by the antioxidant defense mechanisms that include intracellular enzymes‐for example, glutathione peroxidase and superoxide dismutase‐and low molecular‐mass compounds such as vitamin E or ascorbic acid. Although repair mechanisms exist, some steady‐state basal oxidative damage occurs in all individuals.
Influence of n-3 Polyunsaturated Fatty Acids Enriched Lipid Emulsions on Nosocomial Infections and Clinical Outcomes in Critically Ill Patients: ICU Lipids Study*

Objective:n-3 polyunsaturated fatty acids (contained in fish oil) have been shown to beneficially influence infection rate and clinical outcomes in surgical patients probably due to their immunomodulatory action. In contrast, study results of fish oil administration in critically ill patients are controversial. The aim of this study was to investigate the effects of n-3 polyunsaturated fatty acids on the prevalence of nosocomial infections and clinical outcomes in medical and surgical critically ill patients. Design:Prospective, multicenter, randomized, comparative, double-blind study. Setting:Seventeen Spanish ICUs during 4 years. Subjects:A total of 159 medical and surgical intensive care patients with Acute Physiology and Chronic Health Evaluation II score more than or equal to 13, expected to require total parenteral nutrition for at least 5 days. Interventions:Patients received total parenteral nutrition prepared either with a lipid emulsion containing 10% fish oil or a fish oil–free lipid emulsion. The prevalence of nosocomial infections was detected during 28 days of ICU stay. Patients were followed 6 months after discharge from the ICU for length of hospital stay, hospital mortality, and 6-month mortality. Measurements and Main Results:The number of patients with nosocomial infections was significantly reduced in the fish oil–receiving group (21.0% vs 37.2%, p = 0.035) and the predicted time free of infection was prolonged (21 ± 2 vs 16 ± 2 d, p = 0.03). No significant differences were detected for ICU, hospital, and 6-month mortality. Conclusions:The results show that administration of n-3 polyunsaturated fatty acids reduces the risk of nosocomial infections and increases the predicted time free of infections in critically ill medical and surgical patients. The administration of n-3 polyunsaturated fatty acids was safe and well tolerated.
Glycomic Analysis of Glycans Released from Glycoproteins Using Chemical Immobilization and Mass Spectrometry

Protein glycosylation is one of most common protein modifications and is involved in many biological activities. N‐linked and O‐linked glycosylation not only represent abundant glycan modifications, but also are structurally diverse. Mass spectrometry has emerged as a major method for glycomic analysis. However, glycan extraction from proteins and glycan modification are two critical steps in glycomic analysis of glycans using mass spectrometry. In this protocol, we describe a novel and high‐throughput method for isolation and modification of glycans from glycoproteins using a chemoenzymatic approach on solid‐phase. Proteins are first immobilized to a solid support and unconjugated molecules are washed away; glycans, while still linked to glycoproteins on the solid support, can be treated enzymatically or chemically on solid phase for glycan derivatization. Glycans are then released from the solid support for analysis by mass spectrometry. The procedures outlined are robust and useful for high‐throughput glycomic analysis from complex biological or clinical samples. Curr. Protoc. Chem. Biol. 6:191‐208 © 2014 by John Wiley & Sons, Inc.
Bone metabolism and adipokines: are there perspectives for bone diseases drug discovery?

Introduction: Over the past 20 years, the idea that white adipose tissue (WAT) is simply an energy depot organ has been radically changed. Indeed, present understanding suggests WAT to be an endocrine organ capable of producing and secreting a wide variety of proteins termed adipokines. These adipokines appear to be relevant factors involved in a number of different functions, including metabolism, immune response, inflammation and bone metabolism. Areas covered: In this review, the authors focus on the effects of several adipose tissue-derived factors in bone pathophysiology. They also consider how the modification of the adipokine network could potentially lead to promising treatment options for bone diseases. Expert opinion: There are currently substantial developments being made in the understanding of the interplay between bone metabolism and the metabolic system. These insights could potentially lead to the development of new treatment strategies and interventions with the aim of successful outcomes in many people affected by bone disorders. Specifically, future research should look into the intimate mechanisms regulating peripheral and central activity of adipokines as it has potential for novel drug discovery.
Impact of contextual cues in the expression of the memory associated with diazepam withdrawal: involvement of hippocampal PKMζin vivo, and Arc expression and LTP in vitro

Hippocampal synaptic plasticity has been related to learning and adaptive processes developed during chronic drug administration, suggesting the existence of a common neurobiological mechanism mediating drug addiction and memory. Moreover, protein kinase M zeta (PKMζ) is critical for the maintenance of hippocampal long‐term potentiation (LTP) and spatial conditioned long‐term memories. Also, a link between activity‐regulated cytoskeleton‐associated protein (Arc), PKMζ and LTP has been proposed. Our previous results demonstrated that re‐exposure to the withdrawal environment was able to evoke the memory acquired when the anxiety measured as a diazepam (DZ) withdrawal sign was experienced. In the present work we evaluated if the memory associated with DZ withdrawal could be affected by changes in the contextual cues presented during withdrawal and by intrahippocampal administration of a PKMζ inhibitor. We found that the context was relevant for the expression of withdrawal signs as changes in contextual cues prevented the expression of the anxiety‐like behavior observed during plus‐maze (PM) re‐exposure, the associated enhanced synaptic plasticity and the increase in Arc expression. Furthermore, intrahippocampal administration of PKMζ inhibitor previous to re‐exposure to the PM test also impaired expression of anxiety‐like behavior and the facilitated LTP. These results support the relevance of the hippocampal synaptic plasticity in the maintenance of the memory trace during benzodiazepines withdrawal, adding new evidences for common mechanisms between memory and drug addiction that can be intervened for treatment or prevention of this pathology.
THE EFFECT OF VALSARTAN AND CAPTOPRIL ON LIPID PARAMETERS IN PATIENTS WITH TYPE II DIABETES MELLITUS AND NEPHROPATHY

The study compared valsartan 80 mg or 160 mg o.d. with captopril 25 mg t.i. d. or placebo on plasma lipids in normotensive and treated hypertensive patients with type II diabetes and microalbuminuria. One hundred and twenty‐two adult outpatients were randomised to receive either valsartan 80 mg or 160 mg, captopril 25 mg or placebo for 360 days. Changes from baseline to endpoint in plasma lipid parameters were measured. The primary criterion for tolerability was the incidence of adverse events. All treatment groups showed minor changes in lipid parameters. Triglyceride increased by 2.7% (valsartan 160 mg) to 9.1% (placebo). Total cholesterol decreased under valsartan 80 mg, while other groups showed increases of up to 0.031 mmol/l. Decreases in total cholesterol (p=0.018), apolipoprotein B (p=0.042) and apolipoprotein A1 (p=0.025), were significant for the comparison of 80 mg valsartan and captopril. Valsartan 80 mg or 160 mg o.d. does not cause deleterious changes in the diabetic lipid profile and, unlike captopril, is not associated with dry cough.
Aging‐Related Increase to Inducible Atrial Fibrillation in the Rat Model

Aging and Atrial Fibrillation. Introduction: Aging is associated with atrial interstitial fibrosis and increased incidence of atrial fibrillation (AF). We hypothesized that aged rats are suitable for study of aging‐related AF and that partial atrial cellular uncoupling induced with heptanol in young rats mimics aging‐related AF.
Elevated tacrolimus trough levels in association with mycophenolate mofetil‐induced diarrhea: A case report

Abstract: The combination of tacrolimus (TAC) and mycophenolate mofetil (MMF) is frequently used for immunosuppression after organ transplantation (Tx), but the pharmacokinetics and interactions between the two drugs are poorly elucidated. We describe here the increase of TAC trough levels during MMF‐induced diarrhea in a 8‐yr‐old boy after kidney Tx. Early dose reduction of TAC, together with short‐term monitoring of TAC trough levels in the presence of diarrhea, is recommended.
Validating Self-Reported Measures of Productivity at Work: A Case for Their Credibility in a Heavy Manufacturing Setting

The extent to which employee responses to productivity surveys assess what they are intended to assess has become a pivotal issue for employers and providers. Much work is now being devoted to the validity and reliability of these self-reports. Such issues will likely be resolved only over the long term. In the interim, the skepticism of business decision-makers who are unfamiliar with survey techniques needs to be addressed. This article taps the widespread acceptance that administrative adverse events have gained as indicators of productivity loss to address this issue. Joint analyses of adverse event measures and productivity self-reports on employees at International Truck and Engine Corporation are conducted to test 2 types of criterion validity: 1) concurrent validity; do prior/concurrent adverse events associate with self-reports as logic and common sense dictate? and 2) predictive validity; do self-reports distinguish the risk of subsequent adverse events? Self-reports are found to perform well in both sets of tests. The results are explored in light of: 1) concerns that users have with respect to how self-reports are now being applied, and 2) ways in which self-reports serve as a cornerstone for 3 articles that follow in this issue.
Does the Widening Income Gap Between Urban and Rural Areasreally Restrain the Consumption

In this paper,it builds a total consumption model based on the average propensity of consumption,and then discusses the effect of the gap between urban and rural incomes on demand.The results of the analysis show that the impacts of widening gap between urban and rural incomes on consumer demand appear in different stages since the middle 1990s:Before 1998,the widening income gap promoted consumption;During 1999~2002 period,it acted alternately as restraint and promotion;And after 2003,the widening gap restrained the consumption.In addition,its impacts on consumer demand have gradually weakened in general,but they take a certain momentum of growth for inhibition at present.
Are CSR disclosures relevant for investors? Empirical evidence from Germany

Purpose – The purpose of this paper is to examine whether narrative corporate social responsibility (CSR) disclosures (the provision of textual information on companies’ environmental and social performance to external stakeholders) are associated with firm value in Germany. Design/methodology/approach – Based on the global reporting initiative guidelines, the paper uses content analysis to assess the value relevance of CSR disclosures of 130 German companies over four years. Findings – The results show that CSR information is value-relevant, but the value relevance of CSR information differs among CSR categories. Specifically, the disclosure of social information is positively associated with firm value yet environmental disclosures are not. Practical implications – The results confirm that management should be aware of the potential capital market effects of voluntary CSR disclosures, even though such disclosures may be directed at other stakeholders. Originality/value – Germany is an interesting setting as CSR disclosures are voluntarily, even though the institutional environment appears sensitive to CSR disclosures. Despite this, little research has focussed upon the value-relevance of CSR-disclosures in Germany. In addition, the results confirm that management should be aware of the potential capital market effects of voluntary CSR disclosures, even though they are not directed at shareholders as such.
Patterns and processes of dispersal behaviour in arvicoline rodents

A good understanding of mammalian societies requires measuring patterns and comprehending processes of dispersal in each sex. We investigated dispersal behaviour in arvicoline rodents, a subfamily of mammals widespread in northern temperate environments and characterized by a multivoltine life cycle. In arvicoline rodents, variation in life history strategies occurs along a continuum from precocial to delayed maturation that reflects seasonal and ecological fluctuations. We compared dispersal across and within species focusing on the effects of external (condition‐dependent) and internal (phenotype‐dependent) factors. Our data revealed substantial, unexplained variation between species for dispersal distances and a strong variation within species for both dispersal distance and fraction. Some methodological aspects explained variation across studies, which cautions against comparisons that do not control for them. Overall, the species under consideration display frequent short‐distance dispersal events and extremely flexible dispersal strategies, but they also have hitherto unexpected capacity to disperse long distances. Female arvicolines are predominantly philopatric relative to males, but we found no clear association between the mating system and the degree of sex bias in dispersal across species. Dispersal is a response to both various proximate and ultimate factors, including competition, inbreeding avoidance, mate searching and habitat quality. In particular, our review suggests that costs and benefits experienced during transience and settlement are prime determinants of condition dependence. Patterns of phenotype‐dependent dispersal are idiosyncratic, except for a widespread association between an exploration/activity syndrome and natal dispersal. Consequences for population dynamics and genetic structures are discussed.
Structural genomics of enzymes involved in sterol/isoprenoid biosynthesis

X-ray structures of two enzymes in the sterol/isoprenoid biosynthesis pathway have been determined in a structural genomics pilot study. Mevalonate-5-diphosphate decarboxylase (MDD) is a single-domain α/β protein that catalyzes the last of three sequential ATP-dependent reactions which convert mevalonate to isopentenyl diphosphate. Isopentenyl disphosphate isomerase (IDI) is an α/β metalloenzyme that catalyzes interconversion of isopentenyl diphosphate and dimethylallyl diphosphate, which condense in the next step toward synthesis of sterols and a host of natural products. Homology modeling of related proteins and comparisons of the MDD and IDI structures with two other experimentally determined structures have shown that MDD is a member of the GHMP superfamily of small-molecule kinases and IDI is similar to the nudix hydrolases, which act on nucleotide diphosphatecontaining substrates. Structural models were produced for 379 proteins, encompassing a substantial fraction of both protein superfamilies. All three enzymes responsible for synthesis of isopentenyl diphosphate from mevalonate (mevalonate kinase, phosphomevalonate kinase, and MDD) share the same fold, catalyze phosphorylation of chemically similar substrates (MDD decarboxylation involves phosphorylation of mevalonate diphosphate), and seem to have evolved from a common ancestor. These structures and the structural models derived from them provide a framework for interpreting biochemical function and evolutionary relationships.
Welfare Reform and Its Long-Term Consequences for America's Poor: Welfare Reform and the Level and Composition of Income

We use data from the Current Population Survey to estimate the effects of welfare reform, the business cycle, and the EITC on the level and composition of income and earnings across the distribution of single mothers with dependent children. We admit multiple sources of heterogeneity in policy responses across skill levels and business cycle conditions, and estimate models both at the mean of the income and earnings distributions as well as at several quantiles. Our results show that TANF raised disposable incomes an average of eight percent among higher skilled mothers, and raised earnings among low skilled mothers in the lower half of the distribution by as much as 20 percent, but that it also resulted in a significant equal-size loss of after-tax total income among the low-skilled. Strong local economies accommodated welfare waivers in the mid 1990s that fostered income and earnings gains among the less skilled. The EITC expansions of the 1990s boosted before-tax earnings across the earnings distribution, especially for the low skilled in the bottom half of the distribution, but also resulted in significant losses of total income for the low skilled. The earnings gains among the low skilled a decade after the implementation of TANF and expansions of the EITC have been more than offset by losses in transfer income and have left the most vulnerable single mothers either running in place or falling behind. * Address correspondence to James P. Ziliak, Department of Economics, University of Kentucky, Lexington, KY 40506-0034; Email: jziliak@uky.edu; Phone: 859–257–2776. We thank Peter Gottschalk and seminar participants at the University of Kentucky Center for Poverty Research conference Ten Years After: Evaluating the Long-Term Effects of Welfare Reform on Children, Families, Welfare, and Work and at the Upjohn Institute for helpful comments on an earlier draft.
The impact of passive and active smoking on inflammation, lipid profile and the risk of myocardial infarction

Objective To investigate the effect of passive smoking, active smoking and smoking cessation on inflammation, lipid profile and the risk of myocardial infarction (MI). Methods A total of 423 cases with a first MI and 465 population controls from the Maltese Acute Myocardial Infarction (MAMI) Study were analysed. Data were collected through an interviewer-led questionnaire, and morning fasting blood samples were obtained. ORs adjusted for the conventional risk factors of MI (aORs) were calculated as an estimate of the relative risk of MI. The influence of smoking on biochemical parameters was determined among controls. Results Current smokers had a 2.7-fold (95% CI 1.7 to 4.2) and ex-smokers a 1.6-fold (95% CI 1.0 to 2.4) increased risk of MI. Risk increased with increasing pack-years and was accompanied by an increase in high-sensitivity C reactive protein levels and an abnormal lipid profile. Smoking cessation was associated with lower triglyceride levels. Exposure to passive smoking increased the risk of MI (aOR 3.2 (95% CI 1.7 to 6.3)), with the OR being higher for individuals exposed to passive smoking in a home rather than in a public setting (aOR 2.0 (95% CI 0.7 to 5.6) vs aOR 1.2 (95% CI 0.7 to 2.0)). Passive smoke exposure was associated with higher levels of total cholesterol, triglycerides and total cholesterol:high-density lipoprotein cholesterol ratio compared with individuals not exposed to passive smoking. Conclusions Both active and passive smoking are strong risk factors for MI. This risk increased with increasing pack-years and decreased with smoking cessation. Such effects may be partly mediated through the influence of smoking on inflammation and lipid metabolism.
Neuromuscular Effects of Rocuronium During Sevoflurane, Isoflurane, and Intravenous Anesthesia

The potency and time course of action of rocuronium were studied in patients anesthetized with 66% nitrous oxide in oxygen and 1.5 minimum alveolar anesthetic concentration of sevoflurane or isoflurane, or a propofol infusion. Potency was estimated by using the single-bolus technique. Neuromuscular block was measured by stimulation of the ulnar nerve and by recording the force of contraction of the adductor pollicis muscle. The mean (95% confidence limits) of the 50% and 95% effective doses were estimated to be 142 (129-157) and 265 (233-301) [micro sign]g/kg, 165 (146-187) and 324 (265-396) [micro sign]g/kg, and 183 (163-207) and 398 (316-502) [micro sign]g/kg during sevoflurane, isoflurane, and propofol anesthesia, respectively (P < 0.05 for sevoflurane versus propofol). The mean +/- SD times to onset of maximal block after rocuronium 0.6 mg/kg were 0.96 +/- 0.16, 0.90 +/- 0.16, and 1.02 +/- 0.15 min during sevoflurane, isoflurane, and propofol anesthesia, respectively. The respective times to recovery of the first response in the train-of-four (TOF) stimulation (T1) to 25% and 90% were 45 +/- 13.1 and 83 +/- 29.3 min, 35 +/- 6.1 and 56 +/- 15.9 min, and 35 +/- 9.2 and 55 +/- 19.4 min. The times to recovery of the TOF ratio to 0.8 were 103 +/- 30.7, 69 +/- 20.4, and 62 +/- 21.1 min, and the 25%-75% recovery indices were 26 +/- 11.7, 12 +/- 5.0, and 14 +/- 6.9 min, respectively. There were no differences among groups in the times for onset of action or to recovery of T1 to 25%. However, the times for recovery of T1 to 90%, TOF ratio to 0.8, and recovery index in the sevoflurane group were all significantly longer compared with the other two groups (P < 0.05, < 0.01, and < 0.01, respectively). We conclude that the effects of rocuronium, especially duration of action, are significantly enhanced during sevoflurane compared with isoflurane and propofol anesthesia. Implications: In routine clinical use, the effects of rocuronium are enhanced by sevoflurane, in comparison with isoflurane and propofol anesthesia, and the recovery is slower. Particular attention should be paid to monitoring of neuromuscular block during sevoflurane anesthesia. (Anesth Analg 1998;87:936-40)
Real-Time Reconstruction of Sensitivity Encoded Radial Magnetic Resonance Imaging Using a Graphics Processing Unit

A barrier to the adoption of non-Cartesian parallel magnetic resonance imaging for real-time applications has been the times required for the image reconstructions. These times have exceeded the underlying acquisition time thus preventing real-time display of the acquired images. We present a reconstruction algorithm for commodity graphics hardware (GPUs) to enable real time reconstruction of sensitivity encoded radial imaging (radial SENSE). We demonstrate that a radial profile order based on the golden ratio facilitates reconstruction from an arbitrary number of profiles. This allows the temporal resolution to be adjusted on the fly. A user adaptable regularization term is also included and, particularly for highly undersampled data, used to interactively improve the reconstruction quality. Each reconstruction is fully self-contained from the profile stream, i.e., the required coil sensitivity profiles, sampling density compensation weights, regularization terms, and noise estimates are computed in real-time from the acquisition data itself. The reconstruction implementation is verified using a steady state free precession (SSFP) pulse sequence and quantitatively evaluated. Three applications are demonstrated; real-time imaging with real-time SENSE 1) or k-t SENSE 2) reconstructions, and 3) offline reconstruction with interactive adjustment of reconstruction settings.