bluuebunny/crossref_metadata_2025 huggingface dataset:
Blinded by the Light: Molecular Imaging in Pancreatic Adenocarcinoma
Authors: Collisson Eric , Tempero Margaret
Published: November 2010

The early detection and optimal perisurgical management of pancreatic adenocarcinoma are paramount goals in our quest to increase cure rates in this lethal malignancy. Molecular imaging techniques may be the conduit through which new genomic and proteomic discoveries about this disease are brought to the clinic. Clin Cancer Res; 17(2); 203–5. ©2010 AACR.
Low versus High Gas Flow Rate for Respiratory Support of Infants at Birth: A Manikin Study
Authors: te Pas Arjan B. , Schilleman Kim , Klein Mirjam , Witlox Ruben S. , Morley Colin J. , Walther Frans J.
Published: November 2010

Background: Neonatal resuscitation guidelines do not specify the gas flow rate during mask ventilation. Aim: Investigating the effect of gas flow rates on pressures, volumes delivered and mask leak. Methods: Flow 5 and 10 liters/min were tested. In study part 1, pressure ranges were measured when ventilating an intubated manikin with a Neopuff®. In study part 2, pediatric staff mask-ventilated a manikin (peak inflation pressure (PIP) 30 cm H2O, positive end expiratory pressure (PEEP) 5 cm H2O). We measured pressures, expired tidal volume (VTe) and mask leak. Results: Study part 1:an intubated manikin was ventilated with flow 5 versus 10 liters/min: range in PEEP was 0.4–3.6 and 2–14 cm H2O, respectively, maximum PIP was 73 cm H2O with both flow rates. Study part 2: when mask ventilation was given with flow 5 versus 10 liters/min: leak decreased (24% (8–85) vs. 80% (34– 94); p < 0.0001), VTe increased (6.7 (5.1–7.8) vs. 4.7 (2.4–7.0) ml; p < 0.001), PEEP decreased (3.1 (0.8) vs. 3.7 (0.7) cm H2O; p < 0.001), PIP was similar (28.1 (2.7) vs. 28.0 (2.3) cm H2O; NS). Large leaks decreased VTe and PEEP during both flow rates, PIP only with flow 5 liters/min. Conclusion: A low flow rate during neonatal mask ventilation may be a good alternative approach in reducing mask leak, provided that inflation time and flow rate warrants set pressures. Only large leaks seem to influence delivered pressures and volumes. Before resuscitation guidelines are advised, more studies on gas flow rates are needed.
Meconium Aspiration Delays Normal Decline of Pulmonary Vascular Resistance Shortly after Birth through Lung Parenchymal Injury
Authors: Ban Ryoichi , Ogihara Tohru , Mori Yasuhiko , Oue Shinya , Ogawa Satoru , Tamai Hiroshi
Published: November 2010

Background: Persistent pulmonary hypertension of the newborn is often associated with meconium aspiration syndrome (MAS) or perinatal asphyxia. Objective: To determine the effect of meconium or asphyxia on pulmonary arterial pressure and circulating levels of vasoactive substances, we conducted a prospective study of 54 term infants, including infants with meconium-stained amniotic fluid with normal (MSAF) or abnormal (MAS) chest X-ray findings, infants with perinatal asphyxia, and controls. The purpose of this study was to determine the group most likely to have elevated pulmonary arterial pressure and a disturbed balance between vasoactive substances. Methods: To estimate the pulmonary arterial pressure by echocardiography, we used the ratio of the right to left systolic ventricular pressure (RVP/LVP ratio). We measured the plasma concentrations of endothelin-1 (ET-1), cyclic guanosine monophosphate (cGMP) as an indicator of nitric oxide (NO) production, and 6-keto-prostaglandin F1α (6-keto-PGF1α) for the estimation of prostacyclin concentration. We also measured KL-6 as a marker of lung injury. Results:The RVP/LVP ratio was significantly higher in the MAS group than the other groups on day 0. Although ET-1 and 6-keto-PGF1α levels were comparable among all groups, the cGMP level on days 3–5 and the KL-6 level throughout the first postnatal week were significantly higher in the MAS group. Conclusions: It is possible that meconium aspiration delays normal decline of pulmonary vascular resistance shortly after birth through lung parenchymal injury. The subsequent increase of cGMP in MAS may be an adaptive response to prevent further elevation of pulmonary arterial pressure by inducing NO.
Respiratory Viruses, Eosinophilia and Their Roles in Childhood Asthma
Authors: Callaway Zak , Kim Chang-Keun
Published: November 2010

With the advent of highly sensitive and specific screening of respiratory specimens for viruses, new viruses are discovered, adding to the growing list of those associated with wheezing illness and asthma exacerbations. It is not known whether early childhood infections with these viruses cause asthma, and, if so, what exactly are the pathophysiologic mechanisms behind its development. The current consensus is that respiratory viral infection works together with allergy to produce the immune and physiologic conditions necessary for asthma diasthesis. One link between viruses and asthma may be the eosinophil, a cell that plays a prominent role in asthma and allergy, but can also be found in the body in response to viral infection. In turn, the eosinophil and its associated products may be novel therapeutic targets, or at the very least, used to elucidate the complex pathophysiologic pathways of asthma and other respiratory illnesses. Together or separately, they can be used for diagnosis, treatment and monitoring. Not only symptoms, but also the underlying disease mechanisms must be taken into consideration for the optimal care of a patient.
Association Study of Gene Polymorphisms Involved in Vascular Alterations in Elderly Hypertensives with Subjective Memory Complaints
Authors: Watfa Ghassan , Marteau Jean Brice , Rossignol Patrick , Kearney-Schwartz Anna , Fay Renaud , Bracard Serge , Felblinger Jacques , Boivin Jean-Marc , Lacolley Patrick , Visvikis-Siest Sophie , Benetos Athanase , Zannad Faïez
Published: November 2010

Background: We have recently shown that vascular abnormalities are associated with cognitive impairment as well as with white matter hyperintensities (WMH) in elderly hypertensive patients presenting with subjective memory complaints (SMC), a population at high risk of developing dementia. The aim of the present study was to identify genetic variants associated with the degree of cognitive impairment and the severity of WMH in the same study population, focusing on genes involved in vascular alterations. Methods: 50 gene polymorphisms known to be associated with vascular alterations (blood pressure regulation, lipid and homocysteine metabolism, thrombosis and inflammation) were genotyped using a multilocus genotyping assay in 369 elderly treated hypertensive patients >60 years of age and presenting with SMC but no dementia. The patients underwent a combination of neuropsychological tests and brain magnetic resonance imaging with semiquantification of WMH. Results: None of the tested polymorphisms were found to be associated with age- and gender-adjusted memory score, visual capacity, body-mass-index-adjusted verbal fluency score or the age-adjusted WMH Fazekas score. Conclusion: Our results suggest that the associations between arterial factors and cognitive decline or WMH are not genetically driven by the genes we investigated, at least at this early stage of cognitive decline.
Adenosine Derived From ADP Can Contribute to Inhibition of Platelet Aggregation in the Presence of a P2Y
12
Antagonist
Authors: Iyú David , Glenn Jackie R. , White Ann E. , Fox Sue C. , Heptinstall Stan
Published: November 2010

Objective—

To investigate whether adenosine diphosphate (ADP)–derived adenosine might inhibit platelet aggregation, especially in the presence of a P2Y
12
antagonist, where the effects of ADP at the P2Y
12
receptor would be prevented.

Methods and Results—

Platelet aggregation was measured in response to thrombin receptor activator peptide by platelet counting in platelet-rich plasma (PRP) and whole blood in the presence of ADP and the P2Y
12
antagonists cangrelor, prasugrel active metabolite, and ticagrelor. In the presence of a P2Y
12
antagonist, preincubation of PRP with ADP inhibited aggregation; this effect was abolished by adenosine deaminase. No inhibition of aggregation occurred in whole blood except when dipyridamole was added to inhibit adenosine uptake into erythrocytes. The effects of ADP in PRP and whole blood were replicated using adenosine and were directly related to changes in cAMP (assessed by vasodilator-stimulated phosphoprotein phosphorylation). All results were the same irrespective of the P2Y
12
antagonist used.

Conclusion—

ADP inhibits platelet aggregation in the presence of a P2Y
12
antagonist through conversion to adenosine. Inhibition occurs in PRP but not in whole blood except when adenosine uptake is inhibited. None of the P2Y
12
antagonists studied replicated the effects of dipyridamole in the experiments that were performed.
Telomerase Activation in Atherosclerosis and Induction of Telomerase Reverse Transcriptase Expression by Inflammatory Stimuli in Macrophages
Authors: Gizard Florence , Heywood Elizabeth B. , Findeisen Hannes M. , Zhao Yue , Jones Karrie L. , Cudejko Céline , Post Ginell R. , Staels Bart , Bruemmer Dennis
Published: November 2010

Objective—

Telomerase serves as a critical regulator of tissue renewal. Although telomerase activity is inducible in response to various environmental cues, it remains unknown whether telomerase is activated during the inflammatory remodeling underlying atherosclerosis formation. To address this question, we investigated in the present study the regulation of telomerase in macrophages and during atherosclerosis development in low-density lipoprotein receptor–deficient mice.

Methods and Results—

We demonstrate that inflammatory stimuli activate telomerase in macrophages by inducing the expression of the catalytic subunit telomerase reverse transcriptase (TERT). Reporter and chromatin immunoprecipitation assays identified a previously unrecognized nuclear factor-κB (NF-κB) response element in the TERT promoter, to which NF-κB is recruited during inflammation. Inhibition of NF-κB signaling completely abolished the induction of TERT expression, characterizing TERT as a bona fide NF-κB target gene. Furthermore, functional experiments revealed that TERT deficiency results in a senescent cell phenotype. Finally, we demonstrate high levels of TERT expression in macrophages of human atherosclerotic lesions and establish that telomerase is activated during atherosclerosis development in low-density lipoprotein receptor–deficient mice.

Conclusion—

These results characterize TERT as a previously unrecognized NF-κB target gene in macrophages and demonstrate that telomerase is activated during atherosclerosis. This induction of TERT expression prevents macrophage senescence and may have important implications for the development of atherosclerosis.
Critical Roles of Macrophages in the Formation of Intracranial Aneurysm
Authors: Kanematsu Yasuhisa , Kanematsu Miyuki , Kurihara Chie , Tada Yoshiteru , Tsou Tsung-Ling , van Rooijen Nico , Lawton Michael T. , Young William L. , Liang Elena I. , Nuki Yoshitsugu , Hashimoto Tomoki
Published: November 2010

Background and Purpose—

Abnormal vascular remodeling triggered by hemodynamic stresses and inflammation is believed to be a key process in the pathophysiology of intracranial aneurysms. Numerous studies have shown infiltration of inflammatory cells, especially macrophages, into intracranial aneurysmal walls in humans. Using a mouse model of intracranial aneurysms, we tested whether macrophages play critical roles in the formation of intracranial aneurysms.

Methods—

Intracranial aneurysms were induced in adult male mice using a combination of a single injection of elastase into the cerebrospinal fluid and angiotensin II-induced hypertension. Aneurysm formation was assessed 3 weeks later. Roles of macrophages were assessed using clodronate liposome-induced macrophage depletion. In addition, the incidence of aneurysms was assessed in mice lacking monocyte chemotactic protein-1 (CCL2) and mice lacking matrix metalloproteinase-12 (macrophage elastase).

Results—

Intracranial aneurysms in this model showed leukocyte infiltration into the aneurysmal wall, the majority of the leukocytes being macrophages. Mice with macrophage depletion had a significantly reduced incidence of aneurysms compared with control mice (1 of 10 versus 6 of 10;
P
<0.05). Similarly, there was a reduced incidence of aneurysms in mice lacking monocyte chemotactic protein-1 compared with the incidence of aneurysms in wild-type mice (2 of 10 versus 14 of 20,
P
<0.05). There was no difference in the incidence of aneurysms between mice lacking matrix metalloproteinase-12 and wild-type mice.

Conclusions—

These data suggest critical roles of macrophages and proper macrophage functions in the formation of intracranial aneurysms in this model.
Intracranial Large Vessel Occlusion as a Predictor of Decline in Functional Status After Transient Ischemic Attack
Authors: Poisson Sharon N. , Nguyen-Huynh Mai N. , Johnston S. Claiborne , Furie Karen L. , Lev Michael H. , Smith Wade S.
Published: November 2010

Background and Purpose—

Clinical scores help predict outcome after transient ischemic attack (TIA), and imaging studies may improve the accuracy of predictions. Intracranial large vessel occlusion (LVO) predicts poor outcome after stroke, but the natural history of symptomatic intracranial LVO in patients with TIA is unknown.

Methods—

We studied patients presenting with TIA in the STOP Stroke Study, a prospective imaging-based study of stroke outcomes. All patients underwent brain CTA. If an intracranial vascular occlusion was found in an appropriate territory to account for clinical findings, then it was judged to be a symptomatic LVO. Baseline characteristics, follow-up events, and outcomes were collected. Characteristics of patients with and without LVO were compared using χ
2
and
t
tests. Predictors of LVO were analyzed by univariate and multivariate analysis. LVO was assessed as a predictor of asymptomatic outcome (modified Rankin scale [mRS] score, 0), poor outcome (mRS score ≤3), and increase in mRS score over the study period.

Results—

Of 97 patients with TIA, 13 (13%) had symptomatic intracranial LVO. Patients with LVO had higher baseline NIHSS on emergency department arrival, which was an independent predictor of LVO (OR, 1.15 per point; 95% CI, 1.02–1.29;
P
=0.02). Patients with LVO were more likely to have an increase in mRS score during the 90-day follow-up (
P
=0.03). LVO independently predicted an increase in mRS score (OR, 4.76; 95% CI, 1.23–18.43;
P
=0.02) and was a borderline predictor of poor outcome (mRS score ≥3; OR, 5.07; 95% CI, 0.92–28.03;
P
=0.06).

Conclusions—

LVO is found in >1 in 10 patients presenting with TIA and predicts a decline in functional status, likely attributable to new brain ischemia.
Myeloid-Specific Deletion of the Mineralocorticoid Receptor Reduces Infarct Volume and Alters Inflammation During Cerebral Ischemia
Authors: Frieler Ryan A. , Meng He , Duan Sheng Zhong , Berger Stefan , Schütz Günther , He Yangdong , Xi Guohua , Wang Michael M. , Mortensen Richard M.
Published: November 2010

Background and Purpose—

Mineralocorticoid receptor (MR) antagonists have protective effects in rodent models of ischemic stroke, but the cell type-specific actions of these drugs are unknown. In the present study, we examined the contribution of myeloid cell MR during focal cerebral ischemia using myeloid-specific MR knockout mice.

Methods—

Myeloid-specific MR knockout mice were subjected to transient (90 minutes) middle cerebral artery occlusion followed by 24 hours reperfusion (n=5 to 7 per group). Ischemic cerebral infarcts were identified by hematoxylin and eosin staining and quantified with image analysis software. Immunohistochemical localization of microglia and macrophages was performed using Iba1 staining, and the expression of inflammatory markers was measured after 24 hours of reperfusion by quantitative reverse transcription–polymerase chain reaction.

Results—

Myeloid-specific MR knockout resulted in a 65% reduction in infarct volume (
P
=0.005) after middle cerebral artery occlusion. This was accompanied by a significant reduction in activated microglia and macrophages in the ischemic core. Furthermore, myeloid-specific MR knockout suppressed classically activated M1 macrophage markers tumor necrosis factor-α, interleukin-1β, monocyte chemoattractant protein-1, macrophage inflammatory protein-1α, and interleukin-6 at the same time as partially preserving the induction of alternatively activated, M2, markers Arg1, and Ym1.

Conclusions—

These data demonstrate that myeloid MR activation exacerbates stroke and identify myeloid MR as a critical target for MR antagonists. Furthermore, these data indicate that MR activation has an important role in controlling immune cell function during the inflammatory response to stroke.
Is Levinas’s Philosophy a Response to the Holocaust?
Authors: Shaw Joshua
Published: November 2010

Some commentators have claimed that Emmanuel Levinas’s philosophy should be understood as a response to the Holocaust. This study assesses that claim. It begins by clarifying what it means to call his philosophy a “response.” The bulk of the article then analyzes his essay, “Useless Suffering,” one of the few works in Levinas’s philosophic oeuvre where he discusses the Holocaust. Levinas is widely read as claiming that there can be no explanation for the Holocaust—that it marks “the end of theodicy.” It is shown, however, that his point is not that it cannot be explained, but that we misjudge the nature of evil when we view it as calling for explanation rather than practical activity. Based on this analysis, it is argued that Levinas’s philosophy can be understood as a response to the Holocaust in the sense of being a performative writing that sought to address the evil that occurred in the Holocaust by transforming the ethical sensibilities of his readers.
The Scope of the Medical Duty to Treat: An Analytical Study under Jordanian Law and Common Law
Authors: Masadeh Aymen Khaled
Published: November 2010

Under common law, a physician may not have a duty to treat in the absence of a physician-patient contractual relationship. This is generally called the ‘no duty’ rule. This paper argues against the application of this rule to emergency cases. A number of recent cases have made remarkable development with regards to the ‘medical duty to treat’. Jordanian law imposes the ‘medical duty to treat’ in emergency cases and gives physicians the choice to accept or refuse to treat in non-emergency cases. Jordanian law allows physicians to discontinue treating their patients provided that no harm results from this abandonment and that patients are appropriately informed of how to continue their treatment. This paper argues against this legal approach in cases where a patient contracts with a physician to treat him personally. This paper concludes that physicians should be required, in all jurisdictions, to provide medical care in all emergency cases regardless of whether a physician-patient contract exists. It also submits that Jordanian law should not allow physicians to abandon their patients in cases where they are contractually required to provide medical care personally.
The Role of Religious Ritual in Social Capital Formation for Poverty Alleviation and Social Development. Theoretical and Methodological Points of Departure of a South African Exploration
Authors: Wepener Cas , Barnard Marcel , Swart Ignatius , ter Haar Gerrie
Published: November 2010

The article is a presentation of a South African research project in which researchers in the fields of ritual-liturgical studies and social development are collaborating to explore the role of religious ritual in the kinds of social capital formation that have a direct significance and implication for alleviating poverty and promoting social development at grassroots level. Focusing on Christian congregations in poor socio-economic contexts in the Western Cape and KwaZulu-Natal, the aim of the research is to understand social capital formation through the lens of religious ritual. The research project builds on the hypothesis that social capital has a role to play in the related goals of poverty alleviation and social development, something which it seeks to conceptualise and explore in greater detail. Within this framework the discussion explores and contextualises the conceptual link between social capital and the practice of religious ritual in present-day South African society by drawing on existing research and theoretical debates, both nationally and internationally. This enables the authors to present some additional notes on the key theoretical, conceptual and methodological points of departure of the undertaken project. These are followed by a number of concluding observations about the modes of investigation and action steps through which the research topic is currently being further developed.
Behavioural precursors and HIV testing behaviour among African American women
Authors: Uhrig Jennifer D , Davis Kevin C , Rupert Doug , Fraze Jami
Published: November 2010

Objective: To examine whether there is an association between knowledge, attitudes and beliefs, reported intentions to get an HIV test, and reported HIV testing behaviour at a later date among a sample of African American women.

Design: Secondary analysis of data collected from October 2007 through March 2008 for a randomized controlled experiment that was one part of a comprehensive evaluation of the ‘Take Charge. Take the Test’ HIV social marketing campaign.

Method: A series of logistic regression models were estimated to assess the effects of baseline knowledge and attitudes and beliefs on intention at two and six weeks post-baseline. Logistic regression models were also estimated to assess the effects of intention on HIV testing at both follow-ups.

Results: A statistically-significant association between baseline attitudes and beliefs and subsequent HIV testing intentions was found. Knowing where to get a free HIV test at baseline was also significantly associated with reported intentions at follow-up. Reported intentions were significantly associated with reported HIV testing at follow-up.

Conclusion: The study’s findings reiterate the importance of applying behaviour change theories and measuring behavioural precursors in the design and evaluation of HIV testing campaigns.
Dynamics of influence in international politics: The ICC, BIAs, and economic sanctions
Authors: Nooruddin Irfan , Payton Autumn Lockwood
Published: November 2010

In 2002, the USA asked all countries to sign agreements exempting US citizens from prosecution by the International Criminal Court (ICC) and threatened economic sanctions if they refused. Some countries yielded to this pressure even after ratifying the ICC Statute, while others chose to honor their original commitments. Why were some countries more responsive to US influence than others? This article provides an explanation of state vulnerability to attempts of influence through the lens of economic sanctions. Assessing the success of sanctions is difficult because of the selection bias in the instances of the use of such strategies observed by the researcher. Since all countries were asked to sign such agreements, one can observe exactly which signed, whether sanctions were enforced, and how quickly countries responded to such pressure. Arguments about sources of influence — shared interests, economic and security dependence, and domestic politics — are tested using an original dataset collected on country decisions to sign bilateral immunity agreements (BIAs). The authors find support for some existing explanations, including relative power and the relationship of dependency, while previously held beliefs about alliance and security relationships appear to be less influential on decisions to ratify BIAs. These findings have implications for existing research programs on economic sanctions, international organizations, and power politics.
Geography, poverty and conflict in Nepal
Authors: Do Quy-Toan , Iyer Lakshmi
Published: November 2010

We conduct an empirical analysis of the geographic, economic, and social factors that contributed to the spread of civil war in Nepal over the period 1996—2006. This within-country analysis complements existing cross-country studies on the same subject. Using a detailed dataset to track civil war casualties across space and over time, several patterns are documented. Conflict-related deaths are significantly higher in poorer districts and in geographical locations that favor insurgents, such as mountains and forests; a 10 percentage point increase in poverty is associated with 25—27 additional conflict-related deaths. This result is similar to that documented in cross-country studies. In addition, the relationship with poverty and geography is similar for deaths caused by the insurgents and deaths caused by the state. Furthermore, poorer districts are likely to be drawn into the insurgency earlier, consistent with the theory that a lower cost of recruiting rebels is an important factor in starting conflict. On the other hand, geographic factors are not significantly associated with such onset, suggesting that they instead contribute to the intensity of violence only after conflict has started. Finally, in contrast to some cross-country analyses, ethnic and caste polarization, land inequality, and political participation are not significantly associated with violence.
As Pleasure Unfolds
Authors: Hofmann Wilhelm , van Koningsbruggen Guido M. , Stroebe Wolfgang , Ramanathan Suresh , Aarts Henk
Published: November 2010

Why do chronic dieters often violate their dieting goals? One possibility is that they experience stronger hedonic responses to tempting food than normal eaters do. We scrutinized hedonic processing in dieters and normal eaters (a) by manipulating food preexposure and (b) by assessing both immediate and delayed hedonic responses to tempting food with an adapted affect-misattribution procedure. Without food preexposure, dieters showed less positive hedonic responses than normal eaters (Study 1). When preexposed to tempting-food stimuli, however, dieters exhibited more positive delayed hedonic responses than normal eaters (Studies 1 and 2). Furthermore, delayed hedonic responding was meaningfully related to self-reported power of food and state cravings (Study 2). These findings suggest that dieters experience difficulties in down-regulating hedonic affect when in a “hot” state and that self-regulation research may benefit from a greater emphasis on temporal dynamics rather than static differences.
Stimulating Perspective and Reflection in a Course on Value-based Management
Authors: Harung Harald S.
Published: November 2010

Globalization, accelerating change, increasing complexity, interdisciplinary technologies, sustainability and the need for enhanced ethical behaviour—all call for more reflection and overview. The management course for technology students outlined in this article aims at increasing student’s independent thinking and perspective in three ways: (i) value-based management where sound human values are given higher priority than profit, (ii) parallels that link the natural sciences and the social sciences and (iii) knowledge from both East and West. Interdisciplinary parallels—which only takes a few minutes of each lesson—can be applied to any discipline and may improve the learner’s ability to think independently and to see interconnectedness.
Mitofusin 2 Inhibits Angiotensin II-Induced Myocardial Hypertrophy
Authors: Yu Haiyi , Guo Yanhong , Mi Lin , Wang Xueying , Li Lei , Gao Wei
Published: November 2010

Background and Objectives: Myocardial hypertrophy is a common clinical finding leading to heart failure and sudden death. Mitofusin 2 (Mfn2), a hyperplasia suppressor protein, is downregulated in hypertrophic heart. This study examined the role of Mfn2 in myocardial hypertrophy and its potential signal pathway. Methods and Results: In in vitro studies, neonatal cardiac myocytes were isolated and cultured. Incubation of cultured cardiomycytes with angiotensin II (Ang II) inhibited gene expression of Mfn2; induced cell hypertrophy and protein synthesis; and activated protein kinase Akt. Pretreatment of cells with AdMfn2—a replication-deficient adenoviral vector encoding rat Mfn2 gene—upregulated Mfn2 expression and subsequently attenuated Ang II-induced cell hypertrophy; protein synthesis; and Akt activation. In in vivo studies, direct gene delivery of AdMfn2 into myocardium decreased the infusion of Ang II-induced atrial natriuretic factor (ANF, a hypertrophic marker) expression and cardiomyocyte cross-sectional area. Consistently, upregulation of Mfn2 in myocardium decreased the thicknesses of anterior and posterior walls of left ventricle (LV) and the ratio of LV mass/body weight in Ang II-treated rats. Of note, AdGFP (control for AdMfn2) did not affect the effects of Ang II in vitro or in vivo. Conclusions: Upregulation of Mfn2 inhibits Ang II-induced myocardial hypertrophy. In this process, inhibition of Akt activation seems to play a significant role. These findings indicate Mfn2 is a critical protein in modulating myocyte hypertrophy.
Discrete and continuous scalar conservation laws
Authors: Abeyaratne Rohan , Knowles James K.
Published: November 2010

Motivated by issues arising for discrete second-order conservation laws and their continuum limits (applicable, for example, to one-dimensional nonlinear spring—mass systems), here we study the corresponding issues in the simpler setting of first-order conservation laws (applicable, for example, to the simplest theory of traffic flow). The discrete model studied here comprises a system of first-order nonlinear differential-difference equations; its continuum limit is a one-dimensional scalar conservation law. Our focus is on issues related to discontinuities — shock waves — in the continuous theory and the corresponding regions of rapid change in the discrete model. In the discrete case, we show that a family of new conservation laws can be deduced from the basic one, while in the continuous case we show that this is true only for smooth solutions. We also examine how well the continuous model approximates rapidly changing solutions of the discrete model, and this leads us to derive an improved continuous model which is of second-order. We also consider the form and implications of the second law of thermodynamics at shock waves in the scalar case.
Assessment of Airborne Total Volatile Organic Compounds of Niagara Falls Residences as Compared to Resident Lifestyle
Authors: Grenga Paolo N. , Gallagher Michael J. , McGahan Megan E. , Raymond Danielle M. , Priefer Ronny
Published: November 2010

An indoor air study was conducted during the summers of 2007 and 2008 to determine the effect(s) of resident lifestyle on the concentrations and distributions of volatile organic compounds (VOCs) in residences of the city of Niagara Falls, New York. A GrayWolf Sensing Solutions Total Volatile Organic Compound (TVOC) detector was used to measure TVOC concentrations and generic air readings of five predetermined locations within each of 58 residences. Factors including smoking, asthma, furnace filter condition, pest infestations and air conditioning and their effect(s) on TVOC concentrations were evaluated. The general distributions of TVOC within each residence were determined. Examining the latter three variables revealed no significant differences. However, TVOC concentrations increased as high as 20% in smoking households. Asthmatic households exhibited TVOC levels elevated as high as 33%. Additionally, TVOC levels from smoking households and asthmatic households gave a linear relationship (R2 =0.96).
The Hsp90 inhibitor IPI-504 overcomes bortezomib resistance in mantle cell lymphoma in vitro and in vivo by down-regulation of the prosurvival ER chaperone BiP/Grp78
Authors: Roué Gaël , Pérez-Galán Patricia , Mozos Ana , López-Guerra Mónica , Xargay-Torrent Sílvia , Rosich Laia , Saborit-Villarroya Ifigènia , Normant Emmanuel , Campo Elias , Colomer Dolors
Published: November 2010

Despite the promising introduction of the proteasome inhibitor bortezomib in the treatment of mantle cell lymphoma (MCL), not all patients respond, and resistance often appears after initial treatment. By analyzing a set of 18 MCL samples, including cell lines with constitutive or induced resistance to bortezomib, we found a high correlation between loss of sensitivity to the proteasome inhibitor and up-regulation of the prosurvival chaperone BiP/Grp78. BiP/Grp78 stabilization was ensured at a posttranscriptional level by an increase in the chaperoning activity of heat shock protein of 90 kDa (Hsp90). In bortezomib-resistant cells, both BiP/Grp78 knockdown and cell pretreatment with the Hsp90 inhibitor of the ansamycin class, IPI-504, led to synergistic induction of apoptotic cell death when combined with bortezomib. Cell exposure to the IPI-504–bortezomib combination provoked the dissociation of Hsp90/BiP complexes, leading to BiP/Grp78 depletion, inhibition of unfolded protein response, and promotion of NOXA-mediated mitochondrial depolarization. The IPI-504–bortezomib combination also prevented BiP/Grp78 accumulation, thereby promoting apoptosis and inhibiting the growth of bortezomib-resistant tumors in a mouse model of MCL xenotransplantation. These results suggest that targeting unfolded protein response activation by the inhibition of Hsp90 may be an attractive model for the design of a new bortezomib-based combination therapy for MCL.
A Markov decision analysis of allogeneic hematopoietic cell transplantation versus chemotherapy in patients with acute myeloid leukemia in first remission
Authors: Kurosawa Saiko , Yamaguchi Takuhiro , Miyawaki Shuichi , Uchida Naoyuki , Kanamori Heiwa , Usuki Kensuke , Yamashita Takuya , Watanabe Masato , Yakushiji Kazuaki , Yano Shingo , Nawa Yuichiro , Taguchi Jun , Takeuchi Jin , Tomiyama Junji , Nakamura Yuko , Miura Ikuo , Kanda Yoshinobu , Takaue Yoichi , Fukuda Takahiro
Published: November 2010

Various prospective trials have been performed to assess the roles of allogeneic hematopoietic cell transplantation (allo-HCT) and chemotherapy in patients with acute myeloid leukemia (AML) in first complete remission (CR1). However, the results have not always been consistent, and there has been a limited evaluation of quality of life (QOL) in these postremission strategies. We performed a Markov decision analysis that enabled us to compare survival outcomes with a QOL evaluation using a database of 2029 adult AML patients who achieved CR1. The Markov decision model compared 2 strategies: allo-HCT or chemotherapy in CR1. Patients who had intermediate- or unfavorable-risk AML had a longer life expectancy when they received allo-HCT in CR1 than patients treated with chemotherapy alone. Likewise, patients who had a suitable related donor who received allo-HCT in CR1 had a longer life expectancy. The life expectancy was shortened to a greater degree by adjustment for QOL in the allo-HCT group. Nevertheless, QOL-adjusted life expectancies in most of the subgroups remained longer in the allo-HCT group than in the chemotherapy group. Our results showed that older patients with a related donor and younger patients with unfavorable cytogenetics benefited the most from allo-HCT in CR1.
Combining two Meishan F2 crosses improves the detection of QTL on pig chromosomes 2, 4 and 6
Authors: Tortereau Flavie , Gilbert Hélène , Heuven Henri CM , Bidanel Jean-Pierre , Groenen Martien AM , Riquet Juliette
Published: November 2010

Background

In pig, a number of experiments have been set up to identify QTL and a multitude of chromosomal regions harbouring genes influencing traits of interest have been identified. However, the mapping resolution remains limited in most cases and the detected QTL are rather inaccurately located. Mapping accuracy can be improved by increasing the number of phenotyped and genotyped individuals and/or the number of informative markers. An alternative approach to overcome the limited power of individual studies is to combine data from two or more independent designs.

Methods

In the present study we report a combined analysis of two independent design (a French and a Dutch F2 experimental designs), with 2000 F2 individuals. The purpose was to further map QTL for growth and fatness on pig chromosomes 2, 4 and 6. Using QTL-map software, uni- and multiple-QTL detection analyses were applied separately on the two pedigrees and then on the combination of the two pedigrees.

Results

Joint analyses of the combined pedigree provided (1) greater significance of shared QTL, (2) exclusion of false suggestive QTL and (3) greater mapping precision for shared QTL.

Conclusions

Combining two Meishan x European breeds F2 pedigrees improved the mapping of QTL compared to analysing pedigrees separately. Our work was facilitated by the access to raw phenotypic data and DNA of animals from both pedigrees and the combination of the two designs with the addition of new markers allowed us to fine map QTL without phenotyping additional animals.
Robust patterns in the stochastic organization of filopodia
Authors: Husainy Asma N , Morrow Anne A , Perkins Theodore J , Lee Jonathan M
Published: November 2010

Background

Filopodia are actin-based cellular projections that have a critical role in initiating and sustaining directional migration in vertebrate cells. Filopodia are highly dynamic structures that show a rich diversity in appearance and behavior. While there are several mathematical models of filopodia initiation and growth, testing the capacity of these theoretical models in predicting empirical behavior has been hampered by a surprising shortage of quantitative data related to filopodia. Neither is it clear how quantitatively robust the cellular filopodial network is and how perturbations alter it.

Results

We have measured the length and interfilopodial separation distances of several thousand filopodia in the rodent cell line Rat2 and measured these parameters in response to genetic, chemical and physical perturbation. Our work shows that length and separation distance have a lognormal pattern distribution over their entire detection range (0.4 μm to 50 μm).

Conclusions

We find that the lognormal distribution of length and separation is robust and highly resistant to perturbation. We also find that length and separation are independent variables. Most importantly, our empirical data is not entirely in agreement with predictions made based on existing theoretical models and that filopodial size and separation are an order of magnitude larger than what existing models suggest.
Recovery from depressive symptoms, state anxiety and post-traumatic stress disorder in women exposed to physical and psychological, but not to psychological intimate partner violence alone: A longitudinal study
Authors: Blasco-Ros Concepción , Sánchez-Lorente Segunda , Martinez Manuela
Published: November 2010

Background

It is well established that intimate male partner violence (IPV) has a high impact on women's mental health. It is necessary to further investigate this impact longitudinally to assess the factors that contribute to its recovery or deterioration. The objective of this study was to assess the course of depressive, anxiety and post-traumatic stress disorder (PTSD) symptoms and suicidal behavior over a three-year follow-up in female victims of IPV.

Methods

Women (n = 91) who participated in our previous cross-sectional study, and who had been either physically/psychologically (n = 33) or psychologically abused (n = 23) by their male partners, were evaluated three years later. A nonabused control group of women (n = 35) was included for comparison. Information about mental health status and lifestyle variables was obtained through face-to-face structured interviews.

Results

Results of the follow-up study indicated that while women exposed to physical/psychological IPV recovered their mental health status with a significant decrease in depressive, anxiety and PTSD symptoms, no recovery occurred in women exposed to psychological IPV alone. The evolution of IPV was also different: while it continued across both time points in 65.21% of psychologically abused women, it continued in only 12.12% of physically/psychologically abused women while it was reduced to psychological IPV in 51.5%. Hierarchical multiple regression analyses indicated that cessation of physical IPV and perceived social support contributed to mental health recovery, while a high perception of lifetime events predicted the continuation of PTSD symptoms.

Conclusion

This study shows that the pattern of mental health recovery depends on the type of IPV that the women had been exposed to. While those experiencing physical/psychological IPV have a higher likelihood of undergoing a cessation or reduction of IPV over time and, therefore, could recover, women exposed to psychological IPV alone have a high probability of continued exposure to the same type of IPV with a low possibility of recovery. Thus, women exposed to psychological IPV alone need more help to escape from IPV and to recuperate their mental health. Longitudinal studies are needed to improve knowledge of factors promoting or impeding health recovery to guide the formulation of policy at individual, social and criminal justice levels.
Private and public health care in rural areas of Uganda
Authors: Konde-Lule Joseph , Gitta Sheba N , Lindfors Anne , Okuonzi Sam , Onama Virgil ON , Forsberg Birger C
Published: November 2010

Background

In many low and middle income countries, the private sector is increasingly becoming an important source of health care, filling gaps where no or little public health care is available. However, knowledge on the private sector providers is limited The objective of this study was to determine the type and number of different types of health care providers, and the quality, cost and utilization of care delivered by those providers in rural Uganda.

Methods

The study was carried out in three rural districts. Methods included (1) mapping of health care providers; (2) a household survey to determine morbidity and health care utilization; (3) a health facility survey to assess quality of care; (4) focus group discussions to get qualitative information on providers and provider choice; and (5) key informant interviews to further explore service characteristics.

Results

95.7% of all 445 facilities surveyed were private while 4.3% were public. Traditional practitioners and general merchandise shops that sold medicines comprised 77.1% of all providers. They had limited infrastructure and skills but were often located in the villages and therefore easily accessible. Among the formal providers there were 4 times as many private for profit providers than public, 76 versus 18. However, most of the private units were one-person drug shops.

In the household survey, 2580 persons were interviewed. 1097 (42%) had experienced illness during the preceding month. Care was sought in 54.1% of the cases. 35.6% were given self-treatment and in 10.3% no action was taken. Of the episodes for which people sought care at a health care facility, 37.0% visited a public health care provider, 39.7% a for profit provider, 11.8% a private not for profit provider, and 10.6% a traditional practitioner. Private for profit facilities were the most popular for ambulatory health care, while public facilities were preferred for more serious conditions and for hospitalization. Traditional practitioners were many but saw relatively few patients. They were mostly used for social problems and limited medical specific conditions.

Conclusions

Private providers play a major role in health care delivery in rural Uganda; reaching a wide client base. Traditional practitioners are many but have as much a social as a medical function in the community. The significance of the private health care sector points to the need to establish a policy that addresses quality and affordability issues and creates a strong regulatory environment for private practice in sub-Saharan Africa.
TOPBP1 missense variant Arg309Cys and breast cancer in a German hospital-based case-control study
Authors: Blaut Magda A , Bogdanova Natalia V , Bremer Michael , Karstens Johann H , Hillemanns Peter , Dörk Thilo
Published: November 2010

The DNA double strand break repair gene TOPBP1 has been suggested as a breast cancer susceptibility gene and a missense variant Arg309Cys was observed at elevated frequency in familial breast cancer cases compared to healthy controls from Finland. We found the Arg309Cys allele at a 13% carrier frequency in a hospital-based series of 1064 German breast cancer patients and at a 14% carrier frequency in 1014 population controls (OR 0.89, 95%CI 0.69-1.15; p = 0.4). Arg309Cys carriers were not enriched among patients with a family history of breast cancer (OR = 0.87, 95%CI 0.53-1.43, p = 0.6) and were slightly underrepresented in patients with bilateral disease (OR = 0.49, 95%CI = 0.24-0.99; p = 0.047). In the latter group, the mean age at diagnosis was 62 years in carriers and 54 years in non-carriers (p = 0.004). We conclude that there is no evidence for the TOPBP1*Arg309Cys variant to confer an increased risk for breast cancer in the German population.
Role of interleukin-18 in intrahepatic inflammatory cell recruitment in acute liver injury
Authors: Kimura Kiminori , Sekiguchi Satoshi , Hayashi Seishu , Hayashi Yukiko , Hishima Tsunekazu , Nagaki Masahito , Kohara Michinori
Published: November 2010

Although the innate immune system has been demonstrated to play important roles as the first line of defense against various infections, little is known about the interactions between intrahepatic inflammatory cells and the cytokine network in the liver. Here, we examined the role of IL-18 in IHL recruitment in acute liver injury. C57BL/6 mice were injected with an αCD40 mAb, and their serum IL-18 levels were observed to increase, with subsequent recruitment of IHLs into the liver. NKT cells were involved in this liver injury, as the serum ALT levels were reduced in NKT KO mice through the suppression of macrophage and monocyte migration and cytokine production. In contrast, depletion of neutrophils exacerbated the liver injury associated with high levels of TNF-α and IL-18 and increased numbers of macrophages and monocytes. Treatment with a neutralizing antibody against IL-18 reduced the serum ALT levels and inflammatory cell accumulation in the liver. Finally, additional administration of rIL-18 with αCD40 injection caused severe liver injury with increased IFN-γ production by NK cells. In conclusion, these findings demonstrate that IL-18 modulates liver inflammation by the recruitment of inflammatory cells, including NKT cells, macrophages, monocytes, and neutrophils.