bluuebunny/crossref_metadata_2025 huggingface dataset:
Starting with ultrasonography decreases popliteal block performance time in inexperienced hands: a prospective randomized study
Authors: Cataldo Rita , Carassiti Massimiliano , Costa Fabio , Martuscelli Matteo , Benedetto Maria , Cancilleri Francesco , Marinozzi Andrea , Martinelli Nicolò
Published: December 2012

Background

The widespread of hallux valgus surgery in a day care setting enhanced the role of regional anaesthesia in the last few years. Sciatic nerve block at popliteal fossa has been shown to provide safe and effective analgesia. Our purpose was to compare the success rate and performance time of popliteal block during resident’s training for regional anaesthesia by using nerve stimulation (NS) or combined nerve stimulation and ultrasound (NS + US).

Methods

70 adult patients undergoing hallux valgus surgery were randomly assigned to receive sciatic nerve block at popliteal fossa with US+NS or NS alone with a double injection technique for peroneal and tibial branches, respectively. Two residents experienced with nerve stimulator performed the procedures after a learning phase concerning ultrasonography. A local anaesthetic solution, containing 10 mL of 0.75% ropivacaine and 10 mL of 2% lidocaine was used: 12 mL were infiltrated close the tibial nerve, and 8mL were infiltrated close the common peroneal nerve. Block success rate, sensory block onset time, block performance time were evaluated. Recourse to general anaesthesia was considered as failure.

Results

No differences were detected in success rate and onset time of sensory block between the two groups (P > 0.05). The time to block tibial nerve and the overall block time were significantly faster in US+NS group (P < 0.05).

Conclusions

Ultrasound guidance for popliteal nerve block resulted in similar success rate with a faster procedure time when compared with nerve stimulator, thus providing a possible effect on resident education and operating room efficiency.
Genome-wide sequencing for the identification of rearrangements associated with Tourette syndrome and obsessive-compulsive disorder
Authors: Hooper Sean D , Johansson Anna CV , Tellgren-Roth Christian , Stattin Eva-Lena , Dahl Niklas , Cavelier Lucia , Feuk Lars
Published: December 2012

Background

Tourette Syndrome (TS) is a neuropsychiatric disorder in children characterized by motor and verbal tics. Although several genes have been suggested in the etiology of TS, the genetic mechanisms remain poorly understood.

Methods

Using cytogenetics and FISH analysis, we identified an apparently balanced t(6,22)(q16.2;p13) in a male patient with TS and obsessive-compulsive disorder (OCD). In order to map the breakpoints and to identify additional submicroscopic rearrangements, we performed whole genome mate-pair sequencing and CGH-array analysis on DNA from the proband.

Results

Sequence and CGH array analysis revealed a 400 kb deletion located 1.3 Mb telomeric of the chromosome 6q breakpoint, which has not been reported in controls. The deletion affects three genes (GPR63, NDUFA4 and KLHL32) and overlaps a region previously found deleted in a girl with autistic features and speech delay. The proband’s mother, also a carrier of the translocation, was diagnosed with OCD and shares the deletion. We also describe a further potentially related rearrangement which, while unmapped in Homo sapiens, was consistent with the chimpanzee genome.

Conclusions

We conclude that genome-wide sequencing at relatively low resolution can be used for the identification of submicroscopic rearrangements. We also show that large rearrangements may escape detection using standard analysis of whole genome sequencing data. Our findings further provide a candidate region for TS and OCD on chromosome 6q16.
Spending on vegetable and fruit consumption could reduce all-cause mortality among older adults
Authors: Lo Yuan-Ting , Chang Yu-Hung , Wahlqvist Mark L , Huang Han-Bin , Lee Meei-Shyuan
Published: December 2012

Background

Few studies have evaluated the linkage between food cost and mortality among older adults. This study considers the hypothesis that greater food expenditure in general, and particularly on more nutritious plant and animal-derived foods, decreases mortality in older adults.

Methods

This study uses the 1999–2000 Elderly Nutrition and Health Survey in Taiwan and follows the cohort until 2008, collecting 24-hr dietary recall data for 1781 participants (874 men and 907 women) aged 65 y or older. Using monthly mean national food prices and 24-hr recall, this study presents an estimate of daily expenditures for vegetable, fruit, animal-derived, and grain food categories. Participants were linked to the national death registry.

Results

Of the 1781 original participants, 625 died during the 10-y follow-up period. Among the 4 food categories, the fourth and fifth expenditure quintiles for vegetables and for fruits had the highest survival rates. After adjusting for co-variates, higher (Q4) vegetable and higher fruit (Q4) food expenditures referent to Q1 were significantly predictive of reduced mortality (HR = 0.55, 95% CI: 0.39-0.78 and HR = 0.64, 95% CI: 0.42–0.99, respectively) and the risk decreased by 12% and 10% for every NT$15 (US$0.50) increase in their daily expenditures. Animal-derived and grain food spending was not predictive of mortality.

Conclusion

Greater and more achievable vegetable and fruit affordability may improve food security and longevity for older adults.
Design and analysis issues in gene and environment studies
Authors: Liu Chen-yu , Maity Arnab , Lin Xihong , Wright Robert O , Christiani David C
Published: December 2012

Both nurture (environmental) and nature (genetic factors) play an important role in human disease etiology. Traditionally, these effects have been thought of as independent. This perspective is ill informed for non-mendelian complex disorders which result as an interaction between genetics and environment. To understand health and disease we must study how nature and nurture interact. Recent advances in human genomics and high-throughput biotechnology make it possible to study large numbers of genetic markers and gene products simultaneously to explore their interactions with environment. The purpose of this review is to discuss design and analytic issues for gene-environment interaction studies in the “-omics” era, with a focus on environmental and genetic epidemiological studies. We present an expanded environmental genomic disease paradigm. We discuss several study design issues for gene-environmental interaction studies, including confounding and selection bias, measurement of exposures and genotypes. We discuss statistical issues in studying gene-environment interactions in different study designs, such as choices of statistical models, assumptions regarding biological factors, and power and sample size considerations, especially in genome-wide gene-environment studies. Future research directions are also discussed.
Sevoflurane reduces clinical disease in a mouse model of multiple sclerosis
Authors: Polak Paul E , Dull Randall O , Kalinin Sergey , Sharp Anthony J , Ripper Richard , Weinberg Guy , Schwartz David E , Rubinstein Israel , Feinstein Douglas L
Published: December 2012

Background

Inhalational anesthetics have been shown to influence T cell functions both in vitro and in vivo, in many cases inducing T cell death, suggesting that exposure to these drugs could modify the course of an autoimmune disease. We tested the hypothesis that in mice immunized to develop experimental autoimmune encephalomyelitis (EAE), a well established model of multiple sclerosis (MS), treatment with the commonly used inhalational anesthetic sevoflurane would attenuate disease symptoms.

Methods

C57Bl6 female mice were immunized with myelin oligodendrocyte glycoprotein (MOG) peptide residues 35 to 55 to induce a chronic demyelinating disease. At day 10 after immunization, the mice were subjected to 2 h of 2.5% sevoflurane in 100% oxygen, or 100% oxygen, alone. Following treatment, clinical scores were monitored up to 4 weeks, after which brain histology was performed to measure the effects on astrocyte activation and lymphocyte infiltration. Effects of sevoflurane on T cell activation were studied using splenic T cells isolated from MOG peptide-immunized mice, restimulated ex vivo with MOG peptide or with antibodies to CD3 and CD28, and in the presence of different concentrations of sevoflurane. T cell responses were assessed 1 day later by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay for proliferation, lactate dehydrogenase (LDH) release for cell death, and inflammatory activation by production of interleukin (IL)-17 and interferon (IFN)γ.

Results

Clinical scores in the oxygen-treated group increased until day 28 at which time they showed moderate to severe disease (average clinical score of 2.9). In contrast, disease progression in the sevoflurane-treated group increased to 2.1 at day 25, after which it remained unchanged until the end of the study. Immunohistochemical analysis revealed reduced numbers of infiltrating leukocytes and CD4+ cells in the CNS of the sevoflurane-treated mice, as well as reduced glial cell activation. In splenic T cells, low doses of sevoflurane reduced IFNγ production, cell proliferation, and increased LDH release.

Conclusions

These results are the first to show attenuation of EAE disease by an inhaled anesthetic and are consistent with previous reports that inhaled anesthetics, including sevoflurane, can suppress T cell activation that, in the context of autoimmune diseases such as MS, could lead to reduced clinical progression.
Susceptibility of juvenile and adult blood–brain barrier to endothelin-1: regulation of P-glycoprotein and breast cancer resistance protein expression and transport activity
Authors: Harati Rania , Villégier Anne-Sophie , Banks William A , Mabondzo Aloise
Published: December 2012

Background

P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) play a critical role in keeping neurotoxic substances from entering the brain. We and others have previously reported an impact of inflammation on the regulation of adult blood–brain barrier (BBB) efflux transporters. However, studies in children have not been done. From the pediatric clinical perspective, it is important to understand how the central nervous system (CNS) and BBB drug efflux transporters differ in childhood from those of adults under normal and inflammatory conditions. Therefore, we examined and compared the regulation of P-gp and BCRP expression and transport activity in young and adult BBB and investigated the molecular mechanisms underlying inflammatory responses.

Methods

Rats at postnatal day (P) P21 and P84, corresponding to the juvenile and adult stages of human brain maturation, respectively, were treated with endothelin-1 (ET-1) given by the intracerebroventricular (icv) route. Twenty-four hours later, we measured P-gp and BCRP protein expression in isolated brain capillary by immunoblotting as well as by transport activityin vivoby measuring the unbound drug partitioning coefficient of the brain (Kp,uu,brain) of known efflux transporter substrates administered intravenously. Glial activation was measured by immunohistochemistry. The release of cytokines/chemokines (interleukins-1α, 1-β (IL-1β), -6 (IL-6), -10 (IL-10), monocyte chemoattractant protein (MCP-1/CCL2), fractalkine and tissue inhibitor of metalloproteinases-1 (TIMP-1)) were simultaneously measured in brain and serum samples using the Agilent Technology cytokine microarray.

Results

We found that juvenile and adult BBBs exhibited similar P-gp and BCRP transport activities in the normal physiological conditions. However, long-term exposure of the juvenile brain to low-dose of ET-1 did not change BBB P-gp transport activity but tended to decrease BCRP transport activity in the juvenile brain, while a significant increase of the activity of both transporters was evidenced at the BBB in the adult brain. Moreover, juvenile and adult brain showed differences in their expression profiles of cytokines and chemokines mediated by ET-1.

Conclusions

BBB transporter activity during neuroinflammation differs between the juvenile and adult brains. These findings emphasize the importance of considering differential P-gp and BCRP transport regulation mechanisms between adult and juvenile BBB in the context of neuroinflammation.
Inflorescence stem grafting made easy in Arabidopsis
Authors: Nisar Nazia , Verma Shelley , Pogson Barry J , Cazzonelli Christopher I
Published: December 2012

Background

Plant grafting techniques have deepened our understanding of the signals facilitating communication between the root and shoot, as well as between shoot and reproductive organs. Transmissible signalling molecules can include hormones, peptides, proteins and metabolites: some of which travel long distances to communicate stress, nutrient status, disease and developmental events. While hypocotyl micrografting techniques have been successfully established for Arabidopsis to explore root to shoot communications, inflorescence grafting in Arabidopsis has not been exploited to the same extent. Two different strategies (horizontal and wedge-style inflorescence grafting) have been developed to explore long distance signalling between the shoot and reproductive organs. We developed a robust wedge-cleft grafting method, with success rates greater than 87%, by developing better tissue contact between the stems from the inflorescence scion and rootstock. We describe how to perform a successful inflorescence stem graft that allows for reproducible translocation experiments into the physiological, developmental and molecular aspects of long distance signalling events that promote reproduction.

Results

Wedge grafts of the Arabidopsis inflorescence stem were supported with silicone tubing and further sealed with parafilm to maintain the vascular flow of nutrients to the shoot and reproductive tissues. Nearly all (87%) grafted plants formed a strong union between the scion and rootstock. The success of grafting was scored using an inflorescence growth assay based upon the growth of primary stem. Repeated pruning produced new cauline tissues, healthy flowers and reproductive siliques, which indicates a healthy flow of nutrients from the rootstock. Removal of the silicone tubing showed a tightly fused wedge graft junction with callus proliferation. Histological staining of sections through the graft junction demonstrated the differentiation of newly formed vascular connections, parenchyma tissue and lignin accumulation, supporting the presumed success of the graft union between two sections of the primary inflorescence stem.

Conclusions

We describe a simple and reliable method for grafting sections of an Arabidopsis inflorescence stem. This step-by-step protocol facilitates laboratories without grafting experience to further explore the molecular and chemical signalling which coordinates communications between the shoot and reproductive tissues.
Efficacy of renal replacement therapy in critically ill patients: a propensity analysis
Authors: Clec'h Christophe , Darmon Michaël , Lautrette Alexandre , Chemouni Frank , Azoulay Elie , Schwebel Carole , Dumenil Anne-Sylvie , Garrouste-Orgeas Maïté , Goldgran-Toledano Dany , Cohen Yves , Timsit Jean-François
Published: December 2012

Introduction

Although renal replacement therapy (RRT) is a common procedure in critically ill patients with acute kidney injury (AKI), its efficacy remains uncertain. Patients who receive RRT usually have higher mortality rates than those who do not. However, many differences exist in severity patterns between patients with and those without RRT and available results are further confounded by treatment selection bias since no consensus on indications for RRT has been reached so far. Our aim was to account for these biases to accurately assess RRT efficacy, with special attention to RRT timing.

Methods

We performed a propensity analysis using data of the French longitudinal prospective multicenter Outcomerea database. Two propensity scores for RRT were built to match patients who received RRT to controls who did not despite having a close probability of receiving the procedure. AKI was defined according to RIFLE criteria. The association between RRT and hospital mortality was examined through multivariate conditional logistic regression analyses to control for residual confounding. Sensitivity analyses were conducted to examine the impact of RRT timing.

Results

Among the 2846 study patients, 545 (19%) received RRT. Crude mortality rates were higher in patients with than in those without RRT (38% vs 17.5%, P < 0.001). After matching and adjustment, RRT was not associated with a reduced hospital mortality. The two propensity models yielded concordant results.

Conclusions

In our study population, RRT failed to reduce hospital mortality. This result emphasizes the need for randomized studies comparing RRT to conservative management in selected ICU patients, with special focus on RRT timing.
Timing of dialysis initiation in AKI in ICU: international survey
Authors: Thakar Charuhas V , Rousseau James , Leonard Anthony C
Published: December 2012

Introduction

Initiating dialysis in acute kidney injury (AKI) in an intensive care unit (ICU) remains a subjective clinical decision. We examined factors and practice patterns that influence early initiation of dialysis in ICU patients with acute kidney injury.

Methods

An online survey presented nephrologists (international) with three case scenarios with unstated predicted mortality rates of < 10%, 10 - 30% and > 30%. For each case the respondents were asked 4 questions about influences on the decision whether or not to initiate dialysis within 24 hours: Q1, likelihood of initiating dialysis; Q2, threshold of BUN levels (< 50, 50 - 75, 76 - 100, > 100 mg/dl) considered relevant to this decision; Q3, magnitude of creatinine elevation (two to three-fold increase; greater than threefold increase; absolute level > 5 mg/dl regardless of change) considered relevant; Q4, a rank order of the influence of five parameters (BUN level, change of creatinine from baseline, oxygen saturation, potassium level, and urine output), 1 being the most influential and 5 being the least influential.

Results

One hundred seventy-two nephrologists (73% in practice for > 5 years; 70% from the U.S.A.) responded to the survey. The proportion of subjects likely to initiate early dialysis increased (76% to 94%), as did the predicted mortality (p < 0.001). The proportion of subjects considering early dialysis at a BUN level ≤ 75 increased from 17% to 30 to 40% as the predicted mortality of the cases increased (p < 0.0001). The proportion of subjects choosing absolute creatinine level to be more influential than relative increment, went from 60% to 54% to 43% as predicted mortality increased (p < 0.0001). Rank-order analysis indicated that influence of oxygen saturation and potassium level on dialysis decision showed a significant change with severity of illness, but BUN level and creatinine elevation remained less influential, and did not change with severity.

Conclusions

Severely ill patients were more likely to be subjected to early dialysis initiation, but its utility is not clear. Rank-order analysis indicates dialysis initiation is still influenced by "imminent" indications rather than a "proactive" decision based on the severity of AKI or azotemia.
Crosstalk between neutrophils and dendritic cells: a context-dependent process
Authors: Schuster Steffen , Hurrell Benjamin , Tacchini-Cottier Fabienne
Published: December 2012

Neutrophils are massively and rapidly recruited following infection. They migrate to the site of acute infection and also transiently to dLNs. In addition to their well-established role as microbial killers, accumulating evidence shows that neutrophils can play an immunoregulatory role. Neutrophils were recently shown to influence the activation of different leukocyte types including NK cells, B cells, and DCs. DCs are professional APCs playing a key role to the launching and regulation of the immune response; thus, crosstalk between neutrophils and resident or newly recruited DCs may have a direct impact on the development of the antigen-specific immune response and thereby, on the outcome of infection. Neutrophils may regulate DC recruitment and/or activation. We will review here recent progress in the field, including those presented during the first international symposium on “Neutrophil in Immunity”, held in Québec, Canada, in June 2012, and discuss how neutrophil regulatory action on DCs may differ depending on the type of invading microorganism and local host factors.
Nr4a1 Is Required for Fasting-Induced Down-Regulation of Pparγ2 in White Adipose Tissue
Authors: Duszka Kalina , Bogner-Strauss Juliane G. , Hackl Hubert , Rieder Dietmar , Neuhold Claudia , Prokesch Andreas , Trajanoski Zlatko , Krogsdam Anne-M.
Published: December 2012

Expression of the nuclear receptor gene, Nur77 (Nr4a1), is induced in white adipose tissue (WAT) in response to β-adrenergic stimulation and fasting. Recently, Nur77 has been shown to play a gene regulatory role in the fasting response of several other major metabolic tissues. Here we investigated the effects of Nur77 on the WAT transcriptome after fasting. For this purpose, we performed gene expression profiling of WAT from wild-type and Nur77−/− mice submitted to prolonged fasting. Results revealed Nur77-dependent changes in expression profiles of 135 transcripts, many involved in insulin signaling, lipid and fatty acid metabolism, and glucose metabolism. Network analysis identified the deregulated genes Pparγ2 and Nur77 as central hubs and closely connected in the network, indicating overlapping biological function. We further assayed the expression level of Pparγ2 in a bigger cohort of fasted mice and found a significant Nur77-dependent down-regulation of Pparγ2 in the wild-type mice (P = 0.021, n = 10). Consistently, the expression of several known Pparγ2 targets, found among the Nur77-regulated genes (i.e. G0s2, Grp81, Fabp4, and Adipoq), were up-regulated in WAT of fasted Nur77−/− mice. Finally, we show with chromatin immunoprecipitation and luciferase assays that the Pparγ2 promoter is a direct target of Nurr-related 77-kDa protein (Nur77)-dependent repressive regulation and that the N-terminal domain of Nur77 is required for this regulation. In conclusion, we present data implicating Nur77 as a mediator of fasting-induced Pparγ2 regulation in WAT.
Androgens Promote Prostate Cancer Cell Growth through Induction of Autophagy
Authors: Shi Yan , Han Jenny J. , Tennakoon Jayantha B. , Mehta Fabiola F. , Merchant Fatima A. , Burns Alan R. , Howe Matthew K. , McDonnell Donald P. , Frigo Daniel E.
Published: December 2012

Androgens regulate both the physiological development of the prostate and the pathology of prostatic diseases. However, the mechanisms by which androgens exert their regulatory activities on these processes are poorly understood. In this study, we have determined that androgens regulate overall cell metabolism and cell growth, in part, by increasing autophagy in prostate cancer cells. Importantly, inhibition of autophagy using either pharmacological or molecular inhibitors significantly abrogated androgen-induced prostate cancer cell growth. Mechanistically, androgen-mediated autophagy appears to promote cell growth by augmenting intracellular lipid accumulation, an effect previously demonstrated to be necessary for prostate cancer cell growth. Further, autophagy and subsequent cell growth is potentiated, in part, by androgen-mediated increases in reactive oxygen species. These findings demonstrate a role for increased fat metabolism and autophagy in prostatic neoplasias and highlight the potential of targeting underexplored metabolic pathways for the development of novel therapeutics.
Comparability of the Black-White Divide in the American Speech Community and the Coloured-White Divide in the Afrikaans Speech Community
Authors: Stell Gerald
Published: December 2012

This article attempts to place the discussion on the relationship between African American and European American vernacular Englishes within a broader context involving another speech community split along ethnic lines, namely South Africa's Afrikaans speakers. It specifically attempts to compare observations on the coloured-white linguistic divide within South Africa's Afrikaans speech community with those made on the black-white linguistic divide in the United States, with the aim of shedding light on the correlation between ethnicity and language variation. The article first presents ethnicity and its social and linguistic correlates, drawing on literature on AA(V)E and South Africa. It then identifies the social and linguistic specificities of the American English and Afrikaans speech communities. After presenting a range of grammatical variables and their comparability across both speech communities, it provides an overview first of the various trends of grammatical variation from a mainly variationist perspective, then of Afrikaans-English code-switching, which is treated as a phenomenon that correlates with grammatical variation. It finally attempts to answer the general question whether the U.S. black-white linguistic divide and the coloured-white linguistic divide in South Africa's Afrikaans speech community can be referred to as complementary in the study of ethnicity and language variation.
Where Are the Moun[ɁƏ]ns in Utah?
Authors: Eddington David , Savage Matthew
Published: December 2012

One stigmatized feature of Utah speech is the “dropped t” in words such as kitten and mountain. We investigated three possible phonetic correlates of “t-dropping” by recording participants from Utah and other Western states reading a document containing several instances of /t/ followed by a syllabic nasal. The first possible correlate, actual deletion of /t/, was uncommon but occurred slightly more often in the mouths of Utahns. The second possible correlate was realizing /t/ as a glottal stop, which was actually done more often by non-Utahns than Utahns (89% versus 81%, resp.). The third correlate, releasing the glottal stop orally rather than nasally (e.g., [khiɁƏn] and [mawɁƏn] vs. [khiɁƏn̩] and [mawɁƏn̩]) is the most likely candidate for “t-dropping” since Utahns did this in 17% of the cases compared to less than 1% in non-Utahns. Logistic regression analysis of the data indicates that age, percentage of life lived in Utah, and gender were strong predictors of oral release; it was used most often by young females who had lived the majority of their life in Utah.
“Tuni’r Ma”: From Nation to “Inter”-Nation
Authors: Baidya Animesh
Published: December 2012

Baidya’s essay explores certain aspects of cultural exchange and the modes of reception and adaptation of any cultural product in the context of popular culture in India, Bangladesh, and Pakistan. The article concentrates on the zone of popular culture of larger Bengal, i.e., the areas in East India including Bangladesh, where Bangla is the official language. Here the history of a popular song, “Tuni’r Ma,” is used to exemplify the holistic understanding of the dynamics involved in the process of cultural reconciliation. The song leads to a discussion of aesthetics and gender theory that explores the conflict between popular and serious culture on the basis of taste. Conventional academic ideas generally link progressive thinking to serious cultural practice. But this essay confronts the hegemonic concept of culture and sheds light on an eclectic area of popular culture that is more prevalent in society. Thus, it might instigate a rational alternative to conventional criticism.
Aryans and the Brahminization of Theory: Identity Politics East and West, Past and Present
Authors: Figueira Dorothy
Published: December 2012

In this essay, Figueira discusses how the Aryan past can be studied as a myth, meaning a form of discourse that can be employed in the construction or the deconstruction of society. In particular, this examination focuses on the discourse concerning the Aryan race as a shared myth in nineteenth-century India and in Germany. Myths concerning the Aryans gave historical value to ancient Indian history, contributing to the ideological concerns of India during the colonial and nationalist periods. They also served the political and ideological interests of Europe: The history of India could be appropriated as a means of expressing nineteenth-century European concern with origins. An examination of the Aryan myth thus addresses a fundamental concern of postcolonial criticism, namely that the West needed to constitute the Orient as its Other in order to constitute itself and its own subjective position. Finally, Figueira examines how analogous notions regarding identity resurface in modern critical theories of ideal readers and spokespersonship. A comparative analysis of representations of the Aryan in India and in the West can shed light on how South Asia is constructed today in global academe. The conclusion, therefore, investigates how Indian racial ideology continues to resonate in current-day identity politics. Understanding such an ideology necessitates a comparative literary evaluation, particularly if such an analysis can unmask the repetition of hegemonic race relations in current “liberatory” theories and pedagogies.
Tell Me Something I Don’t Know
Authors: Beard Michael
Published: December 2012

Beard’s essay contends that specialized journals with limited readerships encounter similar problems. Independent of the subject there are material conditions that limit, shape, or color a journal’s possibilities. These conditions become especially vivid to editors. In the case of journals and book series dealing with the literatures of the Middle East, the constraints are in part political. (Readers bring to the area preexisting commitments and expectations.) In part they are methodological. (Writers trained in Middle East Studies are likely to come to literature from different disciplines other than literary analysis.) In part they are regional. (Contributors usually have specialized in a particular culture or language — Turkish, Persian, or Arabic, in addition to lesser-taught languages like Uighur, Urdu, or Uzbek.) Beard describes his experiences as an editor of two projects: the journal Middle Eastern Literatures and the series “Middle Eastern Literatures in Translation.” In both cases the primary value is generating dialogue between specialists from different backgrounds.
Rereading Ottoman Accounts of Wahhabism as Alternative Narratives: Ahmed Cevdet Paşa’s Historical Survey of the Movement
Authors: Evered Emine Ö.
Published: December 2012

Critical theory enables us to engage with historic power relations of colonizer and colonized, but the inclination to do so should not obfuscate the fact that many narratives that were once in opposition to the empires of the past are now the dominant—and often rewritten— narratives of particular authoritative nation-states. Amid ongoing efforts to author singular metanarratives of the history of the Wahhabi movement of Arabia, alternative histories from the Ottoman perspective are often overlooked or simply dismissed. While the result tends to be the sort of linear history that favors the modern nation-state of Saudi Arabia, it is also a product that omits not only the Ottoman imperial voice but also the many voices and collective memories of those who might be said to have been marginalized and/or victimized by the early Wahhabi movement as it attacked Shiites and others in Karbala and elsewhere. Focusing on the Ottoman histories of Ahmed Cevdet Paşa, Evered’s article summarizes and analyzes the first efforts to depict the movement in Ottoman historiography. In doing so, it also considers how imperial histories may be read today as alternative narratives in the modern nation-state era.
Regulations and Remittances from British Indian Indentured Guianese
Authors: Roopnarine Lomarsh
Published: December 2012

Roopnarine’s article focuses on two themes: the system of remittances and the amount of savings remitted from British Guiana to India during the period of Indian indenture. The article shows that an inadequate registration system as well as poor communication among indentured Indians with their homeland stymied the process of sending remittances. Remittances were left unclaimed in both British Guiana and India. Nevertheless, indentured Indians did remit significant savings from British Guiana, although these savings did not come solely from indentured labor. The article concludes that while a majority of indentured Indians benefited marginally from indentured service, a small number of them took back more savings than what was revealed to the Immigration Department.
Civil Society and Democratic Change in the Arab World: Promises and Impediments
Authors: Zayani Mohamed
Published: December 2012

The advent of civil society in the Arab world, the proliferation of nongovernmental advocacy organizations, and the expansion of civil society activism have been heralded as promising developments with significant implications on the region’s immutable political environment. While noting the vibrancy of civil society, Zayani’s article questions its ability to affect the existing political culture of the region. It argues that the proclivity of civil society activism and associational life to generate political change in the Middle East and North Africa is limited. This is so not so much because the Middle East does not have a strong tradition for supporting civil society or because the concept of civil society is anathema to the region, but because the development of an effective civil society is contingent on a set of political realities, social dispositions, and economic conditions that are missing in the Arab world. In spite of the increasing popularity of civil society activism founded on religious beliefs and the West’s vigorous promotion of associational life as a policy tool to induce political change, the social, political, and legal conditions for a potentially consequential civil society are not fully developed.
Physical gills in diving insects and spiders: theory and experiment
Authors: Seymour Roger S. , Matthews Philip G. D.
Published: December 2012

Insects and spiders rely on gas-filled airways for respiration in air. However, some diving species take a tiny air-store bubble from the surface that acts as a primary O2 source and also as a physical gill to obtain dissolved O2 from the water. After a long history of modelling, recent work with O2-sensitive optodes has tested the models and extended our understanding of physical gill function. Models predict that compressible gas gills can extend dives up to more than eightfold, but this is never reached, because the animals surface long before the bubble is exhausted. Incompressible gas gills are theoretically permanent. However, neither compressible nor incompressible gas gills can support even resting metabolic rate unless the animal is very small, has a low metabolic rate or ventilates the bubble's surface, because the volume of gas required to produce an adequate surface area is too large to permit diving. Diving-bell spiders appear to be the only large aquatic arthropods that can have gas gill surface areas large enough to supply resting metabolic demands in stagnant, oxygenated water, because they suspend a large bubble in a submerged web.
Circular RNAs are abundant, conserved, and associated with ALU repeats
Authors: Jeck William R. , Sorrentino Jessica A. , Wang Kai , Slevin Michael K. , Burd Christin E. , Liu Jinze , Marzluff William F. , Sharpless Norman E.
Published: December 2012

Circular RNAs composed of exonic sequence have been described in a small number of genes. Thought to result from splicing errors, circular RNA species possess no known function. To delineate the universe of endogenous circular RNAs, we performed high-throughput sequencing (RNA-seq) of libraries prepared from ribosome-depleted RNA with or without digestion with the RNA exonuclease, RNase R. We identified >25,000 distinct RNA species in human fibroblasts that contained non-colinear exons (a “backsplice”) and were reproducibly enriched by exonuclease degradation of linear RNA. These RNAs were validated as circular RNA (ecircRNA), rather than linear RNA, and were more stable than associated linear mRNAs in vivo. In some cases, the abundance of circular molecules exceeded that of associated linear mRNA by >10-fold. By conservative estimate, we identified ecircRNAs from 14.4% of actively transcribed genes in human fibroblasts. Application of this method to murine testis RNA identified 69 ecircRNAs in precisely orthologous locations to human circular RNAs. Of note, paralogous kinases HIPK2 and HIPK3 produce abundant ecircRNA from their second exon in both humans and mice. Though HIPK3 circular RNAs contain an AUG translation start, it and other ecircRNAs were not bound to ribosomes. Circular RNAs could be degraded by siRNAs and, therefore, may act as competing endogenous RNAs. Bioinformatic analysis revealed shared features of circularized exons, including long bordering introns that contained complementary ALU repeats. These data show that ecircRNAs are abundant, stable, conserved and nonrandom products of RNA splicing that could be involved in control of gene expression.
Rapid and specific purification of Argonaute-small RNA complexes from crude cell lysates
Authors: Flores-Jasso C. Fabián , Salomon William E. , Zamore Phillip D.
Published: December 2012

Small interfering RNAs (siRNAs) direct Argonaute proteins, the core components of the RNA-induced silencing complex (RISC), to cleave complementary target RNAs. Here, we describe a method to purify active RISC containing a single, unique small RNA guide sequence. We begin by capturing RISC using a complementary 2′-O-methyl oligonucleotide tethered to beads. Unlike other methods that capture RISC but do not allow its recovery, our strategy purifies active, soluble RISC in good yield. The method takes advantage of the finding that RISC partially paired to a target through its siRNA guide dissociates more than 300 times faster than a fully paired siRNA in RISC. We use this strategy to purify fly Ago1- and Ago2-RISC, as well as mouse AGO2-RISC. The method can discriminate among RISCs programmed with different guide strands, making it possible to deplete and recover specific RISC populations. Endogenous microRNA:Argonaute complexes can also be purified from cell lysates. Our method scales readily and takes less than a day to complete.
Role of New Drugs for Management of Atrial Fibrillation
Authors: Hollands James M , Gowan Mollie , Riney Jennifer N , Deal Eli N , Kates Andrew M
Published: December 2012

Objective:

To evaluate the role of newer agents in the management of atrial fibrillation (AF).

Data Sources:

EMBASE and MEDLINE were searched (up to June 2012) combining medication names with atrial fibrillation, humans, clinical trials, and pharmacoeconomic. References of the articles identified and www.clinicaltrials.gov were also reviewed.

Study Selection and Data Extraction:

Studies were limited to the English language with clinical or pharmacoeconomic end points followed by the consensus of 3 authors.

Data Synthesis:

Formulated to reduce some of the adverse effects associated with amiodarone by removing the iodine component, dronedarone has improved clinical outcomes over placebo when used in paroxysmal or persistent AF; however, it is less efficacious than amiodarone. Worse outcomes with dronedarone have been seen in patients with heart failure or permanent AF. It has not been compared to antiarrhythmic agents other than amiodarone, and pharmacoeconomic evaluations are lacking. Dabigatran 150 mg is superior to warfarin in preventing stroke or systemic embolism and has been associated with lower rates of vascular-associated mortality. Although the rates of major bleeding were not significantly different between the 2 agents, gastrointestinal bleeding and myocardial infarction occurred more frequently with dabigatran. Dabigatran appears to have the most pharmacoeconomic benefit over warfarin in patients with a higher risk of stroke. Rivaroxaban is noninferior to warfarin for the prevention of stroke and systemic embolism, with no difference in the rates of major bleeding. Cost-effectiveness studies have not been performed with this agent at this time. In patients with AF who were not suitable candidates for warfarin, apixaban is superior to aspirin in preventing stroke or systemic embolism without increasing the risk for major bleeding. Additionally, apixaban is superior to warfarin in preventing stroke or systemic embolism, results in fewer bleeding events, and is associated with lower mortality. Apixaban is not cost-effective against aspirin when used for a short duration but gains superiority with prolonged use or in patients with higher risks of stroke. Additionally, apixaban appears to offer a pharmacoeconomic advantage over warfarin at no to minimal cost. Each new anticoagulant lacks a reversal agent and an assay to detect the presence of the anticoagulant, as well as long-term data when used in the clinical setting.

Conclusions:

Use of dronedarone should be limited to patients with paroxysmal or persistent AF and should not be used in patients with heart failure or with permanent AF. Newer antithrombotic agents appear to be promising alternatives for the prevention of stroke in patients with AF; however, more data are needed to understand their role.
A Review and Assessment of Drug-Induced Parotitis
Authors: Brooks Krista G , Thompson Dennis F
Published: December 2012

Objective:

To review the current literature on drug-induced parotitis.

Data Sources:

Literature was accessed through MEDLINE/PubMed (1980-May 2012), using the search terms sialadenitis/chemically induced and parotitis/chemically induced. EMBASE (1980-May 2012) was searched using the terms parotitis/diagnosis, sialadenitis/side effect, and parotitis/side effect. International Pharmaceutical Abstracts (1970-May 2012) was searched using the search terms parotitis and sialadenitis. All searches were limited to articles on humans written in English. Inclusion criteria were published letters, case reports, reviews, and clinical trials involving drugs that may be associated with parotitis. Articles pertaining to parotitis induced by iodine-containing drugs were excluded. References of all relevant articles were reviewed for additional citations.

Study Selection and Data Extraction:

Review articles, clinical trials, background data, and case reports of drug-induced parotitis were collected and case reports were assessed for causality.

Data Synthesis:

Parotitis is an uncommon adverse effect; however, signs and symptoms of parotitis have been noted in case reports as an adverse drug reaction related to various medications. Assessing causality of an adverse drug reaction such as parotitis is challenging. To help determine the probability of causality for these events, algorithms such as the Naranjo probability scale have been developed. Eighty-four case reports of drug-induced parotitis from 40 different drugs were reviewed using a modified Naranjo probability scale that included criteria specific for parotitis. Medications that met the criteria for establishing causality included l-asparaginase with 7 case reports, clozapine with 13 case reports, and phenylbutazone with 13 case reports.

Conclusions:

Drug-induced parotitis is a rare adverse drug reaction. Based on the quantitative and qualitative evidence collected from the case reports, medications that are associated with drug-induced parotitis include L-asparaginase, clozapine, and phenylbutazone. Many other drugs have been implicated in the development of parotitis; however, the evidence supporting this association is insufficient to determine causality at this time.
Bioidentical Progesterone Cream for Menopause-Related Vasomotor Symptoms: Is it Effective?
Authors: Whelan Anne Marie , Jurgens Tannis M , Trinacty Melanie
Published: December 2012

OBJECTIVE

To evaluate the efficacy of bioidentical progesterone cream in the treatment of menopause-related vasomotor symptoms.

DATA SOURCES

A systematic search (from time of inception to September 2012) of PubMed, EMBASE, International Pharmaceutical Abstracts, International Journal of Pharmaceutical Compounding, Cochrane, and CINAHL was conducted using the terms progesterone, vasomotor symptoms, night sweats, hot flash or flush, and randomized controlled trials (RCTs). Hand-searching of citations from relevant articles was also performed.

STUDY SELECTION AND DATA EXTRACTION

Articles selected for inclusion described RCTs evaluating the use of bioidentical progesterone cream for the treatment of menopause-related vasomotor symptoms. Studies included were placebo controlled and participants were postmenopausal women experiencing vasomotor symptoms.

DATA SYNTHESIS

Searching identified 3 published RCTs. Only one study, which used a bioidentical progesterone cream specifically compounded for the trial, found that the bioidentical progesterone was more effective than placebo in relieving menopause-related vasomotor symptoms. The 2 studies using manufactured bioidentical progesterone creams found that the creams were no more effective than placebo. Vaginal bleeding and headaches were the most commonly reported adverse effects in the studies.

CONCLUSIONS

Available evidence from RCTs does not support the efficacy of bioidentical progesterone cream for the management of menopause-related vasomotor symptoms. Adverse effects appear to be mild and self-limiting.
Icatibant for the Treatment of Hereditary Angioedema
Authors: Cole Sabrina W , Lundquist Lisa M
Published: December 2012

OBJECTIVE

To review the pharmacology, pharmacokinetics, clinical trials, and safety of icatibant, a recently approved bradykinin B2 receptor antagonist for treatment of acute attacks of hereditary angioedema (HAE).

DATA SOURCES

Articles indexed in MEDLINE (1948-June 2012), International Pharmaceutical Abstracts(1970-May 2012), and Cumulative Index to Nursing and Allied Health Literature (1981-June 2012) were identified using the search terms icatibant, bradykinin B2 receptor antagonist, and hereditary angioedema. Additional references were identified from the reference lists of the articles identified.

STUDY SELECTION AND DATA EXTRACTION

English-language articles were reviewed.

DATA SYNTHESIS

Icatibant was evaluated in 3 Phase 3 clinical trials and found to be a safe and effective option for treatment of acute HAE. Icatibant was compared to placebo in 2 clinical trials (FAST-1 and FAST-3) and to tranexamic acid in the FAST-2 trial. Patients receiving icatibant in FAST-1 did not experience a significant improvement in median time to clinically significant relief of the index symptom (p = 0.14), whereas patients receiving icatibant in FAST-3 experienced a significant improvement in median time to at least 50% reduction in symptom severity (p < 0.001). When icatibant was compared to tranexamic acid in FAST-2, the median time to clinically significant relief of the index symptom was shorter for patients receiving icatibant (p < 0.001). The most common adverse events associated with the administration of icatibant were injection-site reactions, which were mild to moderate and transient. These data suggest that icatibant is a safe and effective treatment for acute attacks of HAE. Although direct comparisons of recently approved alternatives for treatment of acute attacks are lacking, there are administration advantages of icatibant over other agents. Additionally, the cost of icatibant is comparable to that of the C1 esterase inhibitor Berinert and less expensive than ecallantide.

CONCLUSIONS

Available efficacy data support that icatibant should be considered a safe and effective treatment for acute attacks of HAE. Additionally, limited treatment options for this rare condition, ease of administration, and comparable cost profile support its consideration for formulary inclusion.