Miracle-dz/UniFAR-FTUs huggingface dataset:
Voltage-dependent block of neuronal and skeletal muscle sodium channels by thymol and menthol.

BACKGROUND AND OBJECTIVE Thymol is a naturally occurring phenol derivative used in anaesthetic practice as a stabilizer and preservative of halothane, usually at a concentration of 0.01%. Although analgesic effects have long been described for thymol and its structural homologue menthol, a molecular basis for these effects is still lacking. We studied the blocking effects of thymol and menthol on voltage-activated sodium currents in vitro as possible molecular target sites. METHODS Whole cell sodium inward currents via heterologously (HEK293 cells) expressed rat neuronal (rat type IIA) and human skeletal muscle (hSkM1) sodium channels were recorded in the absence and presence of definite concentrations of either thymol or menthol. RESULTS When depolarizing pulses to 0 mV were started from a holding potential of -70 mV, half-maximum blocking concentrations (IC50) for the skeletal muscle and the neuronal sodium channel were 104 and 149 mumol for thymol and 376 and 571 mumol for menthol. The blocking potency of both compounds increased at depolarized holding potentials with the fraction of inactivated channels. The estimated dissociation constant Kd for thymol and menthol from the inactivated state was 22 and 106 mumol for the neuronal and 23 and 97 mumol for the skeletal muscle sodium channel, respectively. CONCLUSIONS The results suggest that antinociceptive and local anaesthetic effects of thymol and menthol might be mediated via blockade of voltage-operated sodium channels with the phenol derivative thymol being as potent as the local anaesthetic lidocaine.
An Analysis of Commodity Price Dynamics with Focus on the Price of Salmon

Salmon prices exhibit substantial volatility. An understanding of the structure of volatility is of great interest since this is a major contributor to economic risk in the salmon industry. The volatility process in salmon prices was analysed based on weekly price data from 1995 to 2007. The Generalized Autoregressive Conditional Heteroskedasticity (GARCH) model was used to test for volatility clustering and persistence for prices. We find evidence for and discuss the degree of persistence and reversion in salmon price volatility. Further, we find that volatility is larger in periods of high prices. For the industry this means that larger expected profits more often than not comes at a trade-off of larger price risk.
Critical and Differential Roles of NKp46- and NKp30-Activating Receptors Expressed by Uterine NK Cells in Early Pregnancy1

In early human pregnancy, uterine decidual NK cells (dNK) are abundant and considered as cytokine producers but poorly cytotoxic despite their cytolytic granule content, suggesting a negative control of this latter effector function. To investigate the basis of this control, we examined the relative contribution to the cytotoxic function of different activating receptors expressed by dNK. Using a multicolor flow cytometry analysis, we found that freshly isolated dNK exhibit a unique repertoire of activating and inhibitory receptors, identical among all the donors tested. We then demonstrated that in fresh dNK, mAb-specific engagement of NKp46-, and to a lesser extent NKG2C-, but not NKp30-activating receptors induced intracellular calcium mobilization, perforin polarization, granule exocytosis and efficient target cell lysis. NKp46-mediated cytotoxicity is coactivated by CD2 but dramatically blocked by NKG2A coengagement, indicating that the dNK cytotoxic potential could be tightly controlled in vivo. We finally found that in dNK, mAb-specific engagement of NKp30, but not NKp46, triggered the production of IFN-γ, TNF-α, MIP-1α, MIP-1β, and GM-CSF proinflammatory molecules. These data demonstrate a differential, controlled role of NKp46- and NKp30-activating receptors expressed by dNK that could be critical for the outcome of pregnancy and the killing of uterine cells infected by pathogens.
Effects of Various CYP2D6 Genotypes on the Steady-State Plasma Concentrations of Risperidone and Its Active Metabolite, 9-Hydroxyrisperidone, in Japanese Patients With Schizophrenia

The effects of various CYP2D6 genotypes on the steady-state plasma concentrations (Css) of risperidone and its active metabolite, 9-hydroxyrisperidone, were studied in 85 Japanese schizophrenic patients (27 men and 58 women) treated with 6 mg/d risperidone for at least 2 weeks. Plasma concentrations of risperidone and 9-hydroxyrisperidone were measured using liquid chromatography–tandem mass spectrometry. The patients had the following CYP2D6 genotypes: wild-type (wt) /wt (40 patients), CYP2D6 * 10 (* 10)/ wt (28), CYP2D6 * 5 (* 5)/ wt (8), * 10/ * 10 (5), * 5/ * 10 (3), and CYP2D6 * 4/CYP2D6 * 14 (1), respectively. The Css values of risperidone and 9-hydroxyrisperidone were corrected to the median body weight of 58 kg. The medians (ranges) of the Css of risperidone in the aforementioned genotype groups were 2.2 (0.37–35.7), 6.4 (2.1–26.5), 12.3 (4.7–39.5), 19.4 (13.4–26.4), 64.0 (41.6–68.8), and 91.8 nmol/L. Those values for risperidone-to-9-hydroxyrisperidone ratio were 0.03 (0.01–0.33), 0.06 (0.03–0.19), 0.14 (0.07–0.29), 0.28 (0.25–0.38), 0.48 (0.38–0.58), and 2.35, respectively. The Css of risperidone was significantly (P < 0.05 or P < 0.001) different among the four genotype groups (wt/wt, * 10/wt, * 5/wt, and * 10/ * 10), except between the * 5/wt and * 10/ * 10 groups. Also, the risperidone-to-9-hydroxyrisperidone ratio significantly (P < 0.005 or P < 0.001) differed among these genotype groups. No significant differences were found in the Css of 9-hydroxyrisperidone and the active moiety (the Css of risperidone plus 9-hydroxyrisperidone) among these genotype groups. This study confirms previous findings that the CYP2D6 status affects the Css of risperidone via its strong regulation of 9-hydroxylation of risperidone. However, similar active moiety of risperidone among different genotype groups suggests that the determination of the CYP2D6 genotype has little importance for clinical situations.
The Financial Experience of Hospitals with HMO Contracts: Evidence from Florida

In this paper, we report results from the first study to systematically examine trends in the financial experience of hospitals with health maintenance organization (HMO) contracts. The longitudinal analysis (1990 through 1997) focused on hospitals in Florida. Hospital operating margins for HMO contracts grew tighter toward the end of the study period when the median margin was less than 1%. Teaching hospitals had operating margins that on average were below that of their nonteaching counterparts. The continued growth of HMOs and other managed care entities may have important implications for the future financial viability of U.S. hospitals.
Effect of [Cl−]i on ENaC activity from mouse cortical collecting duct cells

Na+ transport via epithelial Na+ channel (ENaC) occurs across many epithelial surfaces and plays a key role in regulating salt and water absorption. In this study, we have examined the effects of cytosolic Na+ and Cl− on ENaC activity by patch clamping single channel recording method in mouse cortical collecting duct cells (M1). Cytosolic Na+ exerts its effect in change of ENaC open probability (Po). High cytosolic Na+ significantly reduces ENaC Po. No change in channel conductance by cytosolic Na+ is observed. However, decrease of cytosolic Cl− concentration significantly increases channel conductance and ENaC Po. This effect is due to the right shift of ENaC I–V curve to positive membrane potential. The virtue of ENaC conductance remains the same. Cl− channels like CFTR and VRAC are unlikely to be involved in this regulation. The results suggest that cytosolic Cl− could serve as a mediator to regulate ENaC activity, in accordance with the activities of Cl− channels. J. Cell. Physiol. 216: 453–457, 2008. © 2008 Wiley‐Liss, Inc.
Evaluation of the thyroid in patients with hearing loss and enlarged vestibular aqueducts.

OBJECTIVE To evaluate thyroid structure and function in patients with enlargement of the vestibular aqueduct (EVA) and sensorineural hearing loss. DESIGN Prospective cohort survey. SETTING National Institutes of Health Clinical Center, a federal biomedical research facility. PATIENTS The study population comprised 80 individuals, aged 1.5 to 59 years, ascertained on the basis of EVA and sensorineural hearing loss. MAIN OUTCOME MEASURES Associations among the number of mutant alleles of SLC26A4; volume and texture of the thyroid; percentage of iodine 123 ((123)I) discharged at 120 minutes after administration of perchlorate in the perchlorate discharge test; and peripheral venous blood levels of thyrotropin, thyroxine, free thyroxine, triiodothyronine, thyroglobulin, antithyroid peroxidase and antithyroglobulin antibodies, and thyroid-binding globulin. RESULTS Thyroid volume is primarily genotype dependent in pediatric patients but age dependent in older patients. Individuals with 2 mutant SLC26A4 alleles discharged a significantly (P < or = .001) greater percentage of (123)I compared with those with no mutant alleles or 1 mutant allele. Thyroid function, as measured by serologic testing, is not associated with the number of mutant alleles. CONCLUSIONS Ultrasonography with measurement of gland volume is recommended for initial assessment and follow-up surveillance of the thyroid in patients with EVA. Perchlorate discharge testing is recommended for the diagnostic evaluation of patients with EVA along with goiter, nondiagnostic SLC26A4 genotypes (zero or 1 mutant allele), or both.
The case for investment in technology to manage the global costs of dementia

Worldwide growth in the number of people living with dementia will continue over the coming decades and is already putting pressure on health and care systems, both formal and informal, and on costs, both public and private. One response could be to make greater use of digital and other technologies to try to improve outcomes and contain costs. We were commissioned to examine the economic case for accelerated investment in technology that could, over time, deliver savings on the overall cost of care for people with dementia. Our short study included a rapid review of international evidence on effectiveness and cost-effectiveness of technology, consideration of the conditions for its successful adoption, and liaison with people from industry, government, academic, third sector and other sectors, and people with dementia and carers. We used modelling analyses to examine the economic case, using the UK as context. We then discussed the roles that state investment or action could play, perhaps to accelerate use of technology so as to deliver both wellbeing and economic benefits.
Leptin Receptor Expression in the Rat Placenta: Changes in Ob-Ra, Ob-Rb, and Ob-Re with Gestational Age and Suppression by Glucocorticoids1

Abstract Leptin, the hormone product of the ob gene, has recently been implicated as an important player in the complex hormonal control of fetal growth. Leptin actions are mediated via the long isoform of its receptor (Ob-Rb), while shorter isoforms may serve as transporters of leptin through physiological barriers (Ob-Ra) or as leptin-binding proteins in plasma (Ob-Re). Placental expression of these receptor isoforms could thus mediate leptin actions within the placenta or regulate transport of maternal, placental, and fetal leptin. In the present study, we show by real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) that Ob-Ra, Ob-Rb, and Ob-Re mRNAs are dynamically expressed in the functionally distinct basal and labyrinth zones of the rat placenta during the period of maximal fetal growth (i.e., from Day 16 to Day 22 of pregnancy; term = Day 23). Western blot analyses confirmed placental expression of the Ob-Rb protein, and immunolocalization was most prominent in trophoblast and vascular tissues of the labyrinth zone. Ob-Ra and Ob-Re mRNA expression increased markedly (P < 0.01) from Day 16 to Day 22 in the labyrinth but not in the basal zone, whereas Ob-Rb mRNA and protein remained relatively stable. Because glucocorticoids inhibit feto-placental growth, placental leptin receptor (Ob-R) expression was also measured after manipulation of feto-placental glucocorticoid exposure. Maternal treatment with dexamethasone reduced (P < 0.05) placental expression of Ob-Rb mRNA and protein, whereas metyrapone (an inhibitor of glucocorticoid synthesis) stimulated (P < 0.01) placental expression of mRNAs encoding all three Ob-R isoforms. Dexamethasone and carbenoxolone (an inhibitor of the enzyme 11β-hydroxysteroid dehydrogenase) also markedly reduced (P < 0.01) fetal but not maternal plasma leptin concentrations, consistent with inhibition of transplacental passage of maternal leptin. In conclusion, our data indicate that placental expression of Ob-Ra, Ob-Rb, and Ob-Re is likely to mediate leptin action and transport in the fetus and placenta. The effects of glucocorticoid manipulations on placental expression of these isoforms suggest that glucocorticoid-induced feto-placental growth retardation could be mediated, in part, via inhibition of leptin action or transport in the placenta.
Serum IGF-I is higher in gymnasts than runners and predicts bone and lean mass.

INTRODUCTION We examined the relationships between insulin-like growth factor I (IGF-I), its binding protein (IGFBP-3), body composition, and bone mineral density (BMD) in collegiate runners (N = 13), gymnasts (N = 10), and noncompetitive women (N = 10). METHODS Subjects were evaluated by dual-energy x-ray absorptiometry for body composition and BMD of the spine, hip, and whole body, fasting serum levels of IGF-I and IGFBP-3, and dietary intake. The ratio IGF-I/IGFBP-3 was calculated as a marker of IGF-I bioavailability. RESULTS In ANOVA, IGF-I and IGF-I/IGFBP-3 in athletes with oligomenorrhea and amenorrhea did not differ from eumenorrheic athletes; thus, values were pooled. Lean/height2 and bone mass at the hip and spine were higher in gymnasts than runners and controls. Total caloric intake was similar between groups. IGF-I and IGF-I/IGFBP-3 differed between groups with gymnasts having higher IGF-I values than runners (397+/-58 vs 288+/-73 ng x mL(-1), P < 0.001) and higher IGF-I/IGFBP-3 than controls and runners (0.065+/-0.009 vs 0.056+/-0.008 vs 0.045+/-0.009, P = 0.0001). In simple regression, IGF-I and IGF-/IGFBP-3 were related to lean/height2 and BMD of the lumbar spine and hip (P < 0.01-0.0001). IGF-I and IGF-I/IGFBP-3 were multicollinear; thus, the ratio was used in subsequent stepwise regression. Lean mass, corrected for body surface area (height2), independently predicted spine and trochanteric BMD (R2 = 0.26, 0.28, respectively), whereas IGF-I/IGFBP-3 and lean/height2 together contributed to 48% of the variance in femoral neck BMD. CONCLUSION We conclude that, in this group of young adult women, lower BMD in runners may be due, in part, to lower levels of IGF-I and the ratio of IGF-I-to-IGFBP-3 and that IGF-I may mediate the relationship between bone and lean mass.
Characterization of the dopaminergic regulation of human prolactin-secreting cells cultured on extracellular matrix.

Human PRL-secreting adenoma cells were cultured on an extracellular matrix (ECM) secreted by bovine corneal endothelial cells, and their sensitivity to dopamine and dopaminergic agonists was examined. Cells plated on ECM attach rapidly, adopt a flattened morphology, and maintain stable PRL secretion for several weeks. Dopamine inhibited PRL secretion from tumor and nontumor cells on ECM in a dosedependent fashion, with IC50 values of 243 ± 29 and 76 ± 3.3 nM, respectively, and a maximal inhibition of 80% at 10-5 M. Apomorphine (APO), dihydroergocryptine (DHE), and bromocriptine (CB-154) also inhibited PRL secretion from adenoma cells in a dose-dependent fashion, with IC50 values of 24 ± 13, 0.35 ± 0.1, and 0.05 ± 0.01 nM, respectively. Thus, the rank order of potency of the dopamine agonists in inhibiting PRL secretion from adenoma cells was consistent with an interaction at a dopamine receptor: CB-154 > DHE > APO > dopamine. The dopamine antagonists, D-butaclamol, spiperone, domperidone, chlorpromazine, .
Consumer Willingness to Pay for Dairy Products With the 100% Canadian Milk Label: A Discrete Choice Experiment

ABSTRACT A component of the supply management policy governing the Canadian dairy sector is a requirement that all milk and cream sold in Canada be sourced from Canadian producers. Cheese, yogurt, and ice cream, however, can be made using imported milk components. Recently, the Dairy Farmers of Canada launched a 100% Canadian Milk label for products that contain only milk and milk ingredients produced in Canada. Featuring a discrete choice experiment, a Canada-wide survey of dairy consumers is used to elicit their willingness-to-pay for milk and ice cream carrying the 100% Canadian Milk label. The results show that Canadian consumers are willing to pay more for milk and ice cream products that carry the label. Consumer knowledge of the dairy sector affects their willingness to pay for this labeling information. Implications for the use of the Canadian origin label and suggestions for further research are discussed.
Ekonomik Özgürlüklerin İktisadi Büyüme Üzerindeki Etkileri: Bir Panel Veri Analizi

Son otuz yildan bu yana yasanan en onemli gelismelerden biri, hizlanan kuresellesme hareketleri kapsaminda liberal iktisadi dusunce ve politikalarin dunya genelinde yayilmasi olmustur. Ozellikle neoliberal hareketler ile birlikte iktisadi bakimdan kapsami genisletilen ozgurlukcu akimlar, toplumsal yapilanma tarafindan vazgecilmez bir unsur olmus ve ekonomik serbesti, refah gucunun artirilabilmesi amaciyla makro iktisadi gelismelerin ana eksenini olusturmustur. Dolayisiyla bu calismada, ekonomik ozgurlukler ile ekonomik buyume arasindaki iliskiler 1995 – 2012 doneminde gelismis, gelismekte olan ve azgelismis ekonomiler icin panel veri analizleri kullanilarak arastirilmistir. Pedroni ve Kao esbutunlesme analiz sonuclari, ekonomik ozgurlukler ile iktisadi buyume arasinda uzun donemli iliskilerin varligini gostermistir. Ayrica, Granger nedensellik analiz bulgulari ise ekonomik ozgurluklerin, iktisadi buyumenin nedeni oldugunu yansitmistir. Analiz sonuclari bir butun olarak degerlendirildiginde ekonomik ozgurluklerin iktisadi buyume surecini hizlandirdigini soylemek mumkundur.
Hepatitis B vaccine effectiveness in the face of global HBV genotype diversity

Recombinant hepatitis B vaccines are of the A2 genotype; one of ten known genotypes whose distribution varies globally. Reports of rare HBV infections in blood donors with an imbalance of non-A2 genotype HBV in vaccinated subjects have raised questions about the cross-protection afforded by HBV-A2 vaccines. Infections in HBV vaccinees were asymptomatic and transient, indicating that vaccination prevented clinical disease. Preclinical data demonstrate cross-reactivity and cross-protection by A2 vaccines against non-A2 HBV genotypes. Substantial improvements in HBV control have been demonstrated in countries with diverse genotype distribution that have introduced universal childhood HBV vaccination programs. Available data show that current HBV-A2 vaccines are highly effective in preventing infections and clinical disease caused by all known HBV genotypes.
Frozen chicken for wild fish: Nutritional transition in the Brazilian Amazon region determined by carbon and nitrogen stable isotope ratios in fingernails

Amazonian populations are experiencing dietary changes characteristic of the nutrition transition. However, the degree of change appears to vary between urban and rural settings. To investigate this process, we determined carbon and nitrogen stable isotope ratios in fingernails and dietary intake of Amazonian populations living along a rural to urban continuum along the Solimões River in Brazil.
Stat 1 Is Induced and Activated by All-Trans Retinoic Acid in Acute Promyelocytic Leukemia Cells

Treatment of freshly isolated acute promyelocytic leukemia gene, in the presence of the RARa retinoic acid receptor, but (APL) cells and the myelogenous leukemia cell lines, NB4, not in the presence of the PML-RAR protein. Treatment of HL-60, and U937, with all-trans retinoic acid (ATRA) results NB4 cells with ATRA is associated with a remarkable upreguin a remarkable elevation in the amounts of Stat1a and Stat2 lation of the two IFN-responsive genes IFN-responsive factor proteins. Stat1a protein levels are augmented by ATRA as 1 and 2*-5* oligoadenylate synthetase, as well as with an a consequence of elevated amounts of the corresponding augmentation in the levels of IFNa secretion. Our data show transcripts. The retinoid increases the levels of nuclear comthat ATRA is capable of modulating the amounts and the plexes that are capable of binding to interferon (IFN)-regustate of activation of some of the components of the IFN lated consensus sequences and contain Stat1 and/or Stat2 intracellular signaling pathways. They also suggest that the proteins, and causes a rapid and long-lasting elevation in retinoid can bypass IFN/IFN-receptor interactions and inStat1a tyrosine phosphorylation. Transient transfection exduce the expression of IFN-regulated genes. periments show that ATRA enhances the transactivating q 1997 by The American Society of Hematology. properties of Stat1a observed on an appropriate reporter
Sensitivity of beamformer source analysis to deficiencies in forward modeling

Beamforming approaches have recently been developed for the field of electroencephalography (EEG) and magnetoencephalography (MEG) source analysis and opened up new applications within various fields of neuroscience. While the number of beamformer applications thus increases fast‐paced, fundamental methodological considerations, especially the dependence of beamformer performance on leadfield accuracy, is still quite unclear. In this article, we present a systematic study on the influence of improper volume conductor modeling on the source reconstruction performance of an EEG‐data based synthetic aperture magnetometry (SAM) beamforming approach. A finite element model of a human head is derived from multimodal MR images and serves as a realistic volume conductor model. By means of a theoretical analysis followed by a series of computer simulations insight is gained into beamformer performance with respect to reconstruction errors in peak location, peak amplitude, and peak width resulting from geometry and anisotropy volume conductor misspecifications, sensor noise, and insufficient sensor coverage. We conclude that depending on source position, sensor coverage, and accuracy of the volume conductor model, localization errors up to several centimeters must be expected. As we could show that the beamformer tries to find the best fitting leadfield (least squares) with respect to its scanning space, this result can be generalized to other localization methods. More specific, amplitude, and width of the beamformer peaks significantly depend on the interaction between noise and accuracy of the volume conductor model. The beamformer can strongly profit from a high signal‐to‐noise ratio, but this requires a sufficiently realistic volume conductor model. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.