bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacological treatment for the prevention of delirium: review of current evidence
Authors: Tabet Naji , Howard Robert 
Published: February 2009

AbstractObjectiveDelirium is a very common and serious disorder with high morbidity and mortality. Despite symptomatic treatment the outcome can be poor for some especially when no underlying cause is identified. As a result, various strategies for delirium prevention have been assessed. Pharmacological agents such as antipsychotics, acetylcholinesterase inhibitors, sleep–wake cycle regulators, anti‐inflammatories and others have been advocated for a potential role in delirium prevention. The aim of this paper is to review the available evidence for their use in the prevention of delirium.MethodsAn electronic search was carried out using Medline, EMBASE and Cochrane for randomised controlled trials (RCTs) and other studies. The words delirium, prevention, intervention, pharmacological, prophylactic, antipsychotics, acetylcholinesterase inhibitors, sleep and anti‐inflammatories were used. References from selected papers were also searched.ResultsNo multi‐centre RCT has been identified. Few trials and other studies have been published so far assessing the prophylactic role of antipsychotics, acetylcholinesterase inhibitors, hypnotics, melatonin, and gabapentin. As these studies tested different drugs, regimes and protocols in diverse populations no meaningful comparison can be made.ConclusionTo date there is conflicting and inconsistent data regarding the efficacy of pharmacological treatment for delirium prevention. Positive reports in few of the studies justify further assessment of the potential for some pharmacological agents in the prevention of delirium. Well designed and appropriately powered RCTs are now needed. However, based on available evidence so far, no recommendation can be made to justify the routine clinical prophylactic use of any pharmacological agent in the prevention of delirium. Copyright © 2009 John Wiley & Sons, Ltd.
PCSK9 impedes hepatitis C virus infection in vitro and modulates liver CD81 expression #
Authors: Labonté Patrick , Begley Syntia , Guévin Carl , Asselin Marie-Claude , Nassoury Nasha , Mayer Gaétan , Prat Annik , Seidah Nabil G. 
Published: February 2009

Abstract
Human PCSK9 is known to enhance the degradation of membrane-bound receptors such as the hepatocyte low-density lipoprotein receptor (LDLR), ApoER2, and very low-density lipoprotein receptor. Because the LDLR is suspected to be involved in hepatitis C virus (HCV) entry, we also tested whether PCSK9 can affect the levels of CD81, a major HCV receptor. Interestingly, stable expression of PCSK9 or a more active membrane-bound form of the protein (PCSK9-ACE2) resulted in a marked reduction in CD81 and LDLR expression. Therefore, we analyzed the antiviral effect of PCSK9 in vitro using the HCV genotype 2a (JFH1) virus. The results clearly demonstrated that cells expressing PCSK9 or PCSK9-ACE2, but not the ACE2 control protein, were resistant to HCV infection. Furthermore, addition of purified soluble PCSK9 to cell culture supernatant impeded HCV infection in a dose-dependent manner. As expected, HuH7 cells expressing PCSK9-ACE2 were also resistant to infection by HCV pseudoparticles. In addition, we showed that CD81 cell surface expression is modulated by PCSK9 in an LDLR-independent manner. Finally, in the liver of single Pcsk9 and double (Pcsk9 + Ldlr) knockout mice, both LDLR and/or CD81 protein expression levels were significantly reduced, but not those of transferrin and scavenger receptor class B type 1. Conclusion: Our results demonstrate an antiviral effect of the circulating liver PCSK9 on HCV in cells and show that PCSK9 down-regulates the level of mouse liver CD81 expression in vivo. Therefore, we propose that the plasma level and/or activity of PCSK9 may modulate HCV infectivity in humans. (Hepatology 2009.)
S6K1 deficiency protects against apoptosis in hepatocytes #
Authors: González-Rodriguez Águeda , Alba Javier , Zimmerman Valeri , Kozma Sara C. , Valverde Ángela M. 
Published: February 2009

Abstract
The mammalian target of rapamycin (mTOR)/S6K1 signaling pathway controls cell growth and proliferation. To assess the importance of S6K1 in the balance between death and survival in the liver, we have generated immortalized hepatocyte cell lines from wild-type and S6K1-deficient (S6K1−/−) mice. In S6K1−/− hepatocytes, caspase-8 and the pro-apoptotic protein Bid were constitutively down-regulated as compared with wild-type. Moreover, S6K1−/− hepatocytes failed to respond to the apoptotic trigger of death receptor activation. Neither caspase-8 activation nor FLIPL degradation in response to tumor necrosis factor alpha (TNF-α) or anti-Fas antibody (Jo2) was observed in cells lacking S6K1. Downstream events such as Bid cleavage, cytochrome C release, caspase-3 activation, DNA laddering, as well as the percentage of apoptotic cells were attenuated as compared with wild-type. In addition, the anti-apoptotic protein BclxL was down-regulated in TNF-α–treated or Jo2-treated wild-type hepatocytes, but this response was abolished in S6K1−/−cells. In vivo, S6K1-deficient mice were protected against concanavalin A–induced apoptosis. The withdrawal of growth factors strongly induced apoptosis in wild-type, but not in S6K1−/− hepatocytes. S6K1 deficiency did not decrease BclxL/Bim ratio on serum withdrawal, thereby protecting cells from cytochrome C release and DNA fragmentation. At the molecular level, the lack of S6K1-mediated negative feedback decreased insulin receptor substrate-1 (IRS-1) serine phosphorylation, resulting in activation of survival pathways mediated by phosphatidylinositol 3-kinase/Akt and extracellular signal-regulated kinase (ERK). However, S6K1−/− hepatocytes underwent apoptosis on serum withdrawal in combination with phosphatidylinositol 3-kinase (PI3K) or ERK inhibitors. Conclusion: This finding might explain the mechanism of resistance to mTOR inhibitors in cancer treatments and strongly suggests that the inhibition of S6K1 could protect against acute liver failure and, in combination with inhibitors that abrogate the sustained activation of Akt and ERK, could improve the efficacy of hepatocarcinoma (HCC) treatment. (Hepatology 2009.)
Fluid flow and heat transfer characteristics of cone orifice jet (effects of cone angle)
Authors: Kito Mizuki , Shakouchi Toshihiko , Tsujimoto Koichi , Ando Toshitake 
Published: February 2009

AbstractThe use of a jet from an orifice nozzle with a saddle‐backed‐shape velocity profile and a contracted flow at the nozzle exit may improve the heat transfer characteristics on an impingement plate because of its larger centerline velocity. However, it requires more power to operate than a common nozzle because of its higher flow resistance. We therefore initially considered the use of a cone orifice nozzle to obtain better heat transfer performance as well as to decrease the flow resistance. We examined the effects of the cone angle α on the cone orifice free jet flow and heat transfer characteristics of the impinging jet. We compared two nozzles: a pipe nozzle and a quadrant nozzle. The first one provides a velocity profile of a fully developed turbulent pipe flow, and the second has a uniform velocity profile at the nozzle exit. We observed a significant enhancement of the heat transfer characteristics of the cone orifice jets at Re=1.5×104. Using the cone orifice impinging jets enhanced the heat transfer rates as compared to the quadrant jet, even when the jets were supplied with the same operational power as the pipe jet. For instance, a maximum enhancement up to approximately 22% at r/do≅0.5 is observed for α=15°. In addition, an increase of approximately 7% is attained as compared to when the pipe jet was used. © 2009 Wiley Periodicals, Inc. Heat Trans Asian Res; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/htj.20243
Vortex structure behind highly heated two cylinders in parallel arrangements
Authors: Kurita Eiichirou , Yahagi Yuji 
Published: February 2009

AbstractVortex structures behind twin, highly heated cylinders in parallel arrangements have been investigated experimentally. The experiments were conducted under the following conditions: cylinder diameter, D=4mm; mean flow velocity, U∞ = 1.0 m/s; Reynolds number, Re=250; cylinder clearance, S/D=0.5 to 1.4; and cylinder heat flux, q=0 to 72.6kW/m2. For S/D>1.2, the Karman vortex street is formed alternately behind each cylinder divided on the slit flow. The slit flow velocity increases with a decrease in S/D and decreases with increasing heat flux. For S/D < 1.2, the wake vortexes become asymmetric having small and large scale vortexes divided by the slit flow. In the small scale vortexes, the symmetric counter‐rotating twin vortexes are formed just behind the cylinders. In the large scale vortexes, the generated vortexes have a similar structure to a Karman vortex even though the Strouhal number is approximately half of the ordinary single cylinder vortex. For isothermal conditions, the transition phenomena from symmetric to asymmetric wake structures are observed in the range of 0.9 < S/D <1.2. In addition, the asymmetric vortexes are irregularly switched up and down in the case of isothermal conditions. In the highly heated condition, the switching phenomena and the transition phenomena could not be observed and the small scale vortexes always formed behind the upper cylinder. The critical S/D increases approximately 30% in the heated condition (q=72.6kW/m2). As a result, the increased local kinematic viscosity and S/D play a key role for the vortex structure and formation behind arrangements of two parallel cylinders. © 2009 Wiley Periodicals, Inc. Heat Trans Asian Res; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/htj.20244
Season of diagnosis has no effect on survival from malignant melanoma
Authors: Jayasekara Harindra , Karahalios Emily , Thursfield Vicky , Giles Graham G. , English Dallas R. 
Published: February 2009

AbstractDiagnosis in summer had been shown to be associated with better survival from some cancers, but such studies on malignant melanoma where sun exposure is a risk factor for disease are rare. We evaluated seasonality in melanoma diagnosis and its effect on survival in Victoria, Australia using 26,060 cases reported to the population‐based Victorian Cancer Registry during 1986–2004. To estimate the amplitude of the seasonal variation, we calculated the ratio of the number of melanoma cases diagnosed in summer to that in winter. Linear regression was undertaken to assess the variation in thickness, the main prognostic indicator for melanoma, by season of diagnosis adjusting for sex, anatomical site, year of diagnosis and age at diagnosis. We modeled excess mortality using Poisson regression controlling for possible confounders in order to study the effect of season of diagnosis on survival. An overall 46% summer diagnostic excess was evident (summer‐to‐winter ratio 1.46; 95% CI 1.41, 1.52). Results of linear regression showed that melanoma diagnosed in winter were thicker than those diagnosed in any other season (percentage difference in thickness −2.01, −6.97 and −10.68 for spring, summer and autumn, respectively; p < 0.001). In the Poisson regression model of relative survival, cases diagnosed in spring, summer or autumn had slightly lower excess mortality than those diagnosed in winter before adjustment for other variables, but after adjustment the excess mortality ratios were close to unity. Our findings do not support the hypothesis that melanoma cases diagnosed in winter have worse prognosis than cases diagnosed in other seasons. © 2009 UICC
Functional analysis of the ‐2548G/A leptin gene polymorphism in breast cancer cells
Authors: Terrasi Marianna , Fiorio Elena , Mercanti Anna , Koda Mariusz , Moncada Camilo A. , Sulkowski Stanislaw , Merali Salim , Russo Antonio , Surmacz Eva 
Published: February 2009

AbstractLeptin is overexpressed in human breast tumors and is produced by breast cancer cells in response to obesity‐related stimuli. The leptin promoter polymorphism Lep‐2548G/A can be associated with increased leptin secretion by adipocytes and elevated cancer risk. However, molecular mechanisms underlying the link between Lep‐2548G/A and breast cancer have never been addressed. Lep‐2548G/A is proximal to a binding site for the transcriptional factor Sp1. Furthermore nucleolin, a transcriptional repressor, can bind Sp1 or its consensus site. Consequently, we focused on the impact of Lep‐2548G/A on Sp1‐ and nucleolin‐dependent leptin transcription in breast cancer cells. The Lep‐2548G/A was identified in a homozygous conformation in BT‐474 and SK‐BR‐3 breast cancer cells, in a heterozygous conformation in MDA‐MB‐231 cells, and a wild‐type Lep‐2548G/G sequence was present in MCF‐7 and ZR‐75‐1 cells. The occurrence of Lep‐2548A/A and Lep‐2548G/A coincided with high and intermediate leptin mRNA expression, respectively, while cells containing Lep‐2548G/G expressed low leptin mRNA levels. We demonstrated that the existence of Lep‐2548G/A improved efficient recruitment of Sp1 to DNA under insulin treatment, while Sp1 loading on DNA containing Lep‐2548G/G was not insulin‐dependent. In contrast, nucleolin binding to Lep‐2548G/A was downregulated in response to insulin, while it was not regulated on Lep‐2548G/G. The presence of Lep‐2548G/A was studied in breast cancer epithelial cells by IHC and LCM. Interestingly, all 14 tumors expressing high leptin levels contained Lep‐2548A/A. In conclusion, the occurrence of Lep‐2548G/A can enhance leptin expression in breast cancer cells via Sp1‐ and nucleolin‐dependent mechanisms and possibly contribute to intratumoral leptin overexpression. © 2009 UICC
Essential role of Notch signaling in apoptosis of human pancreatic tumoral cells mediated by exosomal nanoparticles
Authors: Ristorcelli Elodie , Beraud Evelyne , Mathieu Sylvie , Lombardo Dominique , Verine Alain 
Published: February 2009

AbstractWe previously reported that exosomal nanoparticles secreted by human pancreatic tumoral cell lines decrease tumoral cell proliferation through the mitochondria‐dependent apoptotic pathway, because of activation of pro‐apoptotic phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and of glucose synthase kinase‐3β (GSK‐3β). Interactions between exosomal nanoparticles and cells are thought to involve membrane lipid rafts. However, the underlying mechanism is unknown. Here, we report that the interaction of exosomal nanoparticles with pancreatic cancer cells led to decreased expression of hairy and enhancer‐of‐split homolog‐1 (Hes‐1), the intranuclear target of Notch‐1 signaling pathway, and to activation of the apoptotic pathway after a cell cycle arrest in G0G1 phase. Strikingly, the expression level of Notch‐1 pathway components was critical, because exosomal nanoparticles decreased the proliferation of cells in which these partners are either weakly represented, in differentiated adenocarcinoma cells, or inhibited, in poorly differentiated carcinoma cells, by blocking presenilin in the γ‐secretase complex that regulates the Notch‐1 pathway. Overexpression of Notch‐1 intracellular domain resulted in the reversion of the cell proliferation inhibition promoted by exosomal nanoparticles. Blocking presenilin unexpectedly resulted in activation of PTEN and GSK‐3β. Conversely, inhibiting either PTEN or GSK‐3β increased Hes‐1 expression and partially counteracted the inhibition of proliferation promoted by exosomal nanoparticles, highlighting reciprocal regulations between Notch signaling and PTEN/GSK‐3β. We concluded that interactions of exosomal nanoparticles with target cells, at lipid rafts where Notch‐1 pathway partners are localized, hampered the functioning of the Notch‐1 survival pathway and activated the apoptotic pathway, which determines tumoral cell fate. © 2009 UICC
Stromal MCP‐1 in mammary tumors induces tumor‐associated macrophage infiltration and contributes to tumor progression
Authors: Fujimoto Hiroshi , Sangai Takafumi , Ishii Genichiro , Ikehara Akashi , Nagashima Takeshi , Miyazaki Masaru , Ochiai Atsushi 
Published: February 2009

AbstractThere is growing evidence that tumor‐associated macrophages (TAMs) promote tumor growth and dissemination. Many individual reports have focused on the protumor function of molecules linked to the recruitment of macrophages, but little is known about which factor has the strongest impact on recruitment of macrophages in breast cancer. To elucidate this question, we performed RT‐PCR using species‐specific primers and evaluated tumoral and stromal mRNA expression of macrophage chemoattractants separately in human breast tumor xenografts. The correlation between the tumoral or stromal chemoattractant mRNA expression including monocyte chemoattractant protein‐1 (MCP‐1) (CCL2), MIP‐1α (CCL3), RANTES (CCL5), colony‐stimulating factor 1, tumor necrosis factor α, platelet‐derived growth factor (PDGF)‐BB and macrophage infiltration were compared. There was significant positive correlation between stromal MCP‐1 expression and macrophage number (r = 0.63), and negative correlation between tumoral RANTES expression and macrophage number (r = −0.75). However, no significant correlation was found for the other tumoral and stromal factors. The interaction between the tumor cells and macrophages was also investigated. Tumor cell–macrophage interactions augmented macrophage‐derived MCP‐1 mRNA expression and macrophage chemotactic activity in vitro. Treatment of immunodeficient mice bearing human breast cancer cells with a neutralizing antibody to MCP‐1 resulted in significant decrease of macrophage infiltration, angiogenetic activity and tumor growth. Furthermore, immunohistochemical analysis of human breast cancer tissue showed stromal MCP‐1 had a significant correlation with relapse free survival (p = 0.029), but tumoral MCP‐1 did not (p = 0.105). These findings indicate that stromal MCP‐1 produced as a result of tumor–stromal interactions may be important for the progression of human breast cancer and macrophages may play an important role in this tumor–stroma interaction. © 2009 UICC.
Conducting suicide research in naturalistic clinical settings
Authors: Jobes David A. , Bryan Craig J. , Neal‐Walden Tracy A. 
Published: February 2009

AbstractUnique challenges arise for clinical researchers designing studies focused on suicidal behaviors due to the inherently high‐risk nature of such research. Traditional approaches to clinical trial design are briefly discussed, highlighting the limitations and obstacles of these approaches when working with suicidal individuals. Using their own personal experiences and setbacks from an ongoing clinical suicidology research program, the authors argue for greater emphasis on effectiveness and translational research designs conducted in naturalistic clinical settings to test the practical utility of empirically‐supported treatments for suicidal behaviors, to gain new perspectives on suicidal individuals, and to better understand the nature of suicidal risk. © 2009 Wiley Periodicals, Inc. J Clin Psychol 65:1–14, 2009.
Discharge variability for an artesian spring of the Edwards Aquifer: Comal Springs (1933–2007)
Authors: Cox Walter D. , Meng Lei , Khedun C. Prakash , Nordfelt Anna , Quiring Steven M. 
Published: February 2009

AbstractDaily discharge volumes of Comal Springs, the largest artesian spring of the Edwards Aquifer (EA) in Central Texas, were utilized to characterize the flow of Comal Springs for the period of record spanning 1933–2007. The influence of water extraction (pumping) on discharge characteristics during the record was examined and found to be statistically significant for both volume and variability of spring discharge (p < 0.01). Pumping explains approximately a quarter of the variation in annual discharge (r2 = 0.25) and nearly a third of the daily variability (r2 = 0.32) within the Comal Springs discharge record.Statistically significant teleconnections to flow are demonstrated within the discharge record of Comal Springs. The El Niño‐Southern Oscillation (ENSO, as measured by the Southern Oscillation Index) and the Pacific Decadal Oscillation (PDO) are shown to exhibit statistically significant correlations with annual mean flow from Comal Springs. PDO modulation of ENSO results in mean flow anomalies of 21.9% between extreme quintile years. The Atlantic Multi‐decadal Oscillation (AMO) appears to exert influence based on the magnitude of the index value, irrespective of its positive or negative condition (p < 0.01), with the highest quintile (based on magnitude) years correlating with strong positive flow anomalies. A composite index was developed which combines the AMO, PDO and SOI. The extreme quintile years of this index demonstrate a 32.4% divergence in flow (p < 0.01) while demonstrating a stronger skill at capturing negative flow anomalies than positive anomalies.Precipitation data, at 4‐km spatial resolution, were utilized to examine the temporal and spatial correlation of water input to the EA with rates of average monthly discharge from Comal Springs. The spatial dependence of the correlation between precipitation and Comal Springs discharge indicates significant seasonal variability. Overall, the correlation between precipitation and discharge is significant for spring, summer and fall seasons and not significant for winter. Copyright © 2009 Royal Meteorological Society
Analysis of anaesthetics and analgesics in human urine by headspace SPME and GC
Authors: Raikos Nikolaos , Theodoridis Georgios , Alexiadou Efi , Gika Helen , Argiriadou Helena , Parlapani Heleni , Tsoukali Heleni 
Published: February 2009

AbstractThe determination of widely used anaesthetic and analgesic drugs in biological fluids is of major clinical importance. Typical methods used for sample preparation employ liquid–liquid extraction protocols which are complex, costly, not handy and not amenable to automation. In the present communication, we report the development of a methodology that employs headspace solid‐phase microextraction (HS‐SPME) for the determination of four anaesthetic (lidocaine, midazolam, diazepam and ketamine) and three analgesic drugs (fentanyl, remifentanyl and codeine) in human urine. Important parameters controlling SPME were studied: selection of SPME fibre, type and amount of salt added, preheating and extraction time, extraction temperature, sample volume and desorption time. GC with nitrogen phosphorus detection (GC‐NPD) facilitates sensitive and selective detection of the anaesthetics. The developed method renders an efficient tool for the precise and sensitive determination of the anaesthetics and analgesics in human urine (RSDs ranged from 7.7 to 12.6%, whereas LODs ranged from 0.01 to 1.5 ng/mL). The method was applied to the determination of the anaesthetics and analgesics in human urine from patients that had undergone coronary by‐pass surgery operations. The proposed protocol can function as an attractive alternative for clinical acute intoxications and medico‐legal cases.