bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute Changes in Pulmonary Function Following Microinstillation Inhalation Exposure to Soman in Nonatropenized Guinea Pigs
Authors: Perkins Michael W. , Pierre Zdenka , Rezk Peter , Song Jian , Oguntayo Samuel , Sciuto Alfred M. , Doctor Bhupendra P. , Nambiar Madhusoodana P.
Published: April 2011

Barometric whole-body plethysmography (WBP) was used to examine pulmonary functions at 4 and 24 hours postexposure to soman (GD) in guinea pigs without therapeutics to improve survival. Endotracheal aerosolization by microinstillation was used to administer GD (280, 561, and 841 mg/m3) or saline to anesthetized guinea pigs. Significant increases in respiratory frequency (RF), tidal volume (TV), and minute volume (MV) were observed with 841 mg/m3 GD at 4 hours and that were reduced at 24 hours postexposure. A dose-dependent increase in peak inspiration flow and peak expiration flow was present at 4-hour post-GD exposure that was reduced at 24 hours. Time of inspiration and expiration were decreased in all doses of GD exposure at 4 and 24 hours, with significant inhibition at 841 mg/m3. End-expiratory pause (EEP) increased at 280 and 561 mg/m3, but decreased in animals exposed 841 mg/m3 at 24 hours postexposure. Pseudo-lung resistance (Penh) and pause followed similar patterns and increased at 4 hours, but decreased at 24 hours postexposure to 841 mg/m3 of GD compared to control. These studies indicate GD exposure induces dose-dependent changes in pulmonary function that are significant at 841 mg/m3 at 4 hours and remains 24 hours postexposure. Furthermore, at 4 hours, GD induces bronchoconstriction possibly due to copious airway secretion and ongoing lung injury in addition to cholinergic effects, while at 24 hours GD induces bronchodilation a possible consequence of initial compensatory mechanisms.
Longer Time Interval Between Carotid Cross-Clamping and Shunting Is Associated With Increased 30-Day Stroke and Death Rate
Authors: Wisman P.P. , Tutein Nolthenius R.P. , Tromp S.C. , Kelder J.C. , de Vries Jean-Paul P. M.
Published: April 2011

Background: The benefit of carotid endarterectomy (CEA) in patients with a significant (>70%) (a)symptomatic stenosis has been proven thoroughly in major trials. It is unknown whether, after cross-clamping the carotid artery, the time interval between determination that a shunt is needed and the actual functioning of the shunt, defined as the need for shunt-to-shunt time (NST), influences 30-day morbidity and mortality rate after CEA. Methods: Experienced vascular surgeons performed 851 CEAs with a selective shunting protocol based on perioperative transcranial Doppler measurement and electroencephalographic findings, and data were analyzed retrospectively. The study included 156 shunted patients. Results: Longer NST was associated with an increase in the 30-day stroke/death rate. A binary logistic regression model was used to determine a 2-tailed P value of .004 and an odds ratio of 1.5/min increase of the NST. There was no influence on stroke-death rate of gender, age, symptomatic or asymptomatic stenosis, the use of a patch or not, or the number of periprocedural microembolic signals. Conclusion: If CEA is performed with a selective shunting protocol, a longer NST increases the 30-day stroke/death rate. These results support a strong recommendation that shunt placement should be as quick as possible.
Stent-Assisted Coil Embolization of an Intraparenchymal Renal Artery Aneurysm in a Patient With Neurofibromatosis
Authors: Somarouthu Bhanusupriya , Rabinov James , Waichi Wong  , Kalva Sanjeeva P.
Published: April 2011

True renal artery aneurysms are rare. They are generally asymptomatic, however, a few may present with hypertension, rupture, or renal dysfunction secondary to distal embolization. Indications for intervention include aneurysm of ≥2.0 cm in diameter, renovascular hypertension, enlarging aneurysm, associated dissection /rupture, and aneurysms in women of child-bearing age/ pregnancy. Endovascular therapy through coil embolization or stent graft exclusion is the recommended management. Coil embolization of the first and second order branch aneurysms is often associated with distal parenchymal loss and current stent graft technology prohibits use of these endoprostheses in the branch renal arteries. In this report, we describe successful stent-assisted coil embolization of an intraparenchymal aneurysm while preserving the distal parenchyma in a young woman with Neurofibromatosis type 1.
Successful Total Robotic-Assisted Aortobifemoral Bypass for Treatment of Complicated Aortoiliac Occlusive Disease
Authors: Lin Judith C. , Kaul Sanjeev A. , Rogers Craig G.
Published: April 2011

Laparoscopic aortobifemoral bypass (AFB) for aortoiliac occlusive disease (AIOD) is a durable, minimally invasive procedure with comparable long-term outcomes to conventional open AFB. However, laparoscopic AFB requires advance training in laparoscopy with prolong learning curve to accomplish infrarenal aortic dissection and vascular reconstruction to minimize aortic clamp time and leg ischemia time. We describe another minimally invasive technique of total robotic-assisted AFB for extensive, complicated AIOD in 3 patients who are not endovascular candidate or have failed endoluminal approach previously.
Health Care Disparity in the Care of the Vascular Patient
Authors: Kirksey Lee
Published: April 2011

Peripheral vascular care continues to mature into a well-developed multidisciplinary subspecialty. Continued growth as a collaborative subspecialty will require delivering the highest quality medical care to all Americans. US census projections predict that greater than one half of all American citizens will identify themselves as ethnic or racial minorities by 2050. Evolving research has established significant health care disparity, or preventable differences in disease incidence and vascular procedure outcomes associated with socioeconomic, gender, language, geographic, racial, and ethnic variables. As a necessary step in the evolution of vascular care, practitioners, societies, and vascular departments should begin to adopt proven practices that enhance our ability to deliver equal care to an increasingly diverse American population.
A New Hope for Rank and Yank
Authors: Mulligan Jamie R. , Bull Schaefer Rebecca A.
Published: April 2011

Using simulations to study the effects of performance appraisal format on workforce performance potential, the authors explore modifications of force distributional rating systems that terminate poor performers each evaluation period. Findings suggest that systems with probationary periods before termination may realize some of the gains in workforce performance potential that traditional “rank and yank” systems pose, while also having the potential to increase fairness perceptions and, in turn, reduce voluntary turnover. Despite perceptions in practice, results show that temporary use of “rank and yank” may do more harm than good in that levels of workforce performance potential may not be maintained.
Moderate Exercise Improves Immunity and Decreases Illness Rates
Authors: Nieman David C.
Published: April 2011

Moderate exercise training causes favorable perturbations in immunity and a reduction in incidence of upper-respiratory illness (URI). During each bout of moderate exercise, an enhanced recirculation of immunoglobulins, neutrophils, and natural killer cells occurs that persists for up to 3 hours postexercise. This exercise-induced surge in immune cells from the innate immune system is transient but improves overall surveillance against pathogens. As moderate exercise continues on a near-daily basis for 12 to 15 weeks, the number of symptom days with URI is decreased 25% to 50% compared with randomized sedentary controls. Epidemiological and animal studies support this inverse relationship between URI risk and increased physical activity. Recent evidence indicates that maintaining leanness and a physically active lifestyle during adulthood reduces systemic inflammation, an underlying factor in multiple chronic diseases. The anti-inflammatory influence of near-daily physical activity in lowering C-reactive protein, total blood leukocytes, interleukin-6, and other inflammatory cytokines may play a key role in lowering risk of cardiovascular disease, certain types of cancer, type 2 diabetes, sarcopenia, and dementia.
Using impedance cardiography with postural change to stratify patients with hypertension
Authors: DeMarzo Arthur P.
Published: April 2011

Background: Early detection of cardiovascular disease in patients with hypertension could initiate appropriate treatment to control blood pressure and prevent the progression of cardiovascular disease.

Objective: The goal of this study was to show how impedance cardiography waveform analysis with postural change can be used to detect subclinical cardiovascular disease in patients with high blood pressure.

Methods: Patients with high blood pressure had impedance cardiography data obtained in two positions, standing upright and supine.

Results: In 50 adults, impedance cardiography indicated that all patients had abnormal data, with 44 (88%) having multiple abnormalities. Impedance cardiography showed 32 (64%) had ventricular dysfunction, 48 (96%) had vascular load abnormalities, 34 (68%) had hemodynamic abnormalities, 2 (4%) had hypovolemia, and 3 (6%) had hypervolemia.

Conclusions: Hypertensive patients have diverse cardiovascular abnormalities that can be quantified by impedance cardiography. By stratifying patients with ventricular, vascular, and hemodynamic abnormalities, treatment could be customized based on the abnormal underlying mechanisms with the potential to rapidly control blood pressure, prevent progression of cardiovascular disease, and possibly reverse remodeling.
Examination and Treatment of Cuboid Syndrome
Authors: Durall Chris J.
Published: April 2011

Context: Cuboid syndrome is thought to be a common source of lateral midfoot pain in athletes.

Evidence Acquisition: A Medline search was performed via PubMed (through June 2010) using the search terms cuboid, syndrome, subluxed, locked, fault, dropped, peroneal, lateral, plantar, and neuritis with the Boolean term AND in all possible combinations. Retrieved articles were hand searched for additional relevant references.

Results: Cuboid syndrome is thought to arise from subtle disruption of the arthrokinematics or structural congruity of the calcaneocuboid joint, although the precise pathomechanic mechanism has not been elucidated. Fibroadipose synovial folds (or labra) within the calcaneocuboid joint may play a role in the cause of cuboid syndrome, but this is highly speculative. The symptoms of cuboid syndrome resemble those of a ligament sprain. Currently, there are no definitive diagnostic tests for this condition. Case reports suggest that cuboid syndrome often responds favorably to manipulation and/or external support.

Conclusions: Evidence-based guidelines regarding cuboid syndrome are lacking. Consequently, the diagnosis of cuboid syndrome is often based on a constellation of signs and symptoms and a high index of suspicion. Unless contraindicated, manipulation of the cuboid should be considered as an initial treatment.
A CK2-dependent mechanism for activation of the JAK-STAT signaling pathway
Authors: Zheng Ying , Qin Hongwei , Frank Stuart J. , Deng Luqin , Litchfield David W. , Tefferi Ayalew , Pardanani Animesh , Lin Fang-Tsyr , Li Jingzhi , Sha Bingdong , Benveniste Etty N.
Published: April 2011

JAK-STAT signaling is involved in the regulation of cell survival, proliferation, and differentiation. JAK tyrosine kinases can be transiently activated by cytokines or growth factors in normal cells, whereas they become constitutively activated as a result of mutations that affect their function in tumors. Specifically, the JAK2V617F mutation is present in the majority of patients with myeloproliferative disorders (MPDs) and is implicated in the pathogenesis of these diseases. In the present study, we report that the kinase CK2 is a novel interaction partner of JAKs and is essential for JAK-STAT activation. We demonstrate that cytokine-induced activation of JAKs and STATs and the expression of suppressor of cytokine signaling 3 (SOCS-3), a downstream target, are inhibited by CK2 small interfering RNAs or pharmacologic inhibitors. Endogenous CK2 is associated with JAK2 and JAK1 and phosphorylates JAK2 in vitro. To extend these findings, we demonstrate that CK2 interacts with JAK2V617F and that CK2 inhibitors suppress JAK2V617F autophosphorylation and downstream signaling in HEL92.1.7 cells (HEL) and primary cells from polycythemia vera (PV) patients. Furthermore, CK2 inhibitors potently induce apoptosis of HEL cells and PV cells. Our data provide evidence for novel cross-talk between CK2 and JAK-STAT signaling, with implications for therapeutic intervention in JAK2V617F-positive MPDs.
Sphingosine kinase-1 and sphingosine 1-phosphate receptor 2 mediate Bcr-Abl1 stability and drug resistance by modulation of protein phosphatase 2A
Authors: Salas Arelis , Ponnusamy Suriyan , Senkal Can E. , Meyers-Needham Marisa , Selvam Shanmugam Panneer , Saddoughi Sahar A. , Apohan Elif , Sentelle R. David , Smith Charles , Gault Christopher R. , Obeid Lina M. , El-Shewy Hesham M. , Oaks Joshua , Santhanam Ramasamy , Marcucci Guido , Baran Yusuf , Mahajan Sandeep , Fernandes Daniel , Stuart Robert , Perrotti Danilo , Ogretmen Besim
Published: April 2011

The mechanisms by which sphingosine kinase-1 (SK-1)/sphingosine 1-phosphate (S1P) activation contributes to imatinib resistance in chronic myeloid leukemia (CML) are unknown. We show herein that increased SK-1/S1P enhances Bcr-Abl1 protein stability, through inhibition of its proteasomal degradation in imatinib-resistant K562/IMA-3 and LAMA-4/IMA human CML cells. In fact, Bcr-Abl1 stability was enhanced by ectopic SK-1 expression. Conversely, siRNA-mediated SK-1 knockdown in K562/IMA-3 cells, or its genetic loss in SK-1−/− MEFs, significantly reduced Bcr-Abl1 stability. Regulation of Bcr-Abl1 by SK-1/S1P was dependent on S1P receptor 2 (S1P2) signaling, which prevented Bcr-Abl1 dephosphorylation, and degradation via inhibition of PP2A. Molecular or pharmacologic interference with SK-1/S1P2 restored PP2A-dependent Bcr-Abl1 dephosphorylation, and enhanced imatinib- or nilotinib-induced growth inhibition in primary CD34+ mononuclear cells obtained from chronic phase and blast crisis CML patients, K562/IMA-3 or LAMA4/IMA cells, and 32Dcl3 murine progenitor cells, expressing the wild-type or mutant (Y253H or T315I) Bcr-Abl1 in situ. Accordingly, impaired SK-1/S1P2 signaling enhanced the growth-inhibitory effects of nilotinib against 32D/T315I-Bcr-Abl1–derived mouse allografts. Since SK-1/S1P/S1P2 signaling regulates Bcr-Abl1 stability via modulation of PP2A, inhibition of SK-1/S1P2 axis represents a novel approach to target wild-type- or mutant-Bcr–Abl1 thereby overcoming drug resistance.
Dexamethasone and lenalidomide have distinct functional effects on erythropoiesis
Authors: Narla Anupama , Dutt Shilpee , McAuley J. Randall , Al-Shahrour Fatima , Hurst Slater , McConkey Marie , Neuberg Donna , Ebert Benjamin L.
Published: April 2011

Corticosteroids and lenalidomide decrease red blood cell transfusion dependence in patients with Diamond-Blackfan anemia (DBA) and myelodysplastic syndrome (MDS), respectively. We explored the effects of dexamethasone and lenalidomide, individually and in combination, on the differentiation of primary human bone marrow progenitor cells in vitro. Both agents promote erythropoiesis, increasing the absolute number of erythroid cells produced from normal CD34+ cells and from CD34+ cells with the types of ribosome dysfunction found in DBA and del(5q) MDS. However, the drugs had distinct effects on the production of erythroid progenitor colonies; dexamethasone selectively increased the number of burst-forming units-erythroid (BFU-E), whereas lenalidomide specifically increased colony-forming unit-erythroid (CFU-E). Use of the drugs in combination demonstrated that their effects are not redundant. In addition, dexamethasone and lenalidomide induced distinct gene-expression profiles. In coculture experiments, we examined the role of the microenvironment in response to both drugs and found that the presence of macrophages, the central cells in erythroblastic islands, accentuated the effects of both agents. Our findings indicate that dexamethasone and lenalidomide promote different stages of erythropoiesis and support the potential clinical utility of combination therapy for patients with bone marrow failure.
Serum hepcidin: reference ranges and biochemical correlates in the general population
Authors: Galesloot Tessel E. , Vermeulen Sita H. , Geurts-Moespot Anneke J. , Klaver Siem M. , Kroot Joyce J. , van Tienoven Dorlene , Wetzels Jack F. M. , Kiemeney Lambertus A. L. M. , Sweep Fred C. , den Heijer Martin , Swinkels Dorine W.
Published: April 2011

To date, concentrations of the promising biomarker hepcidin have only been assessed in serum of relatively small series of healthy volunteers and patients. We assessed age- and sex-stratified reference ranges of serum hepcidin concentration in a selected reference set and performed regression analyses to study associations between hepcidin and (biochemical) variables in a large, well-phenotyped sample of the general population (n = 2998). All participants filled out a questionnaire on lifestyle, health status, and medical history. Serum measurements of iron parameters, liver enzyme alanine aminotransferase, creatinine and C-reactive protein were available. Serum hepcidin concentrations were lower for premenopausal than for postmenopausal women (median, 4.1nM vs 8.5nM, respectively). Hepcidin concentrations in men were constant over age (median, 7.8nM). Serum hepcidin was strongly associated with serum ferritin in men and women: β-coefficient of log-transformed variables (95% confidence interval): 0.78 (0.74-0.82) and 0.83 (0.78-0.88), respectively. Additional significant, though less strong, associations were observed for C-reactive protein and total iron binding capacity in men and for total iron binding capacity, alanine aminotransferase, and glomerular filtration rate in women. Our study provides age- and sex-specific reference ranges of serum hepcidin concentration and indicates ferritin as the primary correlate of serum hepcidin concentration.
The testosterone-dependent and independent transcriptional networks in the hypothalamus of Gpr54 and Kiss1 knockout male mice are not fully equivalent
Authors: Prentice Leah M , d'Anglemont de Tassigny Xavier , McKinney Steven , Ruiz de Algara Teresa , Yap Damian , Turashvili Gulisa , Poon Steven , Sutcliffe Margaret , Allard Pat , Burleigh Angela , Fee John , Huntsman David G , Colledge William H , Aparicio Samuel AJ
Published: April 2011

Background

Humans and mice with loss of function mutations in GPR54 (KISS1R) or kisspeptin do not progress through puberty, caused by a failure to release GnRH. The transcriptional networks regulated by these proteins in the hypothalamus have yet to be explored by genome-wide methods.

Results

We show here, using 1 million exon mouse arrays (Exon 1.0 Affymetrix) and quantitative polymerase chain reaction (QPCR) validation to analyse microdissected hypothalamic tissue from Gpr54 and Kiss1 knockout mice, the extent of transcriptional regulation in the hypothalamus. The sensitivity to detect important transcript differences in microdissected RNA was confirmed by the observation of counter-regulation of Kiss1 expression in Gpr54 knockouts and confirmed by immunohistochemistry (IHC). Since Gpr54 and Kiss1 knockout animals are effectively pre-pubertal with low testosterone (T) levels, we also determined which of the validated transcripts were T-responsive and which varied according to genotype alone. We observed four types of transcriptional regulation (i) genotype only dependent regulation, (ii) T only dependent regulation, (iii) genotype and T-dependent regulation with interaction between these variables, (iv) genotype and T-dependent regulation with no interaction between these variables. The results implicate for the first time several transcription factors (e.g. Npas4, Esr2), proteases (Klk1b22), and the orphan 10-transmembrane transporter TMEM144 in the biology of GPR54/kisspeptin function in the hypothalamus. We show for the neuronal activity regulated transcription factor NPAS4, that distinct protein over-expression is seen in the hypothalamus and hippocampus in Gpr54 knockout mice. This links for the first time the hypothalamic-gonadal axis with this important regulator of inhibitory synapse formation. Similarly we confirm TMEM144 up-regulation in the hypothalamus by RNA in situ hybridization and western blot.

Conclusions

Taken together, global transcriptional profiling shows that loss of GPR54 and kisspeptin are not fully equivalent in the mouse hypothalamus.
DX5+NKT cells display phenotypical and functional differences between spleen and liver as well as NK1.1-Balb/c and NK1.1+ C57Bl/6 mice
Authors: Werner Jens M , Busl Elisabeth , Farkas Stefan A , Schlitt Hans J , Geissler Edward K , Hornung Matthias
Published: April 2011

Background

Natural killer T cells represent a linkage between innate and adaptive immunity. They are a heterogeneous population of specialized T lymphocytes composed of different subsets. DX5+NKT cells are characterized by expression of the NK cell marker DX5 in the context of CD3. However, little is known about the phenotype and functional capacity of this unique cell population. Therefore, we investigated the expression of several T cell and NK cell markers, as well as functional parameters in spleen and liver subsets of DX5+NKT cells in NK1.1-Balb/c mice and compared our findings to NK1.1+C57Bl/6 mice.

Results

In the spleen 34% of DX5+NKT cells expressed CD62L and they up-regulated the functional receptors CD154 as well as CD178 upon activation. In contrast, only a few liver DX5+NKT cells expressed CD62L, and they did not up-regulate CD154 upon activation. A further difference between spleen and liver subsets was observed in cytokine production. Spleen DX5+NKT cells produced more Th1 cytokines including IL-2, IFN-γ and TNF-α, while liver DX5+NKT cells secreted more Th2 cytokines (e.g. IL-4) and even the Th17 cytokine, IL-17a. Furthermore, we found inter-strain differences. In NK1.1+C57Bl/6 mice DX5+NKT cells represented a distinct T cell population expressing less CD4 and more CD8. Accordingly, these cells showed a CD178 and Th2-type functional capacity upon activation.

Conclusion

These results show that DX5+NKT cells are a heterogeneous population, depending on the dedicated organ and mouse strain, that has diverse functional capacity.
Gene expression analysis of flax seed development
Authors: Venglat Prakash , Xiang Daoquan , Qiu Shuqing , Stone Sandra L , Tibiche Chabane , Cram Dustin , Alting-Mees Michelle , Nowak Jacek , Cloutier Sylvie , Deyholos Michael , Bekkaoui Faouzi , Sharpe Andrew , Wang Edwin , Rowland Gordon , Selvaraj Gopalan , Datla Raju
Published: April 2011

Background

Flax, Linum usitatissimum L., is an important crop whose seed oil and stem fiber have multiple industrial applications. Flax seeds are also well-known for their nutritional attributes, viz., omega-3 fatty acids in the oil and lignans and mucilage from the seed coat. In spite of the importance of this crop, there are few molecular resources that can be utilized toward improving seed traits. Here, we describe flax embryo and seed development and generation of comprehensive genomic resources for the flax seed.

Results

We describe a large-scale generation and analysis of expressed sequences in various tissues. Collectively, the 13 libraries we have used provide a broad representation of genes active in developing embryos (globular, heart, torpedo, cotyledon and mature stages) seed coats (globular and torpedo stages) and endosperm (pooled globular to torpedo stages) and genes expressed in flowers, etiolated seedlings, leaves, and stem tissue. A total of 261,272 expressed sequence tags (EST) (GenBank accessions LIBEST_026995 to LIBEST_027011) were generated. These EST libraries included transcription factor genes that are typically expressed at low levels, indicating that the depth is adequate for in silico expression analysis. Assembly of the ESTs resulted in 30,640 unigenes and 82% of these could be identified on the basis of homology to known and hypothetical genes from other plants. When compared with fully sequenced plant genomes, the flax unigenes resembled poplar and castor bean more than grape, sorghum, rice or Arabidopsis. Nearly one-fifth of these (5,152) had no homologs in sequences reported for any organism, suggesting that this category represents genes that are likely unique to flax. Digital analyses revealed gene expression dynamics for the biosynthesis of a number of important seed constituents during seed development.

Conclusions

We have developed a foundational database of expressed sequences and collection of plasmid clones that comprise even low-expressed genes such as those encoding transcription factors. This has allowed us to delineate the spatio-temporal aspects of gene expression underlying the biosynthesis of a number of important seed constituents in flax. Flax belongs to a taxonomic group of diverse plants and the large sequence database will allow for evolutionary studies as well.
Evaluating the health and economic impact of osteoarthritis pain in the workforce: results from the National Health and Wellness Survey
Authors: DiBonaventura Marco daCosta , Gupta Shaloo , McDonald Margaret , Sadosky Alesia
Published: April 2011

Background

There has been increasing recognition that osteoarthritis (OA) affects younger individuals who are still participants in the workforce, but there are only limited data on the contribution of OA pain to work productivity and other outcomes in an employed population. This study evaluated the impact of OA pain on healthcare resource utilization, productivity and costs in employed individuals.

Methods

Data were derived from the 2009 National Health and Wellness Survey. Univariable and multivariable analyses were used to characterize employed individuals (full-time, part-time, or self-employed) ≥20 years of age who were diagnosed with OA and had arthritis pain in the past month relative to employed individuals not diagnosed with OA or not experiencing arthritis pain in the past month. Work productivity was assessed using the Work Productivity and Activity Impairment (WPAI) questionnaire; health status was assessed using the physical (PCS) and mental component summary (MCS) scores from the SF-12v2 Health Survey and SF-6D health utilities; and healthcare utilization was evaluated by type and number of resources within the past 6 months. Direct and indirect costs were estimated and compared between the two cohorts.

Results

Individuals with OA pain were less likely to be employed. Relative to workers without OA pain (n = 37,599), the OA pain cohort (n = 2,173) was significantly older (mean age 52.1 ± 11.5 years vs 41.4 ± 13.2 years; P < 0.0001) and with a greater proportion of females (58.2% vs 45.9%; P < 0.0001). OA pain resulted in greater work impairment than among workers without OA pain (34.4% versus 17.8%; P < 0.0001), and was primarily due to presenteeism (impaired activity while at work). Health status, assessed both by the SF-12v2 and the SF-6D was significantly poorer among workers with OA pain (P < 0.0001), and healthcare resource utilization was significantly higher (P < 0.0001) than workers without OA pain. Total costs were higher in the OA pain cohort ($15,047 versus $8,175; P < 0.0001), driven by indirect costs that accounted for approximately 75% of total costs.

Conclusions

A substantial proportion of workers suffer from OA pain. After controlling for confounders, the impact of OA pain was significant, resulting in lower productivity and higher costs.
Human saliva as a source of anti-malarial antibodies to examine population exposure to Plasmodium falciparum
Authors: Estévez Patricia Tabernero , Satoguina Judith , Nwakanma Davis C , West Sheila , Conway David J , Drakeley Chris J
Published: April 2011

Background

Antibody responses to malaria antigens reflect exposure to parasites, and seroprevalence correlates with malaria transmission intensity. Antibodies are routinely measured in sera or on dried blood spots but a non-invasive method would provide extra utility in sampling general populations. Saliva is already in use in the detection of plasma-derived IgM and IgG to viral infections. In this study, antibodies to Plasmodium falciparum merozoite antigens were compared between blood and saliva samples from the same individuals in unlinked surveys conducted in Tanzania and The Gambia.

Methods

In Tanzania, 53 individuals provided paired fingerprick blood and saliva sample using two commercially available sampling devices. In the Gambia, archived plasma and saliva samples collected from 200 children in the Farafenni area in a cross-sectional survey were analyzed.

IgG antibodies against P. falciparum antigens, Merozoite Surface Protein-1 (MSP-119) and Apical membrane Antigen (AMA-1) were measured by ELISA in paired saliva and blood samples from both sites. Antibody levels were compared as continuous optical density (OD) values and by sero-positivity.

Results

Significant correlations between saliva and plasma antibody levels were seen in Tanzania for both antigens, AMA-1(r2 range 0.93 to 0.89, p < 0.001) and MSP-119 (r2 range 0.93 to 0.75, p < 0.001), with a weaker correlation for results from The Gambia (r2range 0.64 to 0.63, p < 0.01). When assessed as seropositivity and compared with plasma, sensitivity and specificity were good with saliva antibody levels to both AMA-1 and MSP-119 (sensitivity range 64-77% and specificity range 91-100% & 47-67% and 90-97% respectively) over the different sample sets.

Conclusions

These data demonstrate anti-malarial antibodies can be detected in saliva and correlate strongly with levels in plasma. This non-invasive relatively simple collection method will be potentially useful for general population surveys, and particularly in migratory populations or those with infrequent contact with health services or opposed to blood withdrawal. Further studies will be needed to optimize collection methods, standardize volumes and content and develop controls.
Coverage of intermittent prevention treatment with sulphadoxine-pyrimethamine among pregnant women and congenital malaria in Côte d'Ivoire
Authors: Vanga-Bosson Henriette A , Coffie Patrick A , Kanhon Serge , Sloan Caroline , Kouakou Firmin , Eholie Serge P , Kone Moussa , Dabis François , Menan Hervé , Ekouevi Didier K
Published: April 2011

Background

The World Health Organization (WHO) recommends using insecticide-treated mosquito nets (ITNs) and intermittent preventive treatment with sulphadoxine-pyrimethamine (IPT-SP) to prevent malaria in sub-Saharan Africa. Data on IPT-SP coverage and factors associated with placental malaria parasitaemia and low birth weight (LBW) are scarce in Côte d'Ivoire.

Methods

A multicentre, cross-sectional survey was conducted in Côte d'Ivoire from March to September 2008 at six urban and semi-urban antenatal clinics. Standardized forms were used to collect the demographic information and medical histories of women and their offspring. IPT-SP coverage (≥2 doses) as well as placental and congenital malaria prevalence parasitaemia were estimated. Regression logistics were used to study factors associated with placental malaria and LBW (birth weight of alive babies < 2,500 grams).

Results

Overall, 2,044 women with a median age of 24 years were included in this study. Among them 1017 (49.8%) received ≥2 doses of IPT-SP and 694 (34.0%) received one dose. A total of 99 mothers (4.8%) had placental malaria, and of them, four cases of congenital malaria were diagnosed. Factors that protected from maternal placental malaria parasitaemia were the use of one dose (adjusted odds ratio (aOR), 0.32; 95%CI: 0.19-0.55) or ≥2 doses IPT-SP (aOR: 0.18; 95%CI: 0.10-0.32); the use of ITNs (aOR: 0.47; 95%CI: 0.27-0.82). LBW was associated with primigravidity and placental malaria parasitaemia.

Conclusion

IPT-SP decreases the rate of placental malaria parasitaemia and has a strong dose effect. Despite relatively successful IPT-SP coverage in Côte d'Ivoire, substantial commitments from national authorities are urgently required for such public health campaigns. Strategies, such as providing IPT-SP free of charge and directly observing treatment, should be implemented to increase the use of IPT-SP as well as other prophylactic methods.
Trust and the regulation of pharmaceuticals: South Asia in a globalised world
Authors: Brhlikova Petra , Harper Ian , Jeffery Roger , Rawal Nabin , Subedi Madhusudhan , Santhosh MR
Published: April 2011

Background

Building appropriate levels of trust in pharmaceuticals is a painstaking and challenging task, involving participants from different spheres of life, including producers, distributors, retailers, prescribers, patients and the mass media. Increasingly, however, trust is not just a national matter, but involves cross-border flows of knowledge, threats and promises.

Methods

Data for this paper comes from the project 'Tracing Pharmaceuticals in South Asia', which used ethnographic fieldwork and qualitative interviews to compared the trajectories of three pharmaceuticals (Rifampicin, Oxytocin and Fluoxetine) from producer to patient in three sites (north India, West Bengal and Nepal) between 2005-08.

Results

We argue that issues of trust are crucial in reducing the likelihood of appropriate use of medicines. Unlike earlier discussions of trust, we suggest that trust contexts beyond the patient-practitioner relationship are important. We illustrate these arguments through three case studies: (i) a conflict over ethics in Nepal, involving a suggested revised ethical code for retailers, medical representatives, producers and prescribers; (ii) disputes over counterfeit, fake, substandard and spurious medicines, and quality standards in Indian generic companies, looking particularly at the role played by the US FDA; and (iii) the implications of lack of trust in the DOTS programmes in India and Nepal for the relationships among patients, government and the private sector.

Conclusions

We conclude that the building of trust is a necessary but always vulnerable and contingent process. While it might be desirable to outline steps that can be taken to build trust, the range of conflicting interests in the pharmaceutical field make feasible solutions hard to implement.
Detection and differentiation of Borrelia burgdorferi sensu lato in ticks collected from sheep and cattle in China
Authors: Niu Qingli , Guan Guiquan , Yang Jifei , Fu Yuguang , Xu Zongke , Li Youquan , Ma Miling , Liu Zhijie , Liu Junlong , Liu Aihong , Ren Qiaoyun , Jorgensen Wayne , Luo Jianxun , Yin Hong
Published: April 2011

Background

Lyme disease caused by Borrelia burgdorferi sensu lato complex is an important endemic zoonosis whose distribution is closely related to the main ixodid tick vectors. In China, isolated cases of Lyme disease infection of humans have been reported in 29 provinces. Ticks, especially ixodid ticks are abundant and a wide arrange of Borrelia natural reservoirs are present. In this study, we developed a reverse line blot (RLB) to identify Borrelia spp. in ticks collected from sheep and cattle in 7 Provinces covering the main extensive livestock regions in China.

Results

Four species-specific RLB oligonucleotide probes were deduced from the spacer region between the 5S-23S rRNA gene, along with an oligonucleotide probe which was common to all. The species specific probes were shown to discriminate between four genomic groups of B. burgdorferi sensu lato i.e. B. burgdorferi sensu stricto, B. garinii, B. afzelii, and B. valaisiana, and to bind only to their respective target sequences, with no cross reaction to non target DNA. Furthermore, the RLB could detect between 0.1 pg and 1 pg of Borrelia DNA.

A total of 723 tick samples (Haemaphysalis, Boophilus, Rhipicephalus and Dermacentor) from sheep and cattle were examined with RLB, and a subset of 667 corresponding samples were examined with PCR as a comparison. The overall infection rate detected with RLB was higher than that of the PCR test.

The infection rate of B. burgdoreri sensu stricto was 40% in south areas; while the B. garinii infection rate was 40% in north areas. The highest detection rates of B. afzelii and B. valaisiana were 28% and 22%, respectively. Mixed infections were also found in 7% of the ticks analyzed, mainly in the North. The proportion of B. garinii genotype in ticks was overall highest at 34% in the whole investigation area.

Conclusion

In this study, the RLB assay was used to detect B. burgdorferi sensu lato in ticks collected from sheep and cattle in China. The results showed that B. burdorferi senso stricto and B. afzelii were mainly distributed in the South; while B. garinii and B. valaisiana were dominant in the North. Borrelia spirochaetes were detected in Rhipicephalus spp for the first time. It is suggested that the Rhipicephalus spps might play a role in transmitting Borrelia spirochaetes.
KBWS: an EMBOSS associated package for accessing bioinformatics web services
Authors: Oshita Kazuki , Arakawa Kazuharu , Tomita Masaru
Published: April 2011

The availability of bioinformatics web-based services is rapidly proliferating, for their interoperability and ease of use. The next challenge is in the integration of these services in the form of workflows, and several projects are already underway, standardizing the syntax, semantics, and user interfaces. In order to deploy the advantages of web services with locally installed tools, here we describe a collection of proxy client tools for 42 major bioinformatics web services in the form of European Molecular Biology Open Software Suite (EMBOSS) UNIX command-line tools. EMBOSS provides sophisticated means for discoverability and interoperability for hundreds of tools, and our package, named the Keio Bioinformatics Web Service (KBWS), adds functionalities of local and multiple alignment of sequences, phylogenetic analyses, and prediction of cellular localization of proteins and RNA secondary structures. This software implemented in C is available under GPL from http://www.g-language.org/kbws/ and GitHub repository http://github.com/cory-ko/KBWS. Users can utilize the SOAP services implemented in Perl directly via WSDL file at http://soap.g-language.org/kbws.wsdl (RPC Encoded) and http://soap.g-language.org/kbws_dl.wsdl (Document/literal).
LEF1 Identifies Androgen-Independent Epithelium in the Developing Prostate
Authors: Wu Xinyu , Daniels Garrett , Shapiro Ellen , Xu Kun , Huang Hongying , Li Yirong , Logan Susan , Greco M. Alba , Peng Yi , Monaco Marie E. , Melamed Jonathan , Lepor Herbert , Grishina Irina , Lee Peng
Published: April 2011

Lymphoid enhancer-binding factor (LEF)1 is a major mediator and a target in canonical Wnt/β-catenin pathway. Interactions between the androgen receptor (AR) and canonical Wnt pathways have been implicated in the development of the genitourinary organs. Here, we investigated the localization and role of LEF1-positive cells during development of the prostate gland in human and in the murine model. We show that during human prostate development, LEF1 is restricted to the basal epithelial layer of the urogenital sinus. During mouse development, Lef1 is also present in the urogenital mesenchyme in addition to the basal epithelial layer of the urogenital sinus. In the course of elongation and branching of the prostatic ducts, Lef1 is localized to the proliferating epithelium at the distal tips of the buds. Notably, during branching morphogenesis, domains of Lef1 and AR are mutually exclusive. We further employed the TOPGAL reporter strain to examine the dynamics of Wnt signaling in the context of prostate regression upon a 7-d treatment with a competitive AR inhibitor, bicalutamide. We found that Wnt/Lef1-positive basal cells are not dependent upon androgen for survival. Furthermore, upon bicalutamide treatment, Wnt/Lef1-positive basal progenitors repopulated the luminal compartment. We conclude that Wnt/Lef1 activity identifies an androgen-independent population of prostate progenitors, which is important for embryonic development and organ maintenance and regeneration in the adult.
Progesterone Receptor Directly Inhibits β-Casein Gene Transcription in Mammary Epithelial Cells Through Promoting Promoter and Enhancer Repressive Chromatin Modifications
Authors: Buser Adam C. , Obr Alison E. , Kabotyanski Elena B. , Grimm Sandra L. , Rosen Jeffrey M. , Edwards Dean P.
Published: April 2011

Differentiated HC-11 cells ectopically expressing progesterone receptor (PR) were used to explore the molecular mechanisms by which progesterone suppresses β-casein gene transcription induced by prolactin (PRL) and glucocorticoids in the mammary gland. As detected by chromatin immunoprecipitation assays, treatment of cells with the progestin agonist R5020 induced a rapid recruitment (5 min) of PR to the proximal promoter (−235 bp) and distal enhancer (−6 kb upstream of transcription start site) of β-casein. PR remained bound for 4 h and was dissociated by 24 h after treatment. Despite efficient binding, the hormone agonist-occupied PR did not stimulate transcription of the β-casein gene. Recruitment of signal transducer and activator of transcription 5a, glucocorticoid receptor, and the CCAAT enhancer binding protein β to the enhancer and proximal promoter of β-casein induced by PRL and glucocorticoids was blocked by progestin cotreatment, whereas PR binding was induced under these conditions. PRL/glucocorticoid-induced histone acetylation and the recruitment of the coactivator p300 and RNA polymerase II required for gene activation were also inhibited by progestin. In addition, progestin prevented dissociation of the corepressors Yin and Yang 1 and histone deacetylase 3 from the promoter, and demethylation of lysine 9 of histone 3 induced by PRL and glucocorticoids. These studies are consistent with the conclusion that progesterone interferes with PRL/glucocorticoid induction of β-casein transcription by a physical interaction of PR with the promoter and enhancer that blocks assembly of a transcriptional activation complex and dissociation of corepressors and promotes repressive chromatin modifications. These studies define a novel mechanism of steroid receptor-mediated transcriptional repression of a physiologically important gene in mammary gland development and differentiation.
Notes on Heinrich Isaac's Virgo prudentissima
Authors: Planchart Alejandro Enrique
Published: April 2011

Isaac's Virgo prudentissima, composed in 1507 for the Reichstag in Constance that confirmed Maximilian I as Holy Roman Emperor, is one of the composer's most complex and extended works. It is also a self-consciously constructivist piece that looks back to the repertoire of tenor motets pioneered by Guillaume Du Fay, Jehan de Ockeghem, and most prominently by Iohannes Regis. Yet its construction is markedly different from similar motets by his contemporary Josquin Des Prez, who used a nearly schematic construction in Miserere mei Deus, and ostinato techniques in Illibata Dei genitrix. This article takes a close look at Virgo prudentissima in order to show how Isaac achieves both a great deal of variety in textures and sonorities and a remarkable degree of motivic and thematic unity in the piece. The unity in Isaac's motet is largely due to an interplay of two basic textures and two kinds of motivic construction that are exposed in the first few sections of each pars and then fused in the concluding section, and to a judicious choice of which phrases of the cantus firmus—an antiphon for Vespers of the Assumption—he chooses to paraphrase in the free voices.

The motet's mensural structure—one section with all voices in ◯, and one with the tenor continuing in ◯ but the other five voices switching to ◯2, with semibreve-minim equivalence with the tenor—has been ignored entirely in all modern performances of the work that have been recorded in the last thirty years, usually with disastrous consequences for the performance of the secunda pars of the work. Isaac's notation is implausible until one realizes that he is using it for symbolic purposes and at the same time pointing to a correct tempo relationship between the partes by his organization of the phrase structure and the imitation at the beginning of the secunda pars. Isaac thus places this motet in what can be called a mensural tradition, which has its beginnings in the motets of Du Fay in the 1430s and in the wholesale adoption of the “English” relationship between triple and duple meters in the second half of the fifteenth century.
Writing the Disaster: Franklin and Frankenstein
Authors: Craciun Adriana
Published: April 2011

Adriana Craciun, “Writing the Disaster: Franklin and Frankenstein” (pp. 433–480)

The occasion for this essay is the surprise meeting of three texts from distinct traditions—Gothic romance, evangelical theology, and Enlightenment exploration—during the course of an Arctic disaster. The essay explores the relationship of the official disaster narrative (John Franklin's Narrative of a Journey to the Shores of the Polar Sea [1823]) to these heterogeneous textual companions, particularly Mary Shelley's Frankenstein (1818). Published by the Admiralty's official bookseller, John Murray, the official Franklin Narrative emerged from a highly centralized governmental and publishing network, one that attempted a virtual monopoly on prestigious Arctic publications from 1818 to 1848. The essay uncovers the complex institutional connections of this publishing nexus, and the strong centripetal pull exerted upon them by governmental authorities, while simultaneously considering a range of fugitive writings—chief among them Frankenstein—that escaped the pull of this formidable nexus. Frankenstein's proximity to the center of polar print culture and its highly regulated discursive practices reaffirms the widespread persistence not only of collaborative authorship into the nineteenth century, but also of more radically unindividualized authorship practices carried out across institutional lines. Thus, rather than asking how novels like Frankenstein were influenced by polar exploration, this essay broadens the field of inquiry to consider authorship and publishing practices across diverse domains, including corporate, governmental, and commercial.
John Clare and the Ghosts of Natures Past
Authors: Bewell Alan
Published: April 2011

Alan Bewell, “John Clare and the Ghosts of Natures Past” (pp. 548–578)

This essay seeks to read John Clare's poetry in terms of the poetry of exile. Clare directly confronted what it means to lose one's place in the world, to be exiled from a place not because you have left it, but because it has left you. No Romantic poet wrote more passionately than Clare about the joy of experiencing nature in all its immediacy, and no poet argued more strongly for its permanence and continuity across generations, and yet few poets have conveyed in more poignant terms what it means to lose one's nature for good. This paper considers Clare as a poet who writes about what it means to experience the end of nature and to live on long after the nature that one took to be basic to one's life was gone. Although for many people during the nineteenth century such an idea was unthinkable, for many others, especially in colonial contexts, it was a fact of life. Alongside the many new natures that were coming into being at this time, others were being destroyed or utterly changed. Clare's poetry gives us some insight into what it meant to at least one author to survive the death of one's nature.