bluuebunny/crossref_metadata_2025 huggingface dataset:
High-Density Lipoprotein Induces Proliferation and Migration of Human Prostate Androgen–Independent Cancer Cells by an ABCA1-Dependent Mechanism
Authors: Sekine Yoshitaka , Demosky Steve J. , Stonik John A. , Furuya Yosuke , Koike Hidekazu , Suzuki Kazuhiro , Remaley Alan T.
Published: July 2010

Androgen deprivation therapy for prostate cancer leads to a significant increase of high-density lipoprotein (HDL), which is generally viewed as beneficial, particularly for cardiovascular disease, but the effect of HDL on prostate cancer is unknown. In this study, we investigated the effect of HDL on prostate cancer cell proliferation, migration, intracellular cholesterol levels, and the role of cholesterol transporters, namely ABCA1, ABCG1, and SR-BI in these processes. HDL induced cell proliferation and migration of the androgen-independent PC-3 and DU145 cells by a mechanism involving extracellular signal-regulated kinase (ERK) 1/2 and Akt, but had no effect on the androgen-dependent LNCaP cell, which did not express ABCA1 unlike the other cell lines. Treatment with HDL did not significantly alter the cholesterol content of the cell lines. Knockdown of ABCA1 but not ABCG1 or SR-BI by small interfering RNA (siRNA) inhibited HDL-induced cell proliferation, migration, and ERK1/2 and Akt signal transduction in PC-3 cells. Moreover, after treatment of LNCaP cells with charcoal-stripped fetal bovine serum, ABCA1 was induced ∼10-fold, enabling HDL to induce ERK1/2 activation, whereas small interfering RNA knockdown of ABCA1 inhibited HDL-induced ERK1/2 activation. Simvastatin, which inhibited ABCA1 expression in PC-3 and DU145 cells, attenuated HDL-induced PC-3 and DU145 cell proliferation, migration, and ERK1/2 and Akt phosphorylation. In human prostate biopsy samples, ABCA1 mRNA expression was ∼2-fold higher in the androgen deprivation therapy group than in subjects with benign prostatic hyperplasia or pretreatment prostate cancer groups. In summary, these results suggest that HDL by an ABCA1-dependent mechanism can mediate signal transduction, leading to increased proliferation and migration of prostate cancer cells. Mol Cancer Res; 8(9); 1284–94. ©2010 AACR.
Prevalence of Merkel Cell Polyomavirus among Swiss Merkel Cell Carcinoma Patients
Authors: Mangana Joanna , Dziunycz Piotr , Kerl Katrin , Dummer Reinhard , Cozzio Antonio
Published: July 2010

Background: Merkel cell carcinoma (MCC) is a malignant neuroendocrine neoplasm which shares structural and immunohistochemical features with neuroectodermally derived cells. One hypothesis claims that it arises from Merkel cells, highly innervated neuroendocrine cells involved in mechanoreception in the skin. The incidence rate of this cancer increases with age and sun exposure as well as after immunosuppression. Recently, the clonal integration of a newly identified polyomavirus called Merkel cell polyomavirus (MCPyV) was reported in up to 80% of MCC tissue. Here we report the incidence rate of MCPyV in MCC patients in Switzerland. Methods: We performed polymerase chain reaction in a collection of 32 samples obtained from pathology institutes around Switzerland. We used three different published primer sets. As control groups we used 7 squamous cell carcinoma samples and 11 normal skin samples. Conclusions: We detected viral DNA in 20 out of 30 cases of MCC and in 0 out of 19 control samples. The presence of viral DNA in 66.6% of our MCC tissue specimens confirms the high prevalence of MCPyV in MCC patients described in American, German, French and Hungarian patient collections.
Increased Levels of Soluble LR11 in Cerebrospinal Fluid of Patients with Alzheimer Disease
Authors: Ikeuchi Takeshi , Hirayama Satoshi , Miida Takashi , Fukamachi Isamu , Tokutake Takayoshi , Ebinuma Hiroyuki , Takubo Kohei , Kaneko Hiroyuki , Kasuga Kensaku , Kakita Akiyoshi , Takahashi Hitoshi , Bujo Hideaki , Saito Yasushi , Nishizawa Masatoyo
Published: July 2010

Background: Recent genetic and pathological studies have suggested that a lipoprotein receptor, LR11, is intricately implicated in the pathogenesis of Alzheimer disease (AD). We have recently established a novel sandwich ELISA, which enabled the sensitive quantification of a soluble LR11 (sLR11). By this ELISA, we attempted to determine the difference in the levels of CSF sLR11 in AD patients. Methods: We examined CSF from 29 AD patients, 20 frontotemporal lobar degeneration patients and 27 age-matched control subjects. The CSF sLR11 level as well as the levels of tau and β-amyloid42 (Aβ42) were determined by sandwich ELISA. Results: The CSF tau level and tau/Aβ42 ratio were significantly increased (p < 0.01) in the AD patients. The CSF sLR11 level in the AD patients was significantly higher (p < 0.01) than that of the frontotemporal lobar degeneration patients and the controls. The APOE-Ε4-positive AD patients have higher sLR11 levels than the APOE-Ε4-negative patients (p < 0.01). Conclusions: These results suggest that the quantification of CSF sLR11 may serve as a biomarker of AD, although the diagnostic value for individual patients is limited. An elevated CSF sLR11 level in AD patients may be relevant to AD pathogenesis.
A History of Prior Bare Metal Stent Restenosis Is Associated with Major Adverse Cardiac Events in Subsequent Bare Metal Stenting of de novo Coronary Lesions
Authors: Ferguson Michael A. , Needleman Matthew , Mitchell Eric S. , Carter Luther I. , Bustamante Alexander I. , Love Kathleen M. , Curran Michael J.
Published: July 2010

Objective: To investigate the risk of major adverse cardiac events (MACE) in patients with a history of bare metal stent (BMS) restenosis who undergo subsequent bare metal stenting of a geographically distinct, de novo coronary lesion. Methods: We conducted a retrospective review of 72 BMS procedures performed in geographically distinct, de novo coronary lesions in patients with a history of previous BMS placement at least 3 months prior to the second, index stent procedure. Patients with a history of in-stent restenosis (ISR) were compared with those who had no ISR in their initial stent. Results: Restenosis in the initial BMS was associated with a significant increase in MACE after placement of the index BMS (OR 20.0, 95% CI 3.86–103.58, p < 0.0001). This association was independent of traditional clinical and angiographic risk factors for restenosis. Conclusions: Restenosis of a previously placed BMS is strongly associated with MACE after placement of a subsequent BMS in a de novo coronary lesion.
Sympathetic Stimulation of Adult Cardiomyocytes Requires Association of AKAP5 With a Subpopulation of L-Type Calcium Channels
Authors: Nichols C. Blake , Rossow Charles F. , Navedo Manuel F. , Westenbroek Ruth E. , Catterall William A. , Santana Luis F. , McKnight G. Stanley
Published: July 2010

Rationale:

Sympathetic stimulation of the heart increases the force of contraction and rate of ventricular relaxation by triggering protein kinase (PK)A-dependent phosphorylation of proteins that regulate intracellular calcium. We hypothesized that scaffolding of cAMP signaling complexes by AKAP5 is required for efficient sympathetic stimulation of calcium transients.

Objective:

We examined the function of AKAP5 in the β-adrenergic signaling cascade.

Methods and Results:

We used calcium imaging and electrophysiology to examine the sympathetic response of cardiomyocytes isolated from wild type and AKAP5 mutant animals. The β-adrenergic regulation of calcium transients and the phosphorylation of substrates involved in calcium handling were disrupted in AKAP5 knockout cardiomyocytes. The scaffolding protein, AKAP5 (also called AKAP150/79), targets adenylyl cyclase, PKA, and calcineurin to a caveolin 3–associated complex in ventricular myocytes that also binds a unique subpopulation of Ca
v
1.2 L-type calcium channels. Only the caveolin 3–associated Ca
v
1.2 channels are phosphorylated by PKA in response to sympathetic stimulation in wild-type heart. However, in the AKAP5 knockout heart, the organization of this signaling complex is disrupted, adenylyl cyclase 5/6 no longer associates with caveolin 3 in the T-tubules, and noncaveolin 3–associated calcium channels become phosphorylated after β-adrenergic stimulation, although this does not lead to an enhanced calcium transient. The signaling domain created by AKAP5 is also essential for the PKA-dependent phosphorylation of ryanodine receptors and phospholamban.

Conclusions:

These findings identify an AKAP5-organized signaling module that is associated with caveolin 3 and is essential for sympathetic stimulation of the calcium transient in adult heart cells.
Increasing Cardiac Contractility After Myocardial Infarction Exacerbates Cardiac Injury and Pump Dysfunction
Authors: Zhang Hongyu , Chen Xiongwen , Gao Erhe , MacDonnell Scott M. , Wang Wei , Kolpakov Mikhail , Nakayama Hiroyuki , Zhang Xiaoying , Jaleel Naser , Harris David M. , Li Yingxin , Tang Mingxin , Berretta Remus , Leri Annarosa , Kajstura Jan , Sabri Abdelkarim , Koch Walter J. , Molkentin Jeffery D. , Houser Steven R.
Published: July 2010

Rationale:

Myocardial infarction (MI) leads to heart failure (HF) and premature death. The respective roles of myocyte death and depressed myocyte contractility in the induction of HF after MI have not been clearly defined and are the focus of this study.

Objectives:

We developed a mouse model in which we could prevent depressed myocyte contractility after MI and used it to test the idea that preventing depression of myocyte Ca
2+
-handling defects could avert post-MI cardiac pump dysfunction.

Methods and Results:

MI was produced in mice with inducible, cardiac-specific expression of the β2a subunit of the L-type Ca
2+
channel. Myocyte and cardiac function were compared in control and β2a animals before and after MI. β2a myocytes had increased Ca
2+
current; sarcoplasmic reticulum Ca
2+
load, contraction and Ca
2+
transients (versus controls), and β2a hearts had increased performance before MI. After MI, cardiac function decreased. However, ventricular dilation, myocyte hypertrophy and death, and depressed cardiac pump function were greater in β2a versus control hearts after MI. β2a animals also had poorer survival after MI. Myocytes isolated from β2a hearts after MI did not develop depressed Ca
2+
handling, and Ca
2+
current, contractions, and Ca
2+
transients were still above control levels (before MI).

Conclusions:

Maintaining myocyte contractility after MI, by increasing Ca
2+
influx, depresses rather than improves cardiac pump function after MI by reducing myocyte number.
Increased Risk of Stroke Associated With Nonsteroidal Anti-Inflammatory Drugs
Authors: Chang Chia-Hsuin , Shau Wen-Yi , Kuo Chuei-Wen , Chen Shu-Ting , Lai Mei-Shu
Published: July 2010

Background and Purpose—Limited studies assessed cerebrovascular safety of individual nonsteroidal anti-inflammatory drugs (NSAIDs). We evaluated the risk of ischemic and hemorrhagic stroke associated with short-term use of selective and nonselective NSAIDs in a Chinese population with a high incidence of stroke.

Methods—A retrospective case–crossover study was conducted by analyzing the Taiwan National Health Insurance Database. We identified all ischemic and hemorrhagic stroke patients in 2006, aged ≥20 years, based on International Classification of Diseases, 9th Revision, Clinical Modification diagnosis codes from inpatient claims and defined the index date as the date of hospitalization. For each patient, we defined case period as 1 to 30 days before the index date and control period as 91 to 120 days before the index date. A pharmacy prescription database was searched for NSAID use during the case and control periods. We calculated adjusted ORs and their 95% CIs with a conditional logistic regression model.

Results—A total of 28 424 patients with ischemic stroke and 9456 patients with hemorrhagic stroke were included. For ischemic stroke, a modest increased risk was evident for all oral NSAIDs with adjusted ORs (95% CI) ranging from1.20 (1.00 to 1.44) for celecoxib to 1.90 (1.39 to 2.60) for ketorolac. For hemorrhagic stroke, oral ketorolac was associated with a significantly higher risk with OR of 2.69 (1.56 to 4.66). Significantly increased risk was found for parenteral NSAIDs, in particular ketorolac, with an OR of 3.92 (3.25 to 4.72) for ischemic stroke and 5.98 (4.40 to 8.13) for hemorrhagic stroke.

Conclusions—Use of selective and nonselective NSAIDs was associated with an increased risk of both ischemic and hemorrhagic stroke, strikingly high for parenteral ketorolac.
High-Mobility Group Box 1 Promotes Metalloproteinase-9 Upregulation Through Toll-Like Receptor 4 After Cerebral Ischemia
Authors: Qiu Jianhua , Xu Jian , Zheng Yi , Wei Ying , Zhu Xiaoxia , Lo Eng H. , Moskowitz Michael A. , Sims John R.
Published: July 2010

Background and Purpose—

HMGB1 is a nuclear protein and an alarmin that signals cell damage in response to injury. It is believed that after release from injured cells, HMGB1 binds to its receptors to stimulate cross-talk among cells and to drive components of the inflammatory cascade. This study was intended to investigate the role of extracellular HMGB1 in ischemic stroke by examining the response of the zymogen matrix metalloproteinase-9 (MMP-9) to HMGB1 in vivo and in vitro.

Methods—

Toll-like receptor 2 (TLR2), TLR4, receptor for advanced glycation endproducts (RAGE), and MMP-9 expression was examined using quantitative RT-PCR in primary cultured neurons, astrocytes, and mouse brain after HMGB1 addition. MMP-9 expression/activity was examined using zymography. Middle cerebral artery occlusion was induced for 60 minutes using a filament model.

Results—

TLR4 is constitutively expressed in neurons, astrocytes, and mouse brain. HMGB1 addition to neuronal and glial cell cultures caused MMP-9 upregulation in a dose- and time-dependent manner. Lack of TLR4 function attenuated MMP-9 expression induced by HMGB1 in vitro. After striatal microinjection of HMGB1, MMP-9 was upregulated, and the response was independent of tumor necrosis factor-α. Interestingly, MMP-9 upregulation was reduced in TLR4 missense mutant mice after ischemia compared with wild-type controls, as was infarct volume.

Conclusion—

Our results suggest that HMGB1 triggers MMP-9 upregulation in neurons and astrocytes predominantly via TLR4 after cerebral ischemia. Hence, targeting HMGB1/TLRs signaling pathway may reduce the acute inflammatory response and reduce tissue damage in cerebral ischemia.
The Birth of Esotericism from the Spirit of Protestantism La naissance de l'ésotérisme à partir de l'esprit du protestantisme
Authors: Hanegraaff Wouter
Published: July 2010

Cet article traite de l'émergence et du développement historiques des manières dont nous entendons actuellement l'“ésotérisme occidental” compris comme domaine relativement autonome de la recherche universitaire. Il en traite en explorant un certain nombre de moments possibles de sa “naissance”, en partant du présent et, à partir de là, en remontant dans le temps. Déterminantes pour l'émergence de l'ésotérisme occidental en tant que concept sont les années 1992 (L'ésotérisme, d'Antoine Faivre), 1965 (création de la première chaire d'Histoire de l'ésotérisme occidental, à l'E.P.H.E. [Paris]), 1933 (le début des conférences Eranos), et 1828 (l'Histoire critique du gnosticisme, de Jacques Matter). L'auteur pose qu'en définissant l'ésotérisme en termes de prétention à la connaissance (recherche de connaissance secrète, cachée, dissimulée, supérieure, plus profonde, ou intérieure), les approches traditionnelles, religionistes, aussi bien que les approches discursives contemporaines de l'ésotérisme finissent par en faire un concept théorique aux applications potentiellement universelles et, du même coup, risquent de faire perdre de vue sa spécificité historique. A l'encontre de ces perspectives, l'auteur défend la manière dont Faivre conçoit l'ésotérisme, c'est-à-dire, comme une série de courants historiques ayant donné lieu à un corpus référentiel de textes. Il poursuit en posant que ce que ces courants et ces textes ont en commun n'est pas, comme le dit Faivre, leur participation à une “forme de pensée”, mais leur exclusion, à caractère polémique, de la part d'un discours “anti-apologétique” dans le Protestantisme du 17ème siècle.
Meals and Politics in the Yaad: A Reconsideration
Authors: Eckhardt Benedikt
Published: July 2010

The “Rule of the Community” (1QS) prescribes the organization of meals in a short and not very informative way, which has led to widespread speculations about the cultic significance and/or the political character of meals held in the Yaad. This analysis seeks to show that there is nothing in the Qumran texts which justifies the designation of the meal as either “holy” or “political” in the sense usually given to that term. No anti-Hellenistic attitude is apparent. The meals are political in a different sense, designed to visualize hierarchies and to inscribe them into daily practice. Strategies employed for securing the status of priests make the use of semantics potentially associated with the cult understandable as the attempt to create a frame of reference which makes acceptance of priestly status in the community unavoidable.
Jubilees 46:6‐47:1 and 4QVisions of Amram
Authors: VanderKam James C.
Published: July 2010

The present paper explores the ways in which the authors of the Hebrew Book of Jubilees and the Aramaic Visions of Amram used the motif of a Canaanite-Egyptian war as they labored with the issues raised by the accounts at the end of Genesis and the beginning of Exodus. There is no clear indication that either writer used the work of the other; rather the war in question seems to have been a motif that was available to both when they composed their works and that each adopted and adapted independently.
A Forgotten Reference to Divine Procreation? Psalm 2:6 in Light of Egyptian Royal Ideology
Authors: Granerød Gard
Published: July 2010

The author discusses whether or not MT Ps 2:6 (in particular the verb ) reflects Egyptian royal ideology as the one evident in “Ptah’s Decree to Ramesses”. He tentatively concludes that the verse historically reflects a concept where the god procreates the human king. Semantically, the verb might originally have denoted the emission of semen, either after the model of or at least in a way comparable to “Ptah’s Decree to Ramesses” (c. 13th-11th centuries BCE). The common translation by means of a legal term “to install” etc. reflects the LXX. LXX Ps 2:6 might represent a theological correction of what the translators considered to be a case of an intolerable anthropomorphism in the Hebrew text.
Short Note
Authors: Kirchmayr Karl P.
Published: July 2010

The hypothesis that digits had been written on the wall instead of words provides an illuminating background for understanding the Writing on the Wall and the explanation by Daniel.
Short Note
Authors: Waite Jerry
Published: July 2010

This paper shows that the use of the Hebrew word ‘lp as a troop gives the army size consistent with the Israelite population calculated for the average family, each having three males. The mathematical approach of C. J. Humphreys encounters problems because his assumption about the first-born gives the average Israelite family having 8.7 sons. A possible solution to the census of the 30-50 year old Levites is presented.
The Politics of Ritual Rhetoric: A Proposed Sociopolitical Context for the Redaction of Leviticus 1-16
Authors: Leuchter Mark
Published: July 2010

Recent studies have indicated the rhetorical purpose of Leviticus 1-16 as reification for the ritual authority of the Aaronide priesthood. In the present study, it is suggested that the literary shaping of these chapters was a response to external stimuli that threatened the priesthood. After weighing a variety of historical and socio-political contexts in which such a threat might have emerged, the tenure of Nehemiah as governor is considered as an example of the type of competing leadership typology that encroached upon the priesthood, and the rhetorical features of the Nehemiah Memoir are reconsidered in this light. The redaction of Leviticus 1-16 provides a sacral counter argument to administrative agents such as Nehemiah and his supporters, supporting an ideology where national survival was ensured not through interaction with Persia but through the integrity of Temple ritual entrusted solely to the Aaronide priests.
Amuletic Inscriptions and the Background of YHWH as Guardian and Protector in Psalm 12
Authors: Smoak Jeremy D.
Published: July 2010

The last three verses of Psalm 12 have long posed a variety of problems for interpreters. As a result, a number of studies have argued that certain textual emendations should be made to clarify their meaning. The present study argues that the MT reading should be retained and in fact makes good sense in light of the larger message of the Psalm. In particular, the following contends that the enigmatic phrase blyl in verse 7 should be understood as a reference to the types of Iron Age smelting furnaces, which were partially sunk into the ground. Moreover, the use of the dyad “guard” (šmr) and “protect” (nr) in the following verse is reminiscent of several amulets, which contain these two verbs inscribed on their surfaces. The occurrence of these two verbs on the amulets indicates that they formed a stock protective formula during the Iron Age. As a result, I argue below that the reference to the smelting furnace in verse 7 and the use of the dyad in the following verse allows for a conclusion that the imagery in these verses may have originated from the practice of forming and inscribing metal amulets.
Profanität und Sakralisierung der Beschneidung im Alten Testament
Authors: Wagner Volker
Published: July 2010

Until after the era of exile, (male) circumcision was not widely practiced in Israel nor did it possess any religious or specific cultic significance. Only in very late texts of the Old Testament, dating to the end of the first millennium BC, a theologization and, especially, a sacralisation are attested. This development led to a comprehensive dissemination of the practice of circumcision in Judaism (and Islam).
Royal Recreation: Ivan the Terrible Goes Hunting
Authors: Halperin Charles J.
Published: July 2010

Ivan the Terrible loved hunting but between 1548 and 1564 he seems not to have indulged his favorite pastime. An anonymous English account written 1556-1558 says that Ivan had given hunting up for religious reasons. Three Russian texts written between 1550 and 1563, an entry in the Nikon Chronicle for 1556-1557 which praises Ivan for abstaining from hunting to become a true pastor of his flock, the Domostroi, a book of household management, and two vitae in the Stepennaia kniga tsarskogo rodosloviia (Book of Degrees of Imperial Genealogy), contain diatribes against the cruelty and immorality of hunting. These texts echo a minority anti-hunting tradition in medieval and early modern Europe. As in Europe hunting continued unabated, but in Muscovy it is possible that the anti-hunting animus of these texts inspired at least one temporary convert, Ivan the Terrible himself.
News and Views
Authors: Pawliczak Jakub , Bosek Leszek
Published: July 2010

The Act of 6 November 2008 on Patients’ Rights and the Commissioner for Patients’ Rights collect and safeguard patients’ basic rights as well as provide, for the first time in Poland, an original concept for patients’ collective rights. In addition, the new Act stipulates the specific mechanism for protecting patients’ rights by the newly established body called the Commissioner for Patients’ Rights. Polish reform of medical law will undoubtedly contribute to the expected ratification of the Convention on Human Rights and Biomedicine. However, the nature of codified rights is relatively abstract, and the Act cannot be read without reference to legislation related to physicians and health care institutions.
1903-1914
Authors: Confino Michael
Published: July 2010

From the first years after 1900, the Russian anarchists debated the “question of the organization,” and examined how they should organize the movement so that they may carry on its political activities and secure freedom of expression and of spontaneous action both for its members and for the masses. Opposed as they were to all kind of hierarchic, centralized, and pyramidal types of organization, most of the Russian anarchists preferred the creation of independent and autonomous groups whose members would be linked by a community of ideas and feelings. (The first groups appeared in Russia in 1903.) Under the influence of classical anarchist thinkers like Bakunin, Kropotkin, and Malatesta, some of them saw in anarchism not only an ideology, but a way of life, and tried to create cells in the image of the future society. Everyday realities compelled many of them to adopt more efficient and practical solutions. The most frequent terms used in their vocabulary (and examined here) reveal their state of mind and ways of action, terms such as self-rule, initiative, autonomous action, independence, creativity, and free activity. Their groups were usually homogenous in terms of their social, educational, and national or ethnic composition. They rejected the practice of collecting members' fees or donations. As a result they faced the problem of how to finance their activities. A major debate ensued whether or not to use “expropriations” (eksy), armed attacks on state institutions or private enterprises, for gathering funds, and how such actions were viewed by the masses. The Revolution of 1905, in which the anarchists participated actively, had important repercussions on their views and ways of organizing.
Black Monks and White Gold The Solovetskii Monastery's Prosperous Salt Trade during the Time of Troubles of the Early Seventeenth Century
Authors: Gruber Isaiah
Published: July 2010

This article represents a study of extant business records of the Vologda podvor'e of the Solovotskii Monastery from the Time of Troubles (1598-1613). The archival records show that the monastery continued to take in impressive sums from its salt trade during this period of crisis, and in fact was able to increase its revenue during the first two thirds of the Troubles. The study additionally demonstrates that both prices and sales volume oscillated (rose and fell) in a yearly pattern. However, over the longer term, volume remained constant while prices rose, thus producing the increase in net income. The detailed records of prices also enable a comparison to the late Prof. Hellie's data set in The Ecomomy and Material Culture of Russia. The Solovki salt prices recorded at Vologda manifest distinct price levels and behavior and thus significantly enhance Hellie's charts for the Time of Troubles period. The study as a whole illustrates that the Time of Troubles exerted quite an uneven effect on the population of Muscovy, with the wealthy monasteries often economically unaffected or at least less affected than the general population. It also reveals the extent to which economic profit remained a principal driving force of the monasterial “corporation” at this time.
“National Identity in Premodern Rus”
Authors: Halperin Charles
Published: July 2010

This article is a commentary on some of the conclusions of Serhii Plokhy's The Origin of the Slavic Nations. Premodern Identities in Russia, Ukraine and Belarus. Plokhy addressed ethnocultural (national) identities and national identity projects from the tenth to the early eighteenth century. This essay is concerned with Kievan Rus', the Mongol impact on the East Slavs, and Muscovite history from the fourteenth to the sixteenth century. It offers alternative interpretations both of the historical background which Plokhy outlines for the evolution of East Slavic peoples and of Plokhy's interpretations of various historical, political, religious and literary texts. The chronology of the translatio of the myth of the Rus' Land from Kievan Rus' to Moscow is still a matter of contention. In synthesizing the views of such historians as Edward Keenan and Donald Ostrowski, Plokhy has attributed too much influence to the Mongols on Russian institutional and cultural history. Plokhy has failed to be consistent in his application of Keenan's criticism of sources and Keenan's concept of sixteenth-century Muscovite society and culture. Finally, Plokhy somewhat oversimplifies the cultural heterogeneity of Ivan the Terrible and Ivan the Terrible's Muscovy. These criticisms are a tribute to Plokhy's challenging but inspiring monograph.
Aleksei Kurbatov, Vasilii Tatishchev and the Testament of Ivan the Terrible of 1572
Authors: Soldat Cornelia
Published: July 2010

The only surviving copy of a Testament of Ivan the Terrible stems from the beginning of the 19th century with a watermark from 1805. In January 1822 the director of the Foreign Office's archive, Aleksei Malinovskii, sent the testament to the historian and novelist Nikolai Karamzin, who was working on his History of the Russian State, and who published it in the commentary to the ninth volume of the History. An analysis of Aleksei Kurbatov's and Vasilii Tatishchev's alledged authorship of the testament's preface and commentary leads to the conclusion that the testament displays the literary devices of a fictional text. The preface presents a story complete with the grammatically ambiguous signature ,,A. Kurbatova“, a host of conflicting dates and several lost copies of a lost original. The argument for Tatishchev's authorship rests solely on some peculiarities concerning the publications of his personal copy of the Sudebnik of 1550. The questions surrounding the testament are resolved easily when one takes into account the literary hints and regards the text as an early 19th-century mystification.
The Munker–White Effect and Chromatic Induction Share Similar Nonlinear Response Properties
Authors: Chen Chien-Chung , Chien Sarina Hui-Lin , Lin Yong-Jun
Published: July 2010

The brightness or color appearance of a region may be altered by the presence of a pattern surrounding it in the visual field. The Munker–White effect (grating surround) and brightness or color induction from concentric annuli ('bull's-eye' surround) are two examples. We examined whether these two phenomena share similar properties. In the asymmetric matching experiment, the task of an observer was to adjust the appearance of a matching patch to match the appearance of a test patch embedded in one of the two types (square wave grating or concentric annuli) of inducing surrounds (inducers). The inducer modulated in one of three color directions (isochromatic: ±(L + M + S) and isoluminance: ±(L – M) or ±S). Each inducer type and color direction had two opposing phases and four contrast levels. The results show that the induced appearance shift increases as a power function of the inducer contrast, regardless of the spatial configuration of the inducer. Further analysis showed that a sensitivity modulation model of lateral interaction could explain both induction effects.
Using Team‐based Learning to Teach Clinical Pharmacology in Medical School: Student Satisfaction and Improved Performance
Authors: Zgheib N. K. , Simaan J. A. , Sabra R.
Published: July 2010

Formal teaching in clinical pharmacology was never part of the curriculum at the American University of Beirut Faculty of Medicine. Based on feedback from students and on recommendations of academic bodies, we have introduced, since June 2008, twice‐monthly “rational prescribing” sessions during the required internal medicine rotation in year 4 of medical school. All sessions were designed according to the innovative Team‐based Learning format and concluded by having the students practice prescription writing and personal formulary development based on the World Health Organization criteria. Our 18‐month experience showed that students were very satisfied with the course and the teaching approach, and that their performance on prescription writing and formulary development had improved. Although further studies are needed to explore the impact of team‐based learning on additional performance measures, we recommend it as an effective alternative for teaching clinical pharmacology in medical schools.
Effectiveness of antiepileptic or antidepressant drugs when added to opioids for cancer pain: systematic review
Authors: Bennett Michael I
Published: July 2010

Neuropathic pain mechanisms are present in up to 40% of patients with cancer pain. In these situations, additional or adjuvant analgesic drugs (such as antidepressants or antiepileptics) are often required to optimize pain control alongside standard opioid therapy. This systematic review aimed to determine the effectiveness of antidepressants and antiepileptics when added to opioids, compared to opioids alone, for the management of pain caused directly by cancer. Prospective clinical studies, published in English that used a before-after design or randomized or non-randomized group comparisons were identified. Data were extracted on pain intensity, pain relief and adverse events. Eight studies were eligible (five randomized controlled trials) that recruited 465 patients in total, of whom 370 (79.5%) completed the study period. A narrative analysis was performed because clinical and methodological heterogeneity prevented meta-analysis.

Included studies suggested that adjuvants improve pain control within 4–8 days when added to opioids for cancer pain; the strongest evidence supports gabapentin. However, a reduction in pain intensity of greater than 1 point on a 0–10 numerical rating scale is unlikely, but an increase in adverse events is likely. For all adjuvants, the effect size was much less than that seen in patients with non-cancer neuropathic pain. Dosing strategies that can be examined in future clinical trials are suggested.
The Effect of Health State Selection on the Valuation of EQ-5D
Authors: Chuang Ling-Hsiang , Kind Paul
Published: July 2010

Background. Many aspects of valuation study designs are poorly understood, and the size and composition of health states used in valuation studies vary widely. Our aims were to investigate the impact of the selection of a subset of EQ-5D health states in generating a set of visual analog scale (VAS)–based values. Our aims were to investigate the optimal number of health states, the sample size required per health state, and which combinations of health states are required to establish a EQ-5D VAS value set. Methods. Data were drawn from a United Kingdom (UK) general population postal survey in which all health states defined by EQ-5D were evaluated using VAS. We used a simulation approach to address each question, and the performance of each estimation model was assessed by the average value of the mean absolute errors. Results. Despite the constraint of the small sample size in the study dataset, the results suggest that the optimal number of states for a valuation study is 32, 100 observations per health state were sufficient, and multiple subsets of health states were feasible. Conclusions. Selecting health states not included in the “Measurement and Valuation of Health” dataset in valuation studies is quite specifically encouraged. However, it remains prudent to ensure that the selection of health states covers as wide a range of severity as possible. Setting the number of observations per health state to 150 might allow for correction of any errors in data collection or processing. The extent to which the results of this study based on VAS valuation data can be safely generalized to the design of time tradeoff valuation studies remains an open question.
Are Medical Outcomes Fungible? A Survey of Voters, Medical Administrators, and Physicians
Authors: DeKay Michael L.
Published: July 2010

Purpose. Many analyses of medical treatments entail the aggregation of health outcomes over patients and over time. This study assessed the extent to which voters, medical administrators, and physicians consider such aggregation to be appropriate. In addition, the study assessed whether this perceived fungibility of outcomes moderates the difference between treatment recommendations in single-play decisions (for 1 patient on 1 occasion) and those in repeated-play decisions (for several patients or for 1 patient on several occasions). Methods. In a 5-contact mail survey of registered voters ( n = 182, response rate = 52%), medical administrators ( n = 123, 35%), and physicians ( n = 95, 26%), respondents rated the fungibility of outcomes and indicated their preferred action in 1 of 3 scenarios involving changes in life expectancy or the duration of pain. They evaluated a risky, positive-expected-value treatment in a single-play decision, then in a repeated-play decision, and again in a repeated-play decision after they viewed the distribution of possible net outcomes. Results. Perceived fungibility varied substantially across respondents in all groups, with voters giving higher fungibility ratings than administrators or physicians. Respondents’ strength-of-preference ratings for treatment increased from single-play to repeated-play decisions, but these increases were moderated by perceived fungibility, as expected. When outcomes were considered fungible, treatments were much more attractive in repeated-play decisions than in single-play decisions. When outcomes were considered nonfungible, there was essentially no difference between single- and repeated-play decisions. Conclusions. Recommendations regarding risky medical treatments with positive expectations appear to depend, in part, on opinions about whether it is reasonable to aggregate medical outcomes over patients or over time. Such opinions vary widely among physicians and others.
What Makes a Tumor Diagnosis a Call to Action? On the Preference for Action versus Inaction
Authors: Gavaruzzi Teresa , Lotto Lorella , Rumiati Rino , Fagerlin Angela
Published: July 2010

Background. Many studies have shown an omission bias, but when the context is cancer, people seem to prefer active treatments to watchful waiting. Objective. First, to investigate whether the preference for active treatment for cancer could depend on the associations attached to the inaction option, and second, to explore the kind of diagnosis that gives rise to the preference for action, by comparing scenarios differing in the status of the illness (already present v. could arise in the future), the kind of diagnosis (malign tumor, benign tumor, or nontumor), and the possible development of the tumor (growth v. degeneration). Design. Between-subjects design with 8 hypothetical scenarios. Participants. A total of 735 students participated in an Internet survey. Measurements. Choice between watchful waiting and surgery, perceived severity of the diagnosis. Results. Active treatment was preferred only when the scenario described watchful waiting as excluding surgery in the future. The critical aspect for participants’ preference for active treatment was the malignancy of the tumor currently diagnosed. Perceived severity was also a significant predictor of treatment choice. Limitations. Inability to infer causation in the relationship between choice and perceived severity. Conclusions. Action is preferred to inaction when a malignant tumor is currently diagnosed and active treatments are not allowed in the future; under other conditions, participants prefer inaction (e.g., when active treatments are allowed in the future, or when the tumor is benign) or exhibit no preference (e.g., when it is not specified whether active treatments are allowed in the future).
Injuries to the Pectoralis Major Muscle
Authors: Provencher CDR Matthew T. , Handfield Kent , Boniquit Nicole T. , Reiff Stefanie N. , Sekiya Jon K. , Romeo Anthony A.
Published: July 2010

Injuries to the pectoralis major muscle are relatively infrequent but result in pain, weakness, and deformity of the upper extremity. The usual injury mechanism is during eccentric shortening of the pectoralis major under heavy load, such as when performing a bench press exercise. The ability to detect and treat a pectoralis major rupture is important for both the clinician and the patient and is aided with knowledge of the anatomy, the clinical findings, and results of nonoperative and operative care. It is important to understand the physical demands and desires of the patient as well as to understand the outcomes of both nonoperative and operative care to make an informed decision regarding optimal treatment. This article highlights the importance of the clinical examination in identifying the injury, examines various surgical techniques to repair the rupture, and reports on potential complication and reinjury rates.
Anatomic Posterolateral Knee Reconstructions Require a Popliteofibular Ligament Reconstruction Through a Tibial Tunnel
Authors: McCarthy Mark , Camarda Lawrence , Wijdicks Coen A. , Johansen Steinar , Engebretsen Lars , LaPrade Robert F.
Published: July 2010

Background: No biomechanical study has been performed analyzing the merits of reconstructing the popliteofibular ligament (PFL) through a tibial tunnel with an anatomic reconstruction of the posterolateral knee.

Hypothesis: There is no difference in an anatomic posterolateral knee reconstruction with or without a PFL reconstruction placed through a tibial tunnel in restoring knee motion to the intact, uninjured state, and the knee is not overconstrained with this reconstruction.

Study Design: Controlled laboratory study.

Methods: Eight paired knees were tested in the intact state and then sectioned to simulate a grade III posterolateral knee injury. The reconstruction for the first paired knee reconstructed the PFL (through a tibial tunnel), popliteus tendon, and fibular collateral ligament (group 1); the matched knee reconstruction involved only the popliteus tendon and fibular collateral ligament (group 2).

Results: Reconstructions for group 1 knees restored knee motion to the intact state for all tested conditions at all knee flexion angles with no overconstraint of the knee. Without reconstructing the PFL (group 2), small but significant increases in motion were found for varus translation at 0° (3.0°), 20° (3.1°), and 60° (3.8°) of knee flexion compared with the intact state. At 60° and 90° of flexion, the reconstruction for group 2 had small but significant increases in internal rotation compared with the intact state (1.3° and 1.8°, respectively).

Conclusion: Inclusion of the PFL through a tibial tunnel as part of an anatomic posterolateral knee reconstruction restores knee stability back to the intact state and does not overconstrain the knee. Furthermore, inclusion of the PFL through a tibial tunnel restored normal internal rotation.

Clinical Relevance: The PFL should be included in anatomic reconstructions of grade III posterolateral knee injuries with placement through a tibial tunnel to best restore the intact, preinjury knee motion state and, most notably, normal internal rotation without evidence of overconstraint of the knee.
Cell-cycle blockage associated with increased apoptotic cells in the thymus of chickens fed on diets high in fluorine
Authors: Tao Chen  , Hengmin Cui  , Yun Cui  , Caimin Bai  , Tao Gong  , Xi Peng
Published: July 2010

Three hundred 1-day-old Avian broilers were divided into four groups and fed on control diet (fluorine 23 mg/kg) and high-fluorine (F) diets (400 mg/kg, high-F group I; 800 mg/kg, high-F group II; 1200 mg/kg, high-F group III) for 42 days (n = 75/group). The growth index (GI) was obviously decreased in the three high-F groups, which indicated the inhibited development of thymus. Histopathologically, the population of thymocytes was decreased in the thymic lobule in the three high-F groups. As measured by flow cytometry, thymocytes in G0/G 1 phase were significantly increased while thymocytes in S phase, G 2 + M phase and proliferating index (PI) value were obviously decreased in the three high-F groups. Also, the percentage of apoptotic thymocytes was greatly increased in the three high-F groups when compared with that of control group. At the same time, the occurrence frequencies of apoptotic thymocyte were markedly increased in the three high-F groups, with the appearance of dilated endoplasmic reticulum in high-F groups II and III ultra-structurally. The results showed that excess dietary F in the range of 400-1200 mg/kg caused histological lesions, G0/G1 arrest and cellular apoptosis in the thymus, which inhibited the development of thymus and finally led to impaired cellular immune function.
Thrombocytopenia associated with galsulfase treatment
Authors: Doğan Murat , Cesur Yasar , Peker Erdal , Oner Ahmet F , Dogan Sekibe Zehra
Published: July 2010

Mucopolysaccharidosis type VI (MPS VI), or Maroteaux-Lamy syndrome, is a lysosomal storage disorder that results from a deficiency of the enzyme N-acetylgalactosamine-4-sulfatase or arylsulfatase B (ASB). It is a relatively rare disorder, with an estimated incidence of 1 in 248,000 to 1 in 300,000. The diagnosis is made on the basis of findings of elevated urine glycosaminoglycans and a deficiency of ASB activity in leukocytes or cultured fibroblasts. In treatment of MPS VI, enzyme replacement therapy (galsulfase; human recombinant ASB enzyme) became available. Infusions of galsulfase were generally well tolerated. But in some patients, infusion-associated reactions including rash, urticaria, headache, hypotension, nausea, and vomiting were documented and were managed successfully by interrupting or slowing the rate of infusion and/or by the administration of antihistamines, antipyretics, corticosteroids, or oxygen. Here, we report a case with MPS VI who developed thrombocytopenia after third dose of therapy. To the best of our knowledge, this is the first report about thrombocytopenia associated with galsulfase therapy in the literature. Additionally, with this report, we want to share our approach for this case.
An unusual case of mesalazine intoxication: Oral and rectal overloading of the rectal suppository form
Authors: Koseoglu Zikret , Satar Salim , Kara Banu , Sebe Ahmet , Kosenli Ozgun
Published: July 2010

Drugs containing 5-acetylsalicylic acid (5-ASA) have been commonly used for inflammatory bowel diseases for more than half a century, but no case about overdose of suppository form of mesalazine which was taken both orally and rectally has been reported in the related literature up to now. In the present case, a 20-year-old male patient who took 14.5 g of mesalazine rectally and orally for suicide purpose is discussed. He was an ulcerative colitis patient and depressed about his illness and routine life traffic. Although it was hard for him to take the suppository form orally because of its bad taste and structure, he took it with the help of water. In the patient’s colonoscopy, diffuse hyperemia and edema extending from the anal channel to the proximal rectal mucosa and a 1.5 cm diameter ulcer expanding from anal channel through the rectum were identified. No pathology was found in the upper gastrointestinal endoscopy. Routine laboratory examination was performed and no abnormality was identified in the patient’s total blood account, biochemical parameters and full-urine examination. In the control rectoscopy applied to the patient 15 days later, recovery of the ulcer was observed and he was discharged to be followed in the psychiatry clinic.
A double-suicide autopsy case of potassium poisoning by intravenous administration of potassium aspartate after intake of some psychopharmaceuticals
Authors: Watanabe K. , Hasegawa K. , Suzuki O.
Published: July 2010

We report a curious double-suicide autopsy case of both male and female who died of potassium poisoning by intravenous administration of concentrated potassium aspartate solution. The plasma concentrations of potassium of the male and female subjects were as high as 49.7 and 62.8 mEq/L, respectively. In addition to the high concentrations of potassium, toxic levels of phenobarbital, promethazine and chlorpromazine, and relatively low levels of etizolam and brotizolam were also detected from whole blood and urine specimens of both cadavers. Twenty empty plastic bottles (10-mL capacity) labeled ‘ASPARA® Potassium Injection 10 mEq’ were found at the suicide spot. To our knowledge, this is the first description for suicidal death by potassium aspartate; in all of the previous literature, they used potassium chloride intravenously or per os.