bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of [Ca2+]i and pH on epithelial Na+ channel activity of cultured mouse cortical collecting ducts
Authors: Gu Yuchun 
Published: September 2008

SUMMARY
[Ca2+]i and pH have been demonstrated to affect Na+ transport in epithelium mediated via the apical epithelial Na+ channel (ENaC). However, it still remains unclear whether the effects of [Ca2+]i and intracellular pH(pHi) on ENaC activity are direct. In this study, inside-out recording was employed to clarify the effects of pHi and[Ca2+]i on ENaC activity. We found that elevation of[Ca2+]i induced a significant inhibition of ENaC open probability without altering channel conductance. The inhibitory effect was due to a direct interaction between Ca2+ and ENaC, and is dependent on [Ca2+]i. pHi also directly regulated ENaC open probability. Lower pHi (&lt;7.0) reduced the ENaC open probability as shown in shorter opening time, and higher pHi(&gt;7.0) enhanced the ENaC open probability as shown in augmented opening time. pHi did not cause any alteration in channel conductance. The effects of pHi on ENaC open probability could be summarized as an S-shaped curve around pH 7.2.
Leg symptoms of healthy people and their treatment with compression hosiery
Authors: Blättler W , Kreis N , Lun B , Winiger J , Amsler F 
Published: September 2008

Objectives Occasional leg symptoms, like feelings of heaviness and tension, and occupational or evening oedema are considered typical features of a venous disorder but show low specificity in epidemiological and observational studies. We evaluated the prevalence and nature of such symptoms in subjects with no history or signs of venous disease and investigated the optimal strength that medical compression stockings (MCS) should exert in order to alleviate the symptoms and to prevent leg swelling. Methods Specifically designed questionnaires were used to assess the symptoms of 40 healthy employees of a factory producing MCS. Lower leg volumes were quantified in the morning and evening. Calf size hosiery providing documented ankle pressures of 4–9 (mean 7.3), 12–18 (mean 14.9) and 18–22 (mean 19.5) mmHg, respectively, were tested in a prospective, open-label, randomized trial lasting three weeks. Endpoints were the relief of symptoms, prevention of vesperal oedema and comfort in wearing the stockings. Results Sixty-five percent of the participants reported at least occasional leg symptoms and oedema. Somatic-type symptoms (i.e. pain, heaviness, swelling, unattractive legs) were present in two, psychic-type symptoms (i.e. leg- and personality-related unrest and stress) in 17 and both components in seven of the 40 subjects. MCS exerting 15 and 20 mmHg prevented the symptoms and oedema. Stockings providing <10 mmHg were ineffective and those providing >19 mmHg were not well-tolerated. The effect on the somatic-type symptoms was strongly correlated with the amount of lower leg volume which could be reduced by wearing stockings ( P = 0.005). No correlation was found between the efficacy of compression and the emotional component of the symptoms. Conclusion The cause of occasional pain in the legs of apparently healthy people is unknown. Some features of the syndrome reflect an emotional disorder while others mirror venous insufficiency. MCS of 15 mmHg effectively relieve the symptoms resembling venous insufficiency, prevent oedema and are well-tolerated.
Simulation-Based Optimization of Virtual Nesting Controls for Network Revenue Management
Authors: van Ryzin Garrett , Vulcano Gustavo 
Published: September 2008

Virtual nesting is a popular capacity control strategy in network revenue management. In virtual nesting, products (itinerary-fare-class combinations) are mapped (“indexed”) into a relatively small number of “virtual classes” on each resource (flight leg) of the network. Nested protection levels are then used to control the availability of these virtual classes; specifically, a product request is accepted if and only if its corresponding virtual class is available on each resource required. Bertsimas and de Boer proposed an innovative simulation-based optimization method for computing protection levels in a virtual nesting control scheme [Bertsimas, D., S. de Boer. 2005. Simulation-based booking-limits for airline revenue management. Oper. Res. 53 90–106]. In contrast to traditional heuristic methods, this simulation approach captures the true network revenues generated by virtual nesting controls. However, because it is based on a discrete model of capacity and demand, the method has both computational and theoretical limitations. In particular, it uses first-difference estimates, which are computationally complex to calculate exactly. These gradient estimates are then used in a steepest-ascent-type algorithm, which, for discrete problems, has no guarantee of convergence. In this paper, we analyze a continuous model of the problem that retains most of the desirable features of the Bertsimas-de Boer method, yet avoids many of its pitfalls. Because our model is continuous, we are able to compute gradients exactly using a simple and efficient recursion. Indeed, our gradient estimates are often an order of magnitude faster to compute than first-difference estimates, which is an important practical feature given that simulation-based optimization is computationally intensive. In addition, because our model results in a smooth optimization problem, we are able to prove that stochastic gradient methods are at least locally convergent. On several test problems using realistic networks, the method is fast and produces significant performance improvements relative to the protection levels produced by heuristic virtual nesting schemes. These results suggest it has good practical potential.
Nutrition Education and Support Program for Community-Dwelling Adults With Intellectual Disabilities
Authors: Humphries Kathleen , Traci Meg Ann , Seekins Tom 
Published: September 2008

AbstractTo test the efficacy, acceptability, and appropriateness of a nutrition education and support program, 4 community-based group homes for adults with intellectual or developmental disabilities participated in a pilot intervention with extended baseline period and pre–post-test design. Adults (N = 32) with intellectual or developmental disabilities, 20 direct service staff, 4 managers of group homes, and 2 health specialists at private service providers participated in the intervention, consisting of a system of nutrition supports in nutrition education and guidelines, menu and meal planning, grocery shopping, and cooking designed for the special needs of this population. Positive impacts were found using the program, including fidelity measures, food systems changes and acceptability to users, planned and served foods, and cost changes associated with implementation.
Embedded, Constant Time Delay Instruction by Peers Without Disabilities in General Education Classrooms
Authors: Jameson J. Matt , McDonnell John , Polychronis Shamby , Riesen Tim 
Published: September 2008

Abstract
This study investigated the effects of a training package (written manual, individual training session, and ongoing verbal feedback) on middle school peer tutors' use of embedded, constant time delay procedures and on the learning outcomes for students with significant cognitive disabilities in general education settings. The study data showed that peer tutors could be trained quickly and efficiently to accurately use constant time delay and embedded instructional techniques in general education settings. The data also showed that peer tutors delivering embedded, constant time delay instruction in general education settings resulted in skill acquisition for students with significant cognitive disabilities. In addition, teacher and peer tutor measures were positive about the social validity of the procedures and outcomes of the peer-delivered embedded instructional package.
Simultaneous Measurement of Serum Testosterone and Dihydrotestosterone by Liquid Chromatography–Tandem Mass Spectrometry
Authors: Shiraishi Steve , Lee Paul W N , Leung Andrew , Goh Victor H H , Swerdloff Ronald S , Wang Christina 
Published: September 2008

Abstract
Background: Recent reports have described inherent problems with androgen immunoassays compared with mass spectrometry analyses.
Methods: We developed a method for measuring serum testosterone (T) and 5α-dihydrotestosterone (DHT) simultaneously via liquid–liquid extraction followed by liquid chromatography–tandem mass spectrometry (LC-MS/MS) with positive-mode electrospray ionization.
Results: The DHT and T calibrators showed a linear response from 0.069 nmol/L to 34.4 nmol/L and 69.3 nmol/L, respectively. T interference in the DHT assay and vice versa were negligible. Within- and between-run imprecision values were &lt;5% for both analytes. Percent recoveries of T and DHT spiked into samples at concentrations spanning the calibration curve were 100%–113% and 98%–107%, respectively. The lower limit of quantification was 0.069 nmol/L for both steroids. Serum T concentrations measured by LC-MS/MS were different from those obtained by RIA, especially at lower T concentrations. Serum DHT concentrations measured by LC-MS/MS were markedly lower than those generated by RIA because of the nonselectivity of the RIA without chromatography. The reference intervals (mean ± 2 SDs) determined for T and DHT were 9.2–33.7 nmol/L and 0.47–2.65 nmol/L, respectively, for 113 healthy adult men and 0.33–2.02 nmol/L and 0.09–0.91 nmol/L, respectively, for 133 healthy premenopausal women.
Conclusions: We have developed and validated a selective and precise method for simultaneous measurements of serum T and DHT that can be adopted for routine measurements of these androgens in health and disease in men and women.
Neuronal Source of Plasma Dopamine
Authors: Goldstein David S , Holmes Courtney 
Published: September 2008

AbstractBackground: Determinants of plasma norepinephrine (NE) and epinephrine concentrations are well known; those of the third endogenous catecholamine, dopamine (DA), remain poorly understood. We tested in humans whether DA enters the plasma after corelease with NE during exocytosis from sympathetic noradrenergic nerves.Methods: We reviewed plasma catecholamine data from patients referred for autonomic testing and control subjects under the following experimental conditions: during supine rest and in response to orthostasis; intravenous yohimbine (YOH), isoproterenol (ISO), or glucagon (GLU), which augment exocytotic release of NE from sympathetic nerves; intravenous trimethaphan (TRI) or pentolinium (PEN), which decrease exocytotic NE release; or intravenous tyramine (TYR), which releases NE by nonexocytotic means. We included groups of patients with pure autonomic failure (PAF), bilateral thoracic sympathectomies (SNS-x), or multiple system atrophy (MSA), since PAF and SNS-x are associated with noradrenergic denervation and MSA is not.Results: Orthostasis, YOH, ISO, and TYR increased and TRI/PEN decreased plasma DA concentrations. Individual values for changes in plasma DA concentrations correlated positively with changes in NE in response to orthostasis (r = 0.72, P &lt; 0.0001), YOH (r = 0.75, P &lt; 0.0001), ISO (r = 0.71, P &lt; 0.0001), GLU (r = 0.47, P = 0.01), and TYR (r = 0.67, P &lt; 0.0001). PAF and SNS-x patients had low plasma DA concentrations. We estimated that DA constitutes 2%–4% of the catecholamine released by exocytosis from sympathetic nerves and that 50%–90% of plasma DA has a sympathoneural source.Conclusions: Plasma DA is derived substantially from sympathetic noradrenergic nerves.
A Personalized Approach to Cancer Treatment: How Biomarkers Can Help
Authors: Duffy Michael J , Crown John 
Published: September 2008

Abstract
Background: The present approach to cancer treatment is often referred to as “trial and error” or “one size fits all.” This practice is inefficient and frequently results in inappropriate therapy and treatment-related toxicity. In contrast, personalized treatment has the potential to increase efficacy and decrease toxicity.
Content: We reviewed the literature relevant to prognostic, predictive, and toxicity-related markers in cancer, with particular attention to systematic reviews, prospective randomized trials, and guidelines issued by expert panels. To achieve personalized treatment for cancer, we need markers for determining prognosis, predicting response to therapy, and predicting severe toxicity related to treatment. Among the best-validated prognostic markers currently available are serum concentrations of α-fetoprotein (AFP), human chorionic gonadotropin (hCG), and lactate dehydrogenase (LDH) for patients with nonseminoma germ cell tumors and tissue concentrations of both urokinase plasminogen activator and plasminogen activator inhibitor 1 (PAI-1) for breast cancer patients. Clinically useful therapy predictive markers are estrogen and progesterone receptors to select patients with breast cancer for treatment with endocrine therapy and human epidermal growth factor receptor 2 (HER-2) to select breast cancer patients for treatment with trastuzumab (Herceptin). Markers available for identifying drug-induced adverse reactions include thiopurine methyltransferase (TPMT) to predict toxicity from thiopurines in the treatment of acute lymphoblastic leukemia and uridine diphosphate glucuronyltransferase to predict toxicity from irinotecan in the treatment of colorectal cancer.
Conclusions: Validated prognostic, predictive, and toxicity markers should help cancer treatment move from the current trial-and-error approach to more personalized treatment.
Monographs on drugs which are frequently analyzed in therapeutic drug monitoring / Arzneimittel-Monographien für Medikamente, die regelmäßig im Rahmen des Therapeutic Drug Monitorings analysiert werden
Authors: Rentsch Working group “Drug Monitoring” of the SSCC: Katharina , Eap Chin Bin , Fathi Marc , Grignaschi Nathalie , Magnin Jean-Luc , Thormann Wolfgang , Todesco Liliane , Werner Dominique 
Published: September 2008

Abstract
In addition to the monographs which have been published recently by the working group “Drug Monitoring” of the Swiss Society of Clinical Chemistry (SSCC) [1, 2], new monographs have been written. The aim of these monographs is to provide an overview on the information which is important for the request and interpretation of the results. Therefore, the targeted readers are laboratory health professionals and the receivers of the reports. In this series, aminoglycoside as well as glycopeptide antibiotics are presented. In addition, two antimycotic drugs, which are regularly quantified in sera of intensive care patients, are described. Also, the monograph on mebendazole is shown. This drug is often used in high doses for the treatment of infections with Echinococcus multilocularis for which the measurement of drug concentrations in serum is recommended. Information on the indication for therapeutic drug monitoring (TDM), protein binding, metabolic pathways and enzymes involved, elimination half-life and elimination routes, and therapeutic or toxic concentrations is provided. Because pre-analytical considerations are of particular importance for therapeutic drug monitoring, there is also information given at which time the determination of the drug concentration is reasonable and when steady-state concentrations are reached after changing the dose. Furthermore, the stability of the drug and its metabolite(s) after blood sampling is described. For readers with a specific interest, references to important publications are provided. The number of the monographs will be continuously increased. The updated files are presented on the homepage of the SSCC (www.sscc.ch). We hope that these monographs are helpful for the better handling of therapeutic drug monitoring and we are looking forward to comments by the readers.
Laboranalytik im Rahmen klinischer Studien unter Berücksichtigung der ICH-GCP-Leitlinie / Laboratory testing in clinical trials under consideration of the ICH-GCP guideline
Authors: Nordmann Stephan , Wieland Eberhard 
Published: September 2008

Zusammenfassung
Klinische Studien sind für die Einführung und Zulassung neuer Arzneimittel unverzichtbar. In den letzten Jahren haben sich die Regeln weltweit und damit auch die gesetzlichen Normen in Deutschland verschärft. Das Arzneimittelgesetz (AMG) hat die Inhalte der international harmonisierten Leitlinie zur Guten Klinischen Praxis (ICH-GCP) übernommen, welche die ethischen und qualitativen Bedingungen zur Durchführung klinischer Studien beschreiben. Da Laboruntersuchungen Bestandteil fast aller klinischen Studien zur Arzneimittelprüfung sind, gelten diese Normen auch für die Laboranalytik im Rahmen klinischer Studien. Unter Berücksichtigung dieser Normen und Gesetze ist zu fordern, dass Laboratorien und Laborärzte schon bei der Planung von klinischen Studien gehört werden sollten. Darüber hinaus sollte das Labor vor dem Beginn einer Studie in einem Prüfzentrum informiert werden. Am besten sollte ein getrennter Laborvertrag abgeschlossen werden und die Laborleistungen für klinische Studien separat nach der Gebührenordnung für Ärzte (GOÄ) honoriert werden. Die Vorlage von Ringversuchszertifikaten und die Bereitstellung eines Leistungsverzeichnisses nach Abschluss einer Studie reichen nach der Meinung der Autoren nicht aus, um dem AMG gerecht zu werden und um das Laborpersonal ausreichend juristisch abzusichern.
Identification of Stem Cells During Prepubertal Spermatogenesis via Monitoring of Nucleostemin Promoter Activity
Authors: Ohmura Masako , Naka Kazuhito , Hoshii Takayuki , Muraguchi Teruyuki , Shugo Haruhiko , Tamase Akira , Uema Noriyuki , Ooshio Takako , Arai Fumio , Takubo Keiyo , Nagamatsu Go , Hamaguchi Isao , Takagi Minoru , Ishihara Masahiko , Sakurada Kazuhiro , Miyaji Hiromasa , Suda Toshio , Hirao Atsushi 
Published: September 2008

Abstract
The nucleostemin (NS) gene encodes a nucleolar protein found at high levels in several types of stem cells and tumor cell lines. The function of NS is unclear but it may play a critical role in S-phase entry by stem/progenitor cells. Here we characterize NS expression in murine male germ cells. Although NS protein was highly expressed in the nucleoli of all primordial germ cells, only a limited number of gonocytes showed NS expression in neonatal testes. In adult testes, NS protein was expressed at high levels in the nucleoli of spermatogonia and primary spermatocytes but at only low levels in round spermatids. To evaluate the properties of cells expressing high levels of NS, we generated transgenic reporter mice expressing green fluorescent protein (GFP) under the control of the NS promoter (NS-GFP Tg mice). In adult NS-GFP Tg testes, GFP and endogenous NS protein expression were correlated in spermatogonia and spermatocytes but GFP was also ectopically expressed in elongated spermatids and sperm. In testes of NS-GFP Tg embryos, neonates, and 10-day-old pups, however, GFP expression closely coincided with endogenous NS expression in developing germ cells. In contrast to a previous report, our results support the existence in neonatal testes of spermatogonial stem cells with long-term repopulating capacity. Furthermore, our data show that NS expression does not correlate with cell-cycle status during prepuberty, and that strong NS expression is essential for the maintenance of germline stem cell proliferation capacity. We conclude that NS is a marker of undifferentiated status in the germ cell lineage during prepubertal spermatogenesis.
Disclosure of potential conflicts of interest is found at the end of this article.
Measuring Hypothetical Bias in Choice Experiments: The Importance of Cognitive Consistency
Authors: Johansson-Stenman Olof , Svedsäter Henrik 
Published: September 2008

Abstract
A choice experiment eliciting environmental values with both real and hypothetical trade-offs is set up in order to test for hypothetical bias. A larger hypothetical bias was found in a between-subject than in a within-subject design, using otherwise identical scenarios, which can explain previous diverging results in the literature. We argue that people strive for consistency between their attitudes and behaviors, leading them to act in ways that correspond with their prior hypothetical statements. People hence seem to prefer to do what they say they would do, although this may not always reflect their true preferences regarding the good being valued.
Dual Role of Interleukin-6 in Regulating Insulin Sensitivity in Murine Skeletal Muscle
Authors: Nieto-Vazquez Iria , Fernández-Veledo Sonia , de Alvaro Cristina , Lorenzo Margarita 
Published: September 2008

OBJECTIVE—Cytokines are elevated in various insulin-resistant states, including type 2 diabetes and obesity, although the contribution of interleukin-6 (IL-6) in the induction of these diseases is controversial.
RESEARCH DESIGN AND METHODS—We analyzed the impact of IL-6 on insulin action in murine primary myocytes, skeletal muscle cell lines, and mice (wild type and protein-tyrosine phosphatase 1B [PTP1B] deficient).
RESULTS—IL-6 per se increased glucose uptake by activating serine/threonine protein kinase 11 (LKB1)/AMP-activated protein kinase/protein kinase B substrate of 160 kDa (AS160) pathway. A dual effect on insulin action was observed when myotubes and mice were exposed to this cytokine: additive with short-term insulin (increased glucose uptake and systemic insulin sensitivity) but chronic exposure produced insulin resistance (impaired GLUT4 translocation to plasma membrane and defects in insulin signaling at the insulin receptor substrate 1 [IRS-1] level). Three mechanisms seem to operate in IL-6–induced insulin resistance: activation of c-Jun NH2-terminal kinase 1/2 (JNK1/2), accumulation of suppressor of cytokine signaling 3 (socs3) mRNA, and an increase in PTP1B activity. Accordingly, silencing JNK1/2 with either small interfering RNA or chemical inhibitors impaired phosphorylation of IRS-1 (Ser307), restored insulin signaling, and normalized insulin-induced glucose uptake in myotubes. When using a pharmacological approach, liver X receptor agonists overcome IL-6–induced insulin resistance by producing downregulation of socs3 and ptp1b gene expression. Finally, the lack of PTP1B confers protection against IL-6–induced insulin resistance in skeletal muscle in vitro and in vivo, in agreement with the protection against the IL-6 hyperglycemic effect observed on glucose and insulin tolerance tests in adult male mice.
CONCLUSIONS—These findings indicate the important role of IL-6 in the pathogenesis of insulin resistance and further implicate PTP1B as a potential therapeutic target in the treatment of type 2 diabetes.