Miracle-dz/UniFAR-FTUs huggingface dataset:
Herb-drug interaction between Echinacea purpurea and darunavir/ritonavir in HIV-infected patients

ABSTRACT The aim of this open-label, fixed-sequence study was to investigate the potential of Echinacea purpurea, a commonly used botanical supplement, to interact with the boosted protease inhibitor darunavir-ritonavir. Fifteen HIV-infected patients receiving antiretroviral therapy including darunavir-ritonavir (600/100 mg twice daily) for at least 4 weeks were included. E. purpurea root extract capsules were added to the antiretroviral treatment (500 mg every 6 h) from days 1 to 14. Darunavir concentrations in plasma were determined by high-performance liquid chromatography immediately before and 1, 2, 4, 6, 8, 10, and 12 h after a morning dose of darunavir-ritonavir on days 0 (darunavir-ritonavir) and 14 (darunavir-ritonavir plus echinacea). Individual darunavir pharmacokinetic parameters were calculated by noncompartmental analysis and compared between days 0 and 14 with the geometric mean ratio (GMR) and its 90% confidence interval (CI). The median age was 49 (range, 43 to 67) years, and the body mass index was 24.2 (range, 18.7 to 27.5) kg/m2. Echinacea was well tolerated, and all participants completed the study. The GMR for darunavir coadministered with echinacea relative to that for darunavir alone was 0.84 (90% CI, 0.63-1.12) for the concentration at the end of the dosing interval, 0.90 (90% CI, 0.74-1.10) for the area under the concentration-time curve from 0 to 12 h, and 0.98 (90% CI, 0.82-1.16) for the maximum concentration. In summary, coadministration of E. purpurea with darunavir-ritonavir was safe and well tolerated. Individual patients did show a decrease in darunavir concentrations, although this did not affect the overall darunavir or ritonavir pharmacokinetics. Although no dose adjustment is required, monitoring darunavir concentrations on an individual basis may give reassurance in this setting.
Human Bloodfeeding by the Recently Introduced Mosquito, Aedes japonicus japonicus, and Public Health Implications

Abstract Knowledge of the host-feeding behavior and extent of interactions with human hosts are important in evaluating the role and vector potential of invasive mosquitoes in transmission of native arboviruses. We collected blood-engorged females of the recently established exotic species Aedes japonicus japonicus from sites in New Jersey during 2000 to 2007 and identified the sources of vertebrate blood meals by sequencing portions of the cytochrome b gene of mitochondrial DNA. Over 1/3 (36%, n = 36) of the engorged mosquitoes acquired blood meals from humans. Other mammalian hosts included white-tailed deer (53%), fallow deer (5%), horse (3%), and Virginia opossum (3%). No avian, amphibian, reptilian, or mixed blood meals were identified. Our detection of a comparatively high prevalence of human bloodfeeding in Ae. j. japonicus in association with its local abundance, vector competence, and repeated detection of West Nile virus from field-collected specimens illustrates the potential for this invasive mosquito to serve as a “bridge” vector in transmission of West Nile and other mosquito-borne viruses in North America.
Tranilast suppresses vascular chymase expression and neointima formation in balloon-injured dog carotid artery.

BACKGROUND Activation of vascular chymase plays a major role in myointimal hypertrophy after vascular injury by augmenting the production of angiotensin (ANG) II. Because chymase is synthesized mainly in mast cells, we assumed that the chymase-dependent ANG II formation could be downregulated by tranilast, a mast cell-stabilizing antiallergic agent. We have assessed inhibitory effects of tranilast on neointima formation after balloon injury in the carotid artery of dogs, which share a similar ANG II-forming chymase with humans, and further explored the pathophysiological significance of vascular chymase. METHODS AND RESULTS Either tranilast (50 mg/kg BID) or vehicle was orally administered to beagles for 2 weeks before and 4 weeks after balloon injury. Four weeks after the injury, remarkable neointima was formed in the carotid arteries of vehicle-treated dogs. Chymase mRNA levels and chymaselike activity of vehicle-treated injured arteries were increased 10.2- and 4.8-fold, respectively, those of uninjured arteries. Angiotensin-converting enzyme (ACE) activity was slightly increased in the injured arteries, whereas ACE mRNA levels were not. Tranilast treatment completely prevented the increase in chymaselike activity, reduced the chymase mRNA levels by 43%, and decreased the carotid intima/media ratio by 63%. In vehicle-treated injured arteries, mast cell count in the adventitia showed a great increase, which was completely prevented by the tranilast treatment. Vascular ACE activity and mRNA levels were unaffected by tranilast. CONCLUSIONS Tranilast suppressed chymase gene expression, which was specifically activated in the injured arteries, and prevented neointima formation. Suppression of the chymase-dependent ANG II-forming pathway may contribute to the beneficial effects of tranilast.
Depressed Caregivers: Comparative Outcomes of Two Interventions

A pooled sample of 52 female caregivers (ages 34-78) meeting Research Diagnostic Criteria (RDC) for Major Depressive Dis­ order (MDD) was used to compare response to brief individual verSUS group interventions for depression. Caregivers participating in individ­ ual psychotherapy (n = 28) and caregivers participating in cognitive-he­ ha,ioral groups (n = 24) were compared on changes in Beck Depres­ sion Inventory {BDI) scores and RDC uiagnosis, 10 weeks into each inlervcntiun. While there were no differences between the interventions in BD! scores at 10 weeks, there was greater improvement in RDC di<'lgnosis among the caregivers participating In the cognitive-hchavior~ al groups. The authors suggest that the field is now rcady for random­ ized clinical trials to address this question. fAr/icie copies amilable jiJr a fee from The Haworth Documclll DeliFf! IJ . )'ervice: 1-8{)()-342~9678. E-mail address: gelilifo(Whawurlhpressillc.comj
The future of supernova neutrino detection.

By a series of independent decisions, an international network of massive underground neutrino detectors is being established whose collective sensitivity to supernova neutrinos will be unprecedented. Individually and in coordinated fashion, these detectors could provide temporal, energetic, angular, and flavor information for any stellar collapse in our Galaxy, the Large Magellanic Cloud, or the Small Magellanic Cloud. In this paper, we construct a detailed fiducial model of supernova neutrino bursts that incorporates the numerous emission features derived and predicted by supernova and protoneutron star theorists during the last decade. With this generic model, we calculate and predict the response of representative {hacek C}erenkov and scintillation neutrino telescopes to a nearby neutrino burst. The strengths and weaknesses of the various detectors are highlighted and explored. We focus on the information-rich features of the neutrino signal that were not detectable from SN 1987A. In addition, we investigate the effect of a nonzero neutrino mass on the detected signals. The latter study focuses on what can be derived with {ital high}{minus}{ital resolution} observations of a galactic collapse.
High-Temperature Very Low Frequency Noise-Based Investigation of Slow Transients in AlGaN/GaN MODFETs

The variations of the very low frequency noise (i.e., 100 mHz to 100 kHz) and the dc characteristics of unpassivated AlGaN/GaN modulation-doped field-effect transistors (MODFETs) with temperature from 300 to 500 K are investigated. The rise in temperature to 500 K is shown to reveal generation-recombination (G-R) noise characteristics within the 100 mHz to 1 Hz frequency range. It is experimentally evidenced that these manifestations can predict the existence of very slow transients in the drain-current characteristics of AlGaN/GaN MODFETs. Due to the very long time constant of the transients at room temperature (i.e., on the order of several hours or even days), the observed features can be classified as semipermanent. The comparison between the energy levels predicted by the noise data and the levels previously reported in literature supports these observations.
Serum Circulating microRNA Profiling for Identification of Potential Type 2 Diabetes and Obesity Biomarkers

Background and Aim MicroRNAs are small non-coding RNAs that play important regulatory roles in a variety of biological processes, including complex metabolic processes, such as energy and lipid metabolism, which have been studied in the context of diabetes and obesity. Some particular microRNAs have recently been demonstrated to abundantly and stably exist in serum and to be potentially disease-specific. The aim of this profiling study was to characterize the expression of miRNA in serum samples of obese, nonobese diabetic and obese diabetic individuals to determine whether miRNA expression was deregulated in these serum samples and to identify whether any observed deregulation was specific to either obesity or diabetes or obesity with diabetes. Patients and Methods Thirteen patients with type 2 diabetes, 20 obese patients, 16 obese patients with type 2 diabetes and 20 healthy controls were selected for this study. MiRNA PCR panels were employed to screen serum levels of 739 miRNAs in pooled samples from these four groups. We compared the levels of circulating miRNAs between serum pools of each group. Individual validation of the twelve microRNAs selected as promising biomarkers was carried out using RT-qPCR. Results Three serum microRNAs, miR-138, miR-15b and miR-376a, were found to have potential as predictive biomarkers in obesity. Use of miR-138 or miR-376a provides a powerful predictive tool for distinguishing obese patients from normal healthy controls, diabetic patients, and obese diabetic patients. In addition, the combination of miR-503 and miR-138 can distinguish diabetic from obese diabetic patients. Conclusion This study is the first to show a panel of serum miRNAs for obesity, and compare them with miRNAs identified in serum for diabetes and obesity with diabetes. Our results support the use of some miRNAs extracted from serum samples as potential predictive tools for obesity and type 2 diabetes.
Estimation of the Total Parasite Biomass in Acute Falciparum Malaria from Plasma PfHRP2

Background In falciparum malaria sequestration of erythrocytes containing mature forms of Plasmodium falciparum in the microvasculature of vital organs is central to pathology, but quantitation of this hidden sequestered parasite load in vivo has not previously been possible. The peripheral blood parasite count measures only the circulating, relatively non-pathogenic parasite numbers. P. falciparum releases a specific histidine-rich protein (PfHRP2) into plasma. Quantitative measurement of plasma PfHRP2 concentrations may reflect the total parasite biomass in falciparum malaria. Methods and Findings We measured plasma concentrations of PfHRP2, using a quantitative antigen-capture enzyme-linked immunosorbent assay, in 337 adult patients with falciparum malaria of varying severity hospitalised on the Thai–Burmese border. Based on in vitro production rates, we constructed a model to link this measure to the total parasite burden in the patient. The estimated geometric mean parasite burden was 7 × 1011 (95% confidence interval [CI] 5.8 × 1011 to 8.5 × 1011) parasites per body, and was over six times higher in severe malaria (geometric mean 1.7 × 1012, 95% CI 1.3 × 1012 to 2.3 × 1012) than in patients hospitalised without signs of severity (geometric mean 2.8 × 1011, 95% CI 2.3 × 1011 to 3.5 × 1011; p < 0.001). Parasite burden was highest in patients who died (geometric mean 3.4 × 1012, 95% CI 1.9 × 1012 to 6.3 × 1012; p = 0.03). The calculated number of sequestered parasites increased with disease severity and was higher in patients with late developmental stages of P. falciparum present on peripheral blood smears. Comparing model and laboratory estimates of the time of sequestration suggested that admission to hospital with uncomplicated malaria often follows schizogony—but in severe malaria is unrelated to stage of parasite development. Conclusion Plasma PfHRP2 concentrations may be used to estimate the total body parasite biomass in acute falciparum malaria. Severe malaria results from extensive sequestration of parasitised erythrocytes.
Molecular Characterization of Covalent Complexes between Tissue Transglutaminase and Gliadin Peptides*

Tissue transglutaminase (TG2) modifies proteins and peptides by transamidation or deamidation of specific glutamine residues. TG2 also has a central role in the pathogenesis of celiac disease. The enzyme is both the target of disease-specific autoantibodies and generates deamidated gliadin peptides recognized by intestinal T cells from patients. Incubation of TG2 with gliadin peptides also results in the formation of covalent TG2-peptide complexes. Here we report the characterization of complexes between TG2 and two immunodominant gliadin peptides. Two types of covalent complexes were found; the peptides are either linked via a thioester bond to the active site cysteine of TG2 or via isopeptide bonds to particular lysine residues of the enzyme. We quantified the number of gliadin peptides bound to TG2 under different conditions. After 30 min of incubation of TG2 at 1 μm with an equimolar ratio of peptides to TG2, approximately equal amounts of peptides were bound by thioester and isopeptide linkage. At higher peptide to TG2 ratios, more than one peptide was linked to TG2, and isopeptide bond formation dominated. The lysine residues in TG2 that act as acyl acceptors were identified by matrix assisted laser desorption ionization and nanoelectrospray mass spectrometry and tandem mass spectrometry analysis of proteolytic digests of the TG2-peptide complexes. At a high molar excess of gliadin peptides to TG2 altogether six lysine residues of TG2 were found to participate in isopeptide bond formation. The results are relevant to the understanding of how antibodies to TG2 are formed in celiac disease.
Behavioural evidence for a sleep-like quiescent state in a pulmonate mollusc, Lymnaea stagnalis (Linnaeus)

SUMMARY The objective of this study was to determine whether the great pond snail, Lymnaea stagnalis, expresses a sleep-like behavioural state. We found that snails spontaneously enter a relatively brief (22±1 min) quiescent state characterized by postural relaxation of the foot, mantle and tentacles, and cessation of radula rasping. Quiescence was reversed (‘aroused’) by appetitive (sucrose solution) and aversive (tactile) stimuli. Responsiveness to both stimuli was significantly lower in quiescent snails than in active snails. However, tactile stimuli evoked a more sustained defensive response in quiescent snails. Quiescence bouts were consolidated into ‘clusters’ over an infradian timescale and were only weakly affected by time of day. Clusters contained 7±0.5 bouts, lasted 13±1 h and were separated by long (37±4 h) intervals of almost continuous activity. Analysis of Kaplan–Meier survival curves revealed that the quiescent bout duration was described by an exponential probability distribution (time constant 15±1 min). Active bout duration was described by a bi-exponential probability distribution (time constants 62±4 and 592±48 min). We found no evidence for a ‘sleep rebound’ mechanism and quiescence expression appeared to be regulated through stochastic processes causing state transitions to resemble a Markovian random walk. We conclude that Lymnaea is a potentially valuable model system for studies of cellular function in sleep.
Buccal mucosa is a promising graft in Peyronie's disease surgery. Our experience and a brief literature review on autologous grafting materials.

AIM Peyronie's Disease (PD) is an under reported acquired benign condition that, at the moment, is not curable with medical therapy. Surgery represent the gold standard of treatment. Surgical approaches are several and they consist in "plication techniques" or plaque incision/excision with grafting of resulting albuginea defect. Among grafting procedures, albuginea defect substitution with autologous materials demonstrated over the years not inferior results respect to heterologous grafts. Buccal mucosa graft (BMG) is not usually emphasized in many review articles and clinical series are yet limited. METHODS We present our experience with seventeen plaque incision procedures and BMG in surgical correction of complex penile curvatures due to PD performed in a period of 30 months. Our analyses was focused on buccal mucosa graft characteristics as major determinant of the surgical success. We also conducted a brief literature review on autologous grafting materials used in reconstructive penile surgery for PD. RESULTS Our cosmetics and functional results consists in a 100% of functional penile straightening with no relapses and 5,8% of de novo erectile dysfunction. Mean age was 56.4 years, mean follow-up of 22.5 (6-36) months. No complications graft related were observed. Operative time was 115.3 minutes in mean. Over 94% of patients referred they were "really much better" and "much better" satisfied based on PGI-I questionnaire administrated at the last follow- up visit. CONCLUSION BMG is revealing as an optimal choice for reconstructive surgery in PD. Anatomical characteristics consisting in the great elasticity, the quick integration time and the easy harvesting technique lead to high cosmetics and functional success rate, without omitting economical and invasiveness aspects.
Optimal Consumption and Savings with Stochastic Income and Recursive Utility

We develop a tractable incomplete-markets model with an earnings process Y subject to permanent shocks and borrowing constraints. Financial frictions cause the marginal (certainty equivalent) value of wealth W to be greater than unity and decrease with liquidity w=W/Y. Additionally, financial frictions cause consumption to decrease with this endogenously determined marginal value of liquidity. Risk aversion and the elasticity of inter-temporal substitution play very different roles on consumption and the dispersion of w. Permanent earnings shocks, especially large discrete stochastic jumps, make consumption smoothing quantitatively difficult to achieve. Borrowing constraints and permanent discrete jump shocks can generate empirically plausible values for marginal propensities to consume in the range of 0.2 to 0.6.
Physiological Markers of Interpersonal Stress Generation in Depression

Abnormalities in parasympathetic nervous system activity have been linked to depression, but less is known about processes underlying this relationship. The present study evaluated resting and stress-reactive respiratory sinus arrhythmia (RSA) to a laboratory stressor as predictors of daily interpersonal stress generation and depressive symptoms, whether stress generation mediated the relationship between RSA and depressive symptoms, and potential sex differences. A sample of formerly depressed 102 emerging adults (18–22 years; 79% female) completed a laboratory stressor and daily assessments of stressors and depressive symptoms over 2 weeks. Multilevel modeling revealed that (a) lower resting RSA predicted daily depressive symptoms, (b) less RSA reactivity predicted interpersonal stress generation, (c) interpersonal dependent stressors mediated the relationship between RSA reactivity and daily depressive symptoms, and (d) sex differences occurred in the resting RSA-depression relationship. These findings highlight the importance of resting RSA and RSA reactivity in the examination of depression and interpersonal processes.
Dopamine D2 Receptor Overexpression Alters Behavior and Physiology in Drd2-EGFP Mice

Bacteria artificial chromosome (BAC) transgenic mice expressing the reporter protein enhanced green fluorescent protein (EGFP) under the control of the D1 and D2 dopamine receptor promoters (Drd1-EGFP and Drd2-EGFP) have been widely used to study striatal function and have contributed to our understanding of the physiological and pathological functions of the basal ganglia. These tools were produced and promptly made available to address questions in a cell-specific manner that has transformed the way we frame hypotheses in neuroscience. However, these mice have not been fully characterized until now. We found that Drd2-EGFP mice display an ∼40% increase in membrane expression of the dopamine D2 receptor (D2R) and a twofold increase in D2R mRNA levels in the striatum when compared with wild-type and Drd1-EGFP mice. D2R overexpression was accompanied by behavioral hypersensitivity to D2R-like agonists, as well as enhanced electrophysiological responses to D2R activation in midbrain dopaminergic neurons. Dopamine (DA) transients evoked by stimulation in the nucleus accumbens showed slower clearance in Drd2-EGFP mice, and cocaine actions on DA clearance were impaired in these mice. Thus, it was not surprising to find that Drd2-EGFP mice were hyperactive when exposed to a novel environment and locomotion was suppressed by acute cocaine administration. All together, this study demonstrates that Drd2-EGFP mice overexpress D2R and have altered dopaminergic signaling that fundamentally differentiates them from wild-type and Drd1-EGFP mice.
Overhydration during Transurethral Resection of the Prostate Using Glycine as an Irrigating Solution

The syndrome associated with water intoxication due to absorption of irrigating fluid during transurethral resection of the prostate is well documented. -3 Absorption of large volumes of irrigating fluid may lead to hyponatraemia, haemolysis, pulmonary and cerebral oedema. Haemolysis has since proved to be less of a problem since near isotonic fluids have been used for irrigation. We would like to report a case of water intoxication following 30 minutes of bladder irrigation with 1.5070 glycine solution during a prostate resection that was being performed under spinal anaesthesia.
Mapping the Social Capital Research in Communication

To examine how communication scholars have incorporated the concept of social capital originating from other disciplines, we first analyzed citation patterns among social capital–related journal articles, book chapters, and books extracted from Communication Abstracts. Moreover, we investigated whether and how communication scholars have cited three pioneering scholars in this area, that is, Robert Putnam, Pierre Bourdieu, and James Coleman, to identify aspects of social capital that have either been emphasized or overlooked. Based on the analyses of 171 journal articles, books, and book chapters, we found that the translation of the concept of social capital into communication research has been driven and dominated by a small group of political communication scholars. The results of our content analysis demonstrate that the prominent players in social capital research in the communication field distinctly favored the work of Putnam over those of Bourdieu and Coleman. The implications of these findings for communication research are discussed.