Miracle-dz/UniFAR-FTUs huggingface dataset:
Determinants of Plasminogen Activator Inhibitor 1 Activity in Treated NIDDM and Its Relation to a Polymorphism in the Plasminogen Activator Inhibitor 1 Gene

Plasminogen activator inhibitor 1 (PAI-1) activity is increased in patients with non-insulin-dependent diabetes mellitus (NIDDM) and may contribute to their excess risk of cardiovascular disease. We examined the determinants of PAI-1 activity in 146 NIDDM subjects by using specific assays of insulin and intact and des-31,32-proinsulin and measures of insulin resistance, relating these measurements to serum lipids, hypoglycemic therapy, and a common 4G/5G polymorphism in the promoter region of the PAI-1 gene. Subjects were treated with insulin, sulfonylurea, sulfonylurea plus metformin, metformin, and diet alone. In the whole group, PAI-1 activity correlated significantly with serum triglycerides (r = 0.39, P < 0.001), specific insulin (r = 0.29, P < 0.001), intact proinsulin (r = 0.24, P = 0.004), and des-31,32-proinsulin (r = 0.30, P < 0.001) and in subjects not on insulin (n = 110), with insulin sensitivity (r = −0.42, P < 0.001). There was a significant difference in PAI-1 activity among the three genotypic groups (P = 0.016); subjects with the genotype 4G/4G had PAI-1 levels one-third higher than those with the 5G/5G genotype. In the 4G/4G group, PAI-1 activity correlated significantly with triglyceride levels (r = 0.65, P < 0.0001). There was no significant difference in PAI-1 activity in the different treatment groups despite a significant difference in concentrations of intact and des-31,32-proinsulin. In a multiple regression model, insulin sensitivity and the interaction between PAI-1 4G/5G genotype and triglyceride were the strongest determinants of PAI-1 activity.In conclusion, in this sample of NIDDM subjects, the influence of triglyceride on PAI-1 seems to be genotype dependent, and this interaction is a major determinant of PAI-1 activity.
Is there a relationship between increased aortic stiffness and segmental left ventricular deformation in elite athletes? (Insights from the MAGYAR-Sport Study).

Introduction Myocardial contractility of the left ventricle (LV) is related to arterial distensibility. Sport activity is frequently associated with changes in both LV and arterial functions. This study aimed to find correlations between three-dimensional speckle-tracking echocardiography-derived segmental LV deformation parameters and echocardiographically assessed aortic stiffness index (ASI) in athletes. This study comprised 26 young elite athletes (mean age: 26.7 ± 8.4 years, nine men). Results Among segmental circumferential strains (CSs), only that of apical anterior (r = 0.40, p = 0.05), septal (r = 0.47, p = 0.01), inferior (r = 0.59, p = 0.001), lateral (r = 0.44, p < 0.05), and midventricular anteroseptal (r = 0.44, p < 0.05) segments correlated with ASI, whereas LV-CS of the midventricular anterior segment showed a correlation tendency. Only longitudinal strain of basal anteroseptal (r = -0.46, p < 0.05) and inferoseptal (r = -0.57, p < 0.01) segments showed correlations with ASI, whereas that of the basal anterior segment had only a tendency to correlate. Some segmental multidirectional strains also correlated with ASI. Conclusions Correlations could be demonstrated between increased aortic stiffness and circular function of the apical and midventricular LV fibers and longitudinal motion of the basal septum and LV anterior wall (part of LV outflow tract) in maintaining circulation in the elite athletes.
Effect of Ethanol/Trisodium Citrate Lock on Microorganisms Causing Hemodialysis Catheter-Related Infections

Purpose This in vitro study tested the effectiveness of a novel 30% ethanol/4% trisodium citrate (TSC) lock solution against the most common pathogens causing hemodialysis catheter-related infections. Methods Clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) (n=4), methicillin-sensitive S. aureus (MSSA) (n=8), methicillin-resistant Staphylococcus epidermidis (MRSE) (n=8), Pseudomonas aeruginosa (n=4) and Escherichia coli (n=4) were tested in duplicate. Bacterial suspensions of each isolate were made in a control solution of normal saline and Mueller-Hinton broth (MHB), and in a lock solution of ethanol 30%, TSC 4% and MHB. Suspensions were incubated at 37 °C for 48 h. Colony counts were determined from samples collected at t=0 h (before exposure to the ethanol/TSC lock), t=1 h (one hour after exposure to the ethanol/TSC lock), t=24 h and t=48 h. To confirm the absence of viable organisms in the lock solution, the remaining volume at 48 h was filtered through a 0.45 μm filter. The filter was rinsed with 15 mL sterile water and plated on tryptic soy agar (TSA). Results All controls demonstrated significant growth over 48 h. In the lock solutions, initial inocula were reduced to 0 viable colonies by t=1 h (6-log kill), and there was no growth at t=24 and 48 h. Filtering of lock solutions also showed no growth. These results were consistent among duplicates of all isolates. Conclusions The 30% ethanol/4% TSC lock solution consistently eradicated MRSA, MSSA, MRSE, P. aeruginosa and E. coli within 1 h of exposure. Experiments are currently underway to test this novel lock solution on preventing biofilm production by these pathogens.
Metabolic influences on neuroendocrine regulation of reproduction

Purpose of review Reproduction is a tightly regulated function in which many mechanisms contribute to ensure the survival of the species. Among those, due to the elevated energy requirements of reproduction, metabolic factors exert a pivotal role in the control of hypothalamic-pituitary-gonadal axis. Although this control may occur at multiple levels of the axis, the majority of interactions between metabolic and reproductive systems take place in the hypothalamus. In this article, we present an overview of the state-of-the-art knowledge regarding the metabolic regulation of reproduction at the central level. We aim to identify the neuroanatomical location where both functions interconnect by discussing the likelihood of each component of the neuronal hierarchical network controlling gonadotropin-releasing hormone (GnRH) release to be first-order responders to metabolic cues, especially the peripheral metabolic signals leptin, insulin, and ghrelin. Recent findings Latest evidence suggests that the primary action of leptin, insulin, and ghrelin to regulate reproduction is located upstream of the main central elicitors of gonadotropin release, Kiss1 and GnRH neurons, and neuroanatomically separated from their metabolic action. Summary The study of the neuronal interactions between the mechanisms governing metabolism and reproduction offers the platform to overcome or treat a number of prevailing metabolic and/or reproductive conditions.
Migratory birds and West Nile virus

West Nile virus was first recorded in the New World during August 1999 in New York City. Aetiology of the disease in the Old World indicated birds as the likely introductory and amplifying hosts with ornithophilous mosquitoes, e.g. Culex pipiens, as the principal vectors. Speculation regarding likely agents for movement of the virus in its new environment focused on migratory birds, but evidence to date is equivocal. While spread of the disease has been fairly rapid, at a rate of roughly 70 km a month, it has not shown the kind of long-distance, leap frog movements one might expect if transient birds were the principal introductory hosts. Furthermore, movement of the disease has not been focused southward, but shows a radiating pattern with detection sites located in all directions from New York where terrestrial habitat was available. In addition, tests among potential New World, avian hosts have revealed prolonged viraemia (up to 5 days) only in the relatively non-migratory House Sparrow (Passer domesticus). Dispersal movements by this species could account for the observed pattern of West Nile virus spread in the Western Hemisphere to date. Regardless of whether avian migration, dispersal, or some other agent is responsible, West Nile virus should reach the New World tropics in another 1-2 years, at which time a vast number of new potential introductory and amplifying avian hosts would be exposed to the disease and mosquito vectors would be available throughout most of the year, likely causing serious, long-term threats to human health and vulnerable avian populations in the region.
VEGFR1 and PKC&agr; signaling control melanoma vasculogenic mimicry in a VEGFR2 kinase-independent manner

We have recently shown that vascular endothelial growth factor-A (VEGFA), a major regulator of tumor vascularization, is essential for the organization of tumor cells into capillary-like structure (CLS), which is a hallmark of tumor vasculogenic mimicry (VM). Herein we further dissect the involvement of VEGFA and its downstream transducers, VEGF receptor 1 (VEGFR1), VEGFR2, and protein kinase C (PKC) in melanoma VM. The knockdown of VEGFR1 in three melanoma cell lines completely disrupts Matrigel-induced CLS formation, whereas inhibition of VEGFR2 kinase with a specific inhibitor, protein tyrosine kinase inhibitor II (PTKi-II), does not affect the process, indicating that VEGFR2 signaling is not involved in VEGFA-mediated melanoma VM. Furthermore, among tested PKC isoforms, only PKC&agr; and &dgr; are expressed in the melanoma cells during CLS formation. Pretreatment with selective PKC&agr; and &dgr; inhibitors blocked CLS formation. However, inhibition of PKC&agr;, but not PKC&dgr;, completely destroyed the previously formed CLS. Moreover, knockdown of PKC&agr;, but not PKC&dgr;, using small interfering RNAs abrogated CLS formation, suggesting that PKC&agr; is the major contributory factor in melanoma VM. In-vivo experiments indicate that disruption of PKC&agr; signaling significantly reduces the signs of VM in allografted B16/F10 melanoma. These findings may contribute to the development of new therapeutic agents that target melanoma VM.
Olanzapine as Alternative Therapy for Patients With Haloperidol-Induced Extrapyramidal Symptoms: Results of a Multicenter, Collaborative Trial in Latin America

Conventional antipsychotic agents can induce extrapyramidal symptoms (EPS) that may be alleviated by switching patients to novel agents such as olanzapine. Patients with schizophrenia and related disorders (ICD-10) who were taking haloperidol (N = 94; mean dose = 12.7 mg/day) and had EPS (Simpson-Angus Scale [SAS] > 3) were directly switched to 6 weeks of open-label olanzapine treatment (mean dose = 11.4 mg/day). There were significant mean improvements (p <0.001 for all measurements) from baseline to endpoint on the SAS (−9.69 ± 5.33; percentage change, 87.2%), the Barnes Akathisia Scale (−1.00 ± 1.19; percentage change, 82.5%), and the Abnormal Involuntary Movement Scale (−1.48 ± 2.89; percentage change, 81.1%), and anticholinergic use decreased from 47.9% to 12.8% (mean baseline to endpoint change: −1.52 ± 1.91-mg equivalents of benztropine;p < 0.001). Significant mean baseline to endpoint improvements (p < 0.001 for all measurements) were observed on the Positive and Negative Syndrome Scale (PANSS; −25.28 ± 18.67; percentage change, 30.3%), the PANSS-extracted Brief Psychiatric Rating Scale (0–6 scale, −13.41 ± 10.16; percent-age change, 54.4%), and the Clinical Global Impressions Severity scale (−1.16 ± 1.19; percentage change, 26.4%). Spontaneously reported treatment-emergent adverse events with a greater than 5% incidence were somnolence (16.0%), increased appetite (14.9%), weight gain (11.7%), headache (8.5%), anxiety (7.4%), dizziness (6.4%), and insomnia (5.3%). Criteria for a successful switch were met by 90.5% of patients. Psychotic symptom exacerbation was experienced by 30.9% of patients at any time during the study and by 11.7% of patients at endpoint. Results suggest that a direct switch to olanzapine is a therapeutic option when patients with haloperidol-induced EPS are unable to tolerate a more gradual switch.
Carcinoembryonic antigen: Clinical correlation with chemotherapy for metastatic gastrointestinal cancer

Serial carcinoembryonic antigen (CEA) titers were measured in 38 patients receiving chemotherapy for metastatic carcinoma of the colon, pancreas, and stomach. CEA levels were initially elevated (over 2.5 ng/ml) in 26 patients (12/20 colonic, 8/10 pancreatic, 6/8 gastric). Seventeen patients had rising serial CEA values during therapy; 13 had evidence of tumor progression, 3 had stable disease, and 1 had no measurable disease. Nineteen patients had stable CEA levels which were either persistently elevated (11 patients) or normal (8 patients). Ten of 11 patients with elevated CEA levels developed tumor progression. In 8 patients with consistently normal CEA levels, 6 (colon) had no evidence of progressive tumor, and 2 (1 pancreatic and 1 gastric) eventually died of metastatic disease. CEA levels decreased in 2 patients with colon carcinoma during remission from chemotherapy. A rising CEA titer often presages clinical deterioration, although elevated CEA levels may remain stable despite progressive disease. Persistently normal CEA, however, is a favorable prognostic sign. The limited effectiveness of chemotherapy for gastrointestinal cancer in this series precludes any definitive conclusion regarding the effect of chemother‐apeutically induced tumor regression on CEA levels, although there is suggestive evidence that CEA correlates with remission.
Psoriatic arthritis and spondyloarthritis assessment and management update

Purpose of reviewThere have been numerous recent advances in our understanding about the epidemiology, pathophysiology, classification, assessment, and emerging treatments and treatment paradigms of psoriatic arthritis (PsA) and spondyloarthritis (SpA). This review provides an update on classification, assessment approaches, and treatments for these conditions. This is timely because it is becoming clear that the prevalence of the spondyloarthritides, including PsA, ankylosing spondylitis, and the broader categories of SpA may be present in 1–2% of the general population, more prevalent than rheumatoid arthritis (RA). Recent findingsThere are new classification criteria of axial and peripheral SpA as well as the CASPAR criteria for PsA, a new composite measure for ankylosing spondylitis and axial SpA, the ASDAS, new measures for the heterogeneous clinical domains of PsA, studies of biologic treatments of axial and peripheral SpA, and new drugs beyond anti-tumor necrosis factors for PsA and SpA. SummaryNew criteria, assessment tools, and therapies will aid research, diagnosis, and timely and targeted treatment to quantitated outcomes for PsA and SpA.
Relation between Relative Cerebral Blood Flow, Relative Cerebral Blood Volume, and Mean Transit Time in Patients with Acute Ischemic Stroke Determined by Perfusion-Weighted MRI

The relation between relative cerebral blood flow (relCBF), relative cerebral blood volume (relCBV), and mean transit time (MTT) changes was examined in 20 patients with acute cerebral ischemia (<6 h) using perfusion-weighted magnetic resonance imaging. Regions of interest (ROI) were selected on MTT maps covering the entire MTT abnormal cortical area. These ROIs were transferred to the relCBF and relCBV maps to analyze the relation between relCBF, relCBV, and MTT on a voxel-by-voxel basis. On the unaffected side, a tight coupling of relCBF and relCBV was found with little variation of MTT. In hypoperfused cortex, relCBV was increased at all investigated relCBF categories, and there was greater relCBV variability than on the unaffected side. Only a severe decrease of relCBF, to less than 0.3, in comparison with the unaffected side was associated with a reduction of relCBV less than 1.0. In contrast to the unaffected side, a power law function (relCBV = 2.283 × relCBF0.549) resulted in a better fit than using a linear function for the correlation of relCBF and relCBV. MTT ratios increased steadily with decreasing CBF values. In conclusion, there is a clear relation between different perfusion-weighted magnetic resonance imaging parameters in acute ischemia, reflecting both the degree of hemodynamic failure as well as compensatory mechanisms including vasodilation.
LED driver with bidirectional series converter for low frequency ripple cancelation

This paper deals with a topology for an off-line LED electronic driver. The use of electrolytic capacitors in the DC link is avoided, therefore extending lifespan and reliability. Given that the resulting output capacitance of the PFC stage is relatively small, a high LF ripple appears at the DC-link. This work proposes the use of a current-fed bidirectional buck converter as a second stage. With the proposed scheme, this stage processes only the AC power corresponding to this voltage ripple, thus increasing the efficiency with respect to a conventional two stage topology. In this approach, the output converter is connected in series with the LEDs assembly, yielding to low voltage stresses at the stage. With a given current control, this scheme ensures a constant current through the LEDs, and ability for AM and PWM dimming operation. A design procedure is shown, and the theoretical results have been validated in a built prototype for a 65W LEDs lamp.
Study of the decomposition of c-C4F8 and its mixture with N2 under 50Hz ac corona discharge

Because of its high dielectric strength, good partial discharge capability, low global warming potential (GWP), none ozone depletion potential (ODP) and no toxicity, fluorocarbon gases(c-C4F8 and its mixture with N2) are possible substitute for SF6, and can be used in electrical equipment. Gas insulated switchgears and transformers using fluorocarbon gas mixtures as dielectric and coolant are new promising power transmission and distribution equipment. To establish the foundation for their safe operation and easily maintenance, more studies are required. The decomposition of fluorocarbon gases subjected to 50 Hz ac corona discharges are presented in this paper. The experiments are conducted on the test model which was designed on our own. The gaseous decomposition products formed during the tests are analyzed and assayed by means of gas chromatography/mass spectrometry (GC/MS). The main identified gaseous by-products are: CF<sub>4</sub>, C<sub>2</sub>F<sub>6</sub>, C<sub>2</sub>F<sub>4</sub>, C<sub>3</sub>F<sub>8</sub> and C<sub>3</sub>F<sub>6</sub> for pure c-C<sub>4</sub>F<sub>8</sub> gas and CF<sub>4</sub>, C<sub>2</sub>F<sub>6</sub>, C<sub>2</sub>F<sub>4</sub>, C<sub>3</sub>F<sub>8</sub>, C<sub>3</sub>F<sub>6</sub> and C<sub>2</sub>F<sub>3</sub>N for mixture gas. In particular the influences of current amplitude, discharge capacity on the formation of main by-products are studied. Meanwhile, the relationship of relative content of decomposition gas with corona discharge amplitude and capacity are obtained. Based on these results and the literature conclusion, criterions for detecting the corona discharge in fluorocarbon insulated equipment is suggested, and it could be helpful to develop a corona discharge diagnostic method for the new type electrical equipment.
Kinetic and pharmacological properties of low voltage-activated Ca2+ current in rat clonal (GH3) pituitary cells.

1. Low voltage-activated (LVA) Ca2+ current in clonal (GH3) pituitary cells was studied with the use of the whole-cell recording technique. The use of internal fluoride to facilitate the rundown of high voltage-activated (HVA) Ca2+ current allowed the study of LVA current in virtual isolation. 2. In 10 mM [Ca2+]o, detectable LVA current begins to appear at about -50 mV, with half-maximal activation occurring at -33 mV. The time course of activation was best described by a Hodgkin-Huxley expression with n = 3, suggesting that at least three closed states must be traversed before channel opening. 3. Deactivation was found to vary exponentially with membrane potential between -60 and -160 mV, indicating that channel closing is rate-limited by a single, voltage-dependent transition. 4. Onset and removal of inactivation between -40 and -130 mV were best described by the sum of two exponentials. Between -80 and -130 mV, both components of removal of inactivation showed little voltage dependence, with time constants of approximately 200-300 ms and 1-2 s. At membrane potentials above -40 mV, a single component of inactivation onset was detected. This component was voltage independent between -20 and +20 mV (tau = 22 ms). Thus inactivation of LVA current is best described by multiple, voltage-in-dependent processes. 5. Significant inactivation of LVA current occurred at -65 mV without detectable macroscopic current. This suggests that inactivation is not strictly coupled to channel opening. 6. Peak LVA current increased with increasing [Ca2+]o, with saturation approximately 50 mM. The Ca(2+)-dependence of peak LVA current was reasonably well described by a single-site binding isotherm with half-maximal LVA current at approximately 7 mM. 7. LVA current in GH3 cells was largely resistant to blockade by Ni2+. The relative potency of inorganic cations in blocking GH3 LVA current was (concentrations which produced 50% block): La3+ (2.4 microM) greater than Cd2+ (188 microM) greater than Ni2+ (777 microM). 8. Several organic agents, including putative LVA blockers, HVA current blockers and various anesthetic agents, were tested for their ability to block LVA current. The concentrations that produced 50% block are as follows: nifedipine (approximately 50 microM), D600 (51 microM), diltiazem (131 microM), octanol (244 microM), pentobarbital (985 microM), methoxyflurane (1.41 mM), and amiloride (1.55 mM). Phenytoin and ethosuximide produced 36 and 10% block at 100 microM and 2.5 mM, respectively. (ABSTRACT TRUNCATED AT 400 WORDS)
Reactive oxygen species and mitochondria mediate the induction of apoptosis in human hepatoma HepG2 cells by the rodent peroxisome proliferator and hepatocarcinogen, perfluorooctanoic acid.

We have previously shown that one of the most potent rodent hepatocarcinogens, perfluorooctanoic acid (PFOA), induces apoptosis in human HepG2 cells in a dose- and time-dependent manner. In this study we have investigated the involvement of reactive oxygen species (ROS), mitochondria, and caspase-9 in PFOA-induced apoptosis. Treatment with 200 and 400 microM PFOA was found to cause a dramatic increase in the cellular content of superoxide anions and hydrogen peroxide after 3 h. Measurement of the mitochondrial transmembrane potential (Delta Psi(m)) after PFOA treatment showed a dissipation of Delta Psi(m) at 3 h. Caspase-9 activation was seen at 5 h after treatment with 200 microM PFOA. In order to evaluate the importance of these events in PFOA-induced apoptosis, cells were cotreated with PFOA and N-acetylcysteine (NAC), a precursor of glutathione, or Cyclosporin A (CsA), an inhibitor of mitochondrial permeability transition pore (MPT pore). NAC reduced Delta Psi(m) dissipation, caspase 9 activation, and apoptosis, indicating a role for PFOA-induced ROS. In addition, CsA also reduced Delta Psi(m) dissipation, caspase 9 activation, and apoptosis, indicating a role for PFOA-induced opening of the MPT pore. In summary, we have delineated a ROS and mitochondria-mediated pathway for induction of apoptosis by PFOA.