bluuebunny/crossref_metadata_2025 huggingface dataset:
Mutations in the coding regions of the hepatocyte nuclear factor 4 alpha in Iranian families with maturity onset diabetes of the young
Authors: Taghavi Seyed Morteza , Fatemi Seyedeh Seddigheh , Rafatpanah Houshang , Ganjali Rashin , Tavakolafshari Jalil , Valizadeh Narges
Published: December 2009

Hepatocyte nuclear factor 4α (HNF4α) is a nuclear receptor involved in glucose homeostasis and is required for normal β cell function. Mutations in the HNF4α gene are associated with maturity onset diabetes of the young type 1 (MODY1). The aim of the present study was to determine the prevalence and nature of mutations in HNF4α gene in Iranian patients with a clinical diagnosis of MODY and their family members. Twelve families including 30 patients with clinically MODY diagnosis and 21 members of their family were examined using PCR-RFLP method and in case of mutation confirmed by sequencing techniques. Fifty age and sex matched subjects with normal fasting blood sugar (FBS) and Glucose tolerance test (GTT) were constituted the control group and investigated in the similar pattern. Single mutation of V255M in the HNF4α gene was detected. This known mutation was found in 8 of 30 patients and 3 of 21 individuals in relatives. Fifty healthy control subjects did not show any mutation. Here, it is indicated that the prevalence of HNF4α mutation among Iranian patients with clinical MODY is considerable. This mutation was present in 26.6% of our patients, but nothing was found in control group. In the family members, 3 subjects with the age of ≤25 years old carried this mutation. Therefore, holding this mutation in this range of age could be a predisposing factor for developing diabetes in future.
A comparative study of a flow-cytometry-based assessment of in vitro Plasmodium falciparum drug sensitivity
Authors: Karl Stephan , Wong Rina PM , St Pierre Tim G , Davis Timothy ME
Published: December 2009

Background

Recently developed Sybr Green-based in vitro Plasmodium falciparum drug sensitivity assays provide an attractive alternative to current manual and automated methods. The present study evaluated flow cytometry measurement of DNA staining with Sybr Green in comparison with the P. falciparum lactate dehydrogenase assay, the tritiated hypoxanthine incorporation assay, a previously described Sybr Green based plate reader assay and light microscopy.

Methods

All assays were set up in standardized format in 96-well plates. The 50% inhibitory concentrations (IC50) of chloroquine, mefloquine and dihydroartemisinin against the laboratory adapted P. falciparum strains 3D7, E8B, W2mef and Dd2 were determined using each method.

Results

The resolution achieved by flow cytometry allowed quantification of the increase in individual cell DNA content after an incubation period of only 24 h. Regression, and Bland and Altman analyses showed that the IC50 values determined using the flow cytometry assay after 24 h agreed well with those obtained using the hypoxanthine incorporation assay, the P. falciparum lactate dehydrogenase assay, the Sybr Green plate reader assay and light microscopy. However the values obtained with the flow cytometry assay after 48 h of incubation differed significantly from those obtained with the hypoxanthine incorporation assay, and the P. falciparum lactate dehydrogenase assay at low IC50 values, but agreed well with the Sybr Green plate reader assay and light microscopy.

Conclusions

Although flow cytometric equipment is expensive, the necessary reagents are inexpensive, the procedure is simple and rapid, and the cell volume required is minimal. This should allow field studies using fingerprick sample volumes.
Cultured skin microbiota attracts malaria mosquitoes
Authors: Verhulst Niels O , Beijleveld Hans , Knols Bart GJ , Takken Willem , Schraa Gosse , Bouwmeester Harro J , Smallegange Renate C
Published: December 2009

Background

Host-seeking of the African malaria mosquito, Anopheles gambiae sensu stricto, is guided by human odours. The precise nature of the odours, and the composition of attractive blends of volatiles, remains largely unknown. Skin microbiota plays an important role in the production of human body odours. It is hypothesized that host attractiveness and selection of An. gambiae is affected by the species composition, density, and metabolic activity of the skin microbiota. A study is presented in which the production and constituency of volatile organic compounds (VOCs) by human skin microbiota is examined and the behavioural responses of An. gambiae to VOCs from skin microbiota are investigated.

Methods

Blood agar plates incubated with skin microbiota from human feet or with a reference strain of Staphylococcus epidermidis were tested for their attractiveness to An. gambiae in olfactometer bioassays and indoor trapping experiments. Entrained air collected from blood agar plates incubated with natural skin microbiota or with S. epidermidis were analysed using GC-MS. A synthetic blend of the compounds identified was tested for its attractiveness to An. gambiae. Behavioural data were analysed by a χ2-test and GLM. GC-MS results were analysed by fitting an exponential regression line to test the effect of the concentration of bacteria.

Results

More An. gambiae were caught with blood agar plates incubated with skin bacteria than with sterile blood agar plates, with a significant effect of incubation time and dilution of the skin microbiota. When bacteria from the feet of four other volunteers were tested, similar effects were found. Fourteen putative attractants were found in the headspace of the skin bacteria. A synthetic blend of 10 of these was attractive to An. gambiae.

Conclusions

The discovery that volatiles produced by human skin microorganisms in vitro mediate An. gambiae host-seeking behaviour creates new opportunities for the development of odour-baited trapping systems. Additionally, identification of bacterial volatiles provides a new method to develop synthetic blends, attractive to An. gambiae and possibly other anthropophilic disease vectors.
Thermogenic effect of meltdown RTD™ energy drink in young healthy women: a double blind, cross-over design study
Authors: Rashti Stefanie L , Ratamess Nicholas A , Kang Jie , Faigenbaum Avery D , Chilakos Aristomen , Hoffman Jay R
Published: December 2009

Background

The purpose of this study was to examine the acute metabolic effects of a high-energy drink in healthy, physically-active women.

Methods

Ten women (20.4 ± 0.70 y; 166.9 ± 7.2 cm; 67.0 ± 7.0 kg; 29.6 ± 6.5% body fat) underwent two testing sessions administered in a randomized and double-blind fashion. Subjects reported to the laboratory in a 3-hr post-absorptive state and were provided either 140 ml of the high-energy drink (SUP; commercially marketed as Meltdown RTD™) or placebo (P). Subjects consumed two 70 ml doses of SUP or P, separated by 30 min and rested in a semi-recumbent position for 3 hours. Resting oxygen consumption (VO2) and heart rate (HR) were determined every 5 min during the first 30 min and every 10 min during the next 150 min. Blood pressure (BP) was determined every 15 min during the first 30 min and every 30 min thereafter. Area under the curve (AUC) analysis was computed for VO2, whereas a 3-hour average and hourly averages were calculated for respiratory quotient (RQ), total kcal, HR, BP, and profile of mood states (POMS).

Results

AUC analysis revealed a 10.8% difference (p = 0.03) in VO2 between SUP and P. No difference in VO2 was seen between the groups in the first hour, but VO2 in SUP was significantly greater than P in the second (13.9%, p = 0.01) and third hours (11.9%, p = 0.03). A difference (p = 0.03) in energy expenditure was seen between SUP (1.09 ± 0.10 kcal·min-1) and P (0.99 ± 0.09 kcal·min-1) for the 3-hour period. Although no difference in energy expenditure was seen in the first hour, significant differences between SUP and P were observed in the second (1.10 ± 0.11 kcal·min-1 and 0.99 ± 0.09 kcal·min-1, respectively; p = 0.02) and third hour (1.08 ± 0.11 kcal·min-1 and 0.99 ± 0.09 kcal·min-1, respectively; p = 0.05). Average systolic BP was significantly higher (p = 0.007) for SUP (110.0 ± 3.9 mmHg) compared to P (107.3 ± 4.4 mmHg). No differences were seen in HR, diastolic BP, or POMS at any time point.

Conclusions

Results showed a significant increase in energy expenditure in young, healthy women following an acute ingestion of a high-energy drink.
Copy number variation in the Framingham Heart Study
Authors: Shtir Corina , Pique-Regi Roger , Siegmund Kim , Morrison John , Schumacher Fredrick , Marjoram Paul
Published: December 2009

In this paper we test for association between copy number variation and diabetes in a subset of individuals from the Framingham Heart Study. We used the 500 k SNP data and called copy number variation using two algorithms: the genome alteration detection algorithm of Pique-Regi et al. and the software Golden Helix. We then tested for association between copy number and diabetes using a gene-based analysis. Our results show little evidence of association between copy number and diabetes status. Furthermore, our results indicate a relatively poor level of agreement between copy number calls resulting from the two programs. We then examined potential causes for this difference in results and the implications for future studies.
Application of imputation methods to the analysis of rheumatoid arthritis data in genome-wide association studies
Authors: Childers Douglas K , Kang Guolian , Liu Nianjun , Gao Guimin , Zhang Kui
Published: December 2009

Most genetic association studies only genotype a small proportion of cataloged single-nucleotide polymorphisms (SNPs) in regions of interest. With the catalogs of high-density SNP data available (e.g., HapMap) to researchers today, it has become possible to impute genotypes at untyped SNPs. This in turn allows us to test those untyped SNPs, the motivation being to increase power in association studies. Several imputation methods and corresponding software packages have been developed for this purpose. The objective of our study is to apply three widely used imputation methods and corresponding software packages to a data from a genome-wide association study of rheumatoid arthritis from the North American Rheumatoid Arthritis Consortium in Genetic Analysis Workshop 16, to compare the performances of the three methods, to evaluate their strengths and weaknesses, and to identify additional susceptibility loci underlying rheumatoid arthritis. The software packages used in this paper included a program for Bayesian imputation-based association mapping (BIMBAM), a program for imputing unobserved genotypes in case-control association studies (IMPUTE), and a program for testing untyped alleles (TUNA). We found some untyped SNP that showed significant association with rheumatoid arthritis. Among them, a few of these were not located near any typed SNP that was found to be significant and thus may be worth further investigation.
Genome-wide association studies of rheumatoid arthritis data via multiple hypothesis testing methods for correlated tests
Authors: Kang Guolian , Childers Douglas K , Liu Nianjun , Zhang Kui , Gao Guimin
Published: December 2009

Genome-wide association studies often involve testing hundreds of thousands of single-nucleotide polymorphisms (SNPs). These tests may be highly correlated because of linkage disequilibrium among SNPs. Multiple testing correction ignoring the correlation among markers, as is done in the Bonferroni procedure, can cause loss of power. Several multiple testing adjustment methods accounting for correlations among tests have been developed and have shown improved power compared to the Bonferroni procedure. These methods include a Monte Carlo (MC) method and a method of computing p-values adjusted for correlated tests. The objective of this study is to apply these two multiple testing methods to genome-wide association study of the Genetic Analysis Workshop 16 rheumatoid arthritis data from the North American Rheumatoid Arthritis Consortium, to compare the performance of these two methods to the Bonferroni procedure in identifying susceptibility loci underlying rheumatoid arthritis, and to discuss the strengths and weaknesses of these methods. The results show that both the MC method and p-values adjusted for correlated tests method identified more significant SNPs, thus potentially have higher power than the corresponding Bonferroni methods using the same test statistics as in the MC method and p-values adjusted for correlated tests, respectively. Simulation studies demonstrate that the MC method may have slightly higher power than the p-values adjusted for correlated tests method.
Detecting gene-by-smoking interactions in a genome-wide association study of early-onset coronary heart disease using random forests
Authors: Maenner Matthew J , Denlinger Loren C , Langton Asher , Meyers Kristin J , Engelman Corinne D , Skinner Halcyon G
Published: December 2009

Background

Genome-wide association studies are often limited in their ability to attain their full potential due to the sheer volume of information created. We sought to use the random forest algorithm to identify single-nucleotide polymorphisms (SNPs) that may be involved in gene-by-smoking interactions related to the early-onset of coronary heart disease.

Methods

Using data from the Framingham Heart Study, our analysis used a case-only design in which the outcome of interest was age of onset of early coronary heart disease.

Results

Smoking status was dichotomized as ever versus never. The single SNP with the highest importance score assigned by random forests was rs2011345. This SNP was not associated with age alone in the control subjects. Using generalized estimating equations to adjust for sex and account for familial correlation, there was evidence of an interaction between rs2011345 and smoking status.

Conclusion

The results of this analysis suggest that random forests may be a useful tool for identifying SNPs taking part in gene-by-environment interactions in genome-wide association studies.
Integration of a priori gene set information into genome-wide association studies
Authors: Sohns Melanie , Rosenberger Albert , Bickeböller Heike
Published: December 2009

In genome-wide association studies (GWAS) genetic markers are often ranked to select genes for further pursuit. Especially for moderately associated and interrelated genes, information on genes and pathways may improve the selection. We applied and combined two main approaches for data integration to a GWAS for rheumatoid arthritis, gene set enrichment analysis (GSEA) and hierarchical Bayes prioritization (HBP). Many associated genes are located in the HLA region on 6p21. However, the ranking lists of genes and gene sets differ considerably depending on the chosen approach: HBP changes the ranking only slightly and primarily contains HLA genes in the top 100 gene lists. GSEA includes also many non-HLA genes.
Bilateral choanal atresia in an adult - management with mitomycin C and without stents: a case report
Authors: Aksoy Fadlullah , Demirhan Hasan , Yildirim Yavuz Selim , Ozturan Orhan
Published: December 2009

Background

A 23-year-old female patient presented to the outpatient clinic with bilateral nasal obstruction and discharge since birth. Endoscopic examination and paranasal sinus tomography revealed bilateral choanal atresia. She did not have any other congenital abnormalities. Her parents reported cyanosis in childhood that worsened during feeding and improved during crying; however, they had not visited a physician. She did not have remarkable complaints during early childhood or adolescence.

Methods

The patient was operated under general anesthesia, using a 0° 4 mm rigid endoscope. The orifice was widened with a curette and, to prevent stenosis, mitomycin-C (1 mg/ml) was applied topically to the nasopharyngeal orifice for 5 minutes. No stents were placed.

Results

Follow-up evaluation at postoperative 12th month showed that her symptoms improved significantly and, on endoscopic examination, both choanae remained patent.
Separating therapeutic efficacy from glucocorticoid side-effects in rodent arthritis using novel, liposomal delivery of dexamethasone phosphate: long-term suppression of arthritis facilitates interval treatment
Authors: Rauchhaus Una , Schwaiger Franz Werner , Panzner Steffen
Published: December 2009

Introduction

Glucocorticoids have extensively been used in the treatment of rheumatoid arthritis and other inflammatory diseases. However, their side-effects remain the major limitation in clinical use and an improved therapeutic index is needed.

Methods

Therapeutic efficacy and persistence of free and liposomal dexamethasone phosphate (DXM-P) were determined in mouse collagen-induced arthritis. For regimens with equal therapeutic benefit, the side-effect profiles were analysed over time with respect to collagen breakdown, suppression of the hypothalamus-pituitary-adrenal (HPA) axis, changes in blood glucose levels and the haematological profile. In addition, the presence of drug was monitored in plasma.

Results

Liposomal DXM-P, but not free drug, resulted in a persistent anti-inflammatory effect. Comparable clinical benefit was achieved with a single administration of 4 mg/kg liposomal DXM-P or daily administrations of 1.6 mg/kg free drug for at least 7 days. For the liposomal form, but not for the free form, we observed a limitation of the suppression of the HPA axis in time and an absence of the drug-induced gluconeogenesis.

Conclusions

Liposomal DXM-P, but not free DXM-P, achieves therapeutic persistence in mouse collagen-induced arthritis, which results in drug-free periods of therapeutic benefit. The physical absence of drug after day 2 is associated with a reduction of the typical glucocorticoid side-effects profile. Liposomal DXM-P thereby has an improved therapeutic window.
Better assessment of physical function: item improvement is neglected but essential
Authors: Bruce Bonnie , Fries James F , Ambrosini Debbie , Lingala Bharathi , Gandek Barbara , Rose Matthias , Ware John E
Published: December 2009

Introduction

Physical function is a key component of patient-reported outcome (PRO) assessment in rheumatology. Modern psychometric methods, such as Item Response Theory (IRT) and Computerized Adaptive Testing, can materially improve measurement precision at the item level. We present the qualitative and quantitative item-evaluation process for developing the Patient Reported Outcomes Measurement Information System (PROMIS) Physical Function item bank.

Methods

The process was stepwise: we searched extensively to identify extant Physical Function items and then classified and selectively reduced the item pool. We evaluated retained items for content, clarity, relevance and comprehension, reading level, and translation ease by experts and patient surveys, focus groups, and cognitive interviews. We then assessed items by using classic test theory and IRT, used confirmatory factor analyses to estimate item parameters, and graded response modeling for parameter estimation. We retained the 20 Legacy (original) Health Assessment Questionnaire Disability Index (HAQ-DI) and the 10 SF-36's PF-10 items for comparison. Subjects were from rheumatoid arthritis, osteoarthritis, and healthy aging cohorts (n = 1,100) and a national Internet sample of 21,133 subjects.

Results

We identified 1,860 items. After qualitative and quantitative evaluation, 124 newly developed PROMIS items composed the PROMIS item bank, which included revised Legacy items with good fit that met IRT model assumptions. Results showed that the clearest and best-understood items were simple, in the present tense, and straightforward. Basic tasks (like dressing) were more relevant and important versus complex ones (like dancing). Revised HAQ-DI and PF-10 items with five response options had higher item-information content than did comparable original Legacy items with fewer response options. IRT analyses showed that the Physical Function domain satisfied general criteria for unidimensionality with one-, two-, three-, and four-factor models having comparable model fits. Correlations between factors in the test data sets were > 0.90.

Conclusions

Item improvement must underlie attempts to improve outcome assessment. The clear, personally important and relevant, ability-framed items in the PROMIS Physical Function item bank perform well in PRO assessment. They will benefit from further study and application in a wider variety of rheumatic diseases in diverse clinical groups, including those at the extremes of physical functioning, and in different administration modes.
The incidence of sub-optimal sedation in the ICU: a systematic review
Authors: Jackson Daniel L , Proudfoot Clare W , Cann Kimberley F , Walsh Tim S
Published: December 2009

Introduction

Patients in intensive care units (ICUs) are generally sedated for prolonged periods. Over-sedation and under-sedation both have negative effects on patient safety and resource use. We conducted a systematic review of the literature in order to establish the incidence of sub-optimal sedation (both over- and under-sedation) in ICUs.

Methods

We searched Medline, Embase and CINAHL (Cumulative Index to Nursing and Allied Health Literature) online literature databases from 1988 to 15 May 2008 and hand-searched conferences. English-language studies set in the ICU, in sedated adult humans on mechanical ventilation, which reported the incidence of sub-optimal sedation, were included. All abstracts were reviewed twice by two independent reviewers, with all conflicts resolved by a third reviewer, to check that they met the review inclusion criteria. Full papers of all included studies were retrieved and were again reviewed twice against inclusion criteria. Data were doubly extracted. Study aims, design, population, comparisons made, and data on the incidence of sub-optimal, optimal, over-sedation or under-sedation were extracted.

Results

There was considerable variation between included studies in the definition of optimal sedation and in the scale or method used to assess sedation. Across all included studies, a substantial incidence of sub-optimal sedation was reported, with a greater tendency toward over-sedation.

Conclusions

Our review suggests that improvements in the consistent definition and measurement of sedation may improve the quality of care of patients within the ICU.
A new miniaturized system for extracorporeal membrane oxygenation in adult respiratory failure
Authors: Müller Thomas , Philipp Alois , Luchner Andreas , Karagiannidis Christian , Bein Thomas , Hilker Michael , Rupprecht Leopold , Langgartner Julia , Zimmermann Markus , Arlt Matthias , Wenger Jan , Schmid Christof , Riegger Günter AJ , Pfeifer Michael , Lubnow Matthias
Published: December 2009

Introduction

Mortality of severe acute respiratory distress syndrome in adults is still unacceptably high. Extracorporeal membrane oxygenation (ECMO) could represent an important treatment option, if complications were reduced by new technical developments.

Methods

Efficiency, side effects and outcome of treatment with a new miniaturized device for veno-venous extracorporeal gas transfer were analysed in 60 consecutive patients with life-threatening respiratory failure.

Results

A rapid increase of partial pressure of arterial oxygen/fraction of inspired oxygen (PaO2/FiO2) from 64 (48 to 86) mmHg to 120 (84 to 171) mmHg and a decrease of PaCO2 from 63 (50 to 80) mmHg to 33 (29 to 39) mmHg were observed after start of the extracorporeal support (P < 0.001). Gas exchange capacity of the device averaged 155 (116 to 182) mL/min for oxygen and 210 (164 to 251) mL/min for carbon dioxide. Ventilatory parameters were reduced to a highly protective mode, allowing a fast reduction of tidal volume from 495 (401 to 570) mL to 336 (292 to 404) mL (P < 0.001) and of peak inspiratory pressure from 36 (32 to 40) cmH2O to 31 (28 to 35) cmH2O (P < 0.001). Transfusion requirements averaged 0.8 (0.4 to 1.8) units of red blood cells per day. Sixty-two percent of patients were weaned from the extracorporeal system, and 45% survived to discharge.

Conclusions

Veno-venous extracorporeal membrane oxygenation with a new miniaturized device supports gas transfer effectively, allows for highly protective ventilation and is very reliable. Modern ECMO technology extends treatment opportunities in severe lung failure.
Infections and autoimmunity: the multifaceted relationship
Authors: Sfriso Paolo , Ghirardello Anna , Botsios Costantino , Tonon Michele , Zen Margherita , Bassi Nicola , Bassetto Franco , Doria Andrea
Published: December 2009

The relationship between infections and autoimmunity as well as the risk of infections due to antirheumatic agents, including corticosteroids, immunosuppressants and biologics, are discussed.

Multiple factors are thought to contribute to the development of immune response to self, including differences in genotypes, hormonal milieu, and environmental factors. This review focuses on the pivotal role of infection in the induction of autoimmune disorders. Although the development of autoimmune phenomena linked to infections is a common finding, the onset of autoimmune diseases is a rare event, arising from a combination of genetic susceptibility and environmental factors. There are several mechanisms through which pathogens can initiate or perpetuate autoimmunity. Some of them are antigen-specific, including molecular mimicry, expression of modified, cryptic, or new antigenic determinants, and superantigens. Others are nonspecific and collectively known as “bystander activation.” They include enhanced processing and presentation of self-antigens, immune cell activation, cytokine release, and cell apoptosis/necrosis. Infections may also trigger organ-specific autoimmune diseases, but studies carried out until now have provided conflicting and inconclusive results regarding the role of viral and bacterial agents. Infections and autoimmune diseases have multifaceted and multidirectional relationships. It has been suggested recently that infections cannot only induce or precipitate autoimmune diseases, but they may also protect from autoimmunity or even abrogate an ongoing autoimmune process depending on the interaction between microorganisms and host. Therefore, we should look at microorganisms, not only as causes of infections but also as potential agents able to modulate the immune system. On the other hand, numerous evidences have emerged regarding the higher susceptibility of autoimmune patients to infections, possibly as a result of immunosuppressive therapy and treatment with biologic agents.
Up-Regulating the Heme Oxygenase System with Hemin Improves Insulin Sensitivity and Glucose Metabolism in Adult Spontaneously Hypertensive Rats
Authors: Ndisang Joseph Fomusi , Lane Nina , Syed Noor , Jadhav Ashok
Published: December 2009

Accumulating clinical evidence indicates that impaired glucose tolerance is a common phenomenon in essential hypertension. Although recent evidence underscores the role of heme-oxygenase (HO) in diabetes, its effects on insulin sensitivity and glucose metabolism in spontaneously hypertensive rat (SHR), a model of essential hypertension with characteristics of metabolic syndrome including insulin resistance/impaired glucose metabolism remains largely unclear. Here we report the effects of the HO inducer, hemin, and the HO blocker, chromium-mesoporphyrin on insulin sensitivity and glucose metabolism in SHRs. Adult SHRs were severely hypertensive but normoglycemic. Hemin therapy lowered blood pressure, increased plasma insulin, decreased glycemia, and enhanced insulin sensitivity by improving glucose tolerance (ip glucose tolerance test) and insulin tolerance (ip insulin tolerance test) but reduced insulin resistance (homeostasis model assessment index). These effects were accompanied by increased gastrocnemius muscle HO-1, HO activity, cGMP, cAMP alongside antioxidants including bilirubin, ferritin, superoxide dismutase, catalase, and the total antioxidant capacity, whereas oxidative/inflammatory mediators like 8-isoprostance, nuclear-factor-κB, activating-protein-1, activating-protein-2, c-Jun-NH2-terminal-kinase, and heme were abated. Furthermore, hemin reduced proteinuria/albuminuria and enhanced the depressed levels of adiponectin, AMP-activated protein-kinase, and glucose transporter-4 in SHRs, suggesting that although SHRs are normoglycemic, insulin signaling and renal function may be impaired. Contrarily, the HO inhibitor chromium-mesoporphyrin exacerbated oxidative stress, aggravated insulin resistance, glucose tolerance, insulin tolerance and nephropathy. Hemin also enhanced HO signaling in Wistar Kyoto and Sprague Dawley rats and increased insulin sensitivity albeit less intensely than in SHRs, suggesting greater selectivity of HO in SHRs with dysfunctional insulin signaling. These results suggest that perturbations of insulin signaling may be a forerunner to hyperglycemia in essential hypertension. By concomitantly potentiating insulin-sensitizing agents, suppressing insulin/glucose intolerance, and abating oxidative stress, HO inducers may prevent metabolic and cardiovascular complications in essential hypertension.
7α-Hydroxytestosterone Affects 11β-Hydroxysteroid Dehydrogenase 1 Direction in Rat Leydig Cells
Authors: Hu Guo-Xin , Lian Qing-Quan , Chen Bing-Bing , Prasad Pramod V. , Kumar Narender , Zheng Zhi-Qiang , Ge Ren-Shan
Published: December 2009

The cytochrome P450 2A1 (CYP2A1) is a P450 enzyme that catalyzes the metabolism of testosterone. CYP2A1 has been reported to be present in rat testis. However, its developmental changes and function have not been well characterized. The purpose of this study was to measure the abundance of CYP2A1 (Cyp2a1) mRNA in the developing rat testis and Leydig cells and examine the effects of its product, 7α-hydroxytestosterone (7HT), on an important enzyme, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) that interconverts active corticosterone and inactive 11-dehydrocorticosterone. As detected by real-time PCR, Cyp2a1 was found to be present exclusively in the Leydig cell. CYP2A1 activity in adult Leydig cells was 5-fold higher than those in progenitor or immature Leydig cells. 7HT competitively suppressed 11β-HSD1 oxidase and reductase activities in rat testis microsome with inhibitory constant of 1.2 and 2.9 μm, respectively. In intact Leydig cells, 7HT did not inhibit 11β-HSD1 reductase activity, but it stimulated its reductase activity. Thus, at 100 nm and higher concentrations, 7HT significantly switched 11β-HSD1 oxidoreductase activities toward reductase. The present data shows that 7HT, the product formed by CYP2A1 from testosterone, regulates the direction of 11β-HSD1 activity in rat Leydig cells.
Minireview: A Tiny Touch: Activation of Cell Signaling Pathways with Magnetic Nanoparticles
Authors: Sniadecki Nathan J.
Published: December 2009

Magnetic nanoparticles can be coated with specific ligands that enable them to bind to receptors on a cell’s surface. When a magnetic field is applied, it pulls on the particles so that they deliver nanoscale forces at the ligand-receptor bond. It has been observed that mechanical stimulation in this manner can activate cellular signaling pathways that are known as mechanotransduction pathways. Integrin receptors, stretch-activated ion channels, focal adhesions, and the cytoskeleton are key players in activating these pathways, but there is still much we do not know about how these mechanosensors work. Current evidence indicates that applied forces at these structures can activate Ca2+ signaling, Src family protein kinase, MAPK, and RhoGTPase pathways. The techniques of magnetic twisting and magnetic tweezers, which use magnetic particles to apply forces to cells, afford a fine degree of control over how cells are stimulated and hold much promise in elucidating the fundamentals of mechanotransduction. The particles are generally not harmful to cellular health, and their nanoscale dimensions make them advantageous for probing a cell’s molecular-scale sensory structures. This review highlights the basic aspects of magnetic nanoparticles, magnetic particle techniques and the structures and pathways that are involved in mechanotransduction.
Adipokine Profile and Urinary Albumin Excretion in Isolated Growth Hormone Deficiency
Authors: Oliveira Carla R. P. , Salvatori Roberto , Meneguz-Moreno Rafael A. , Aguiar-Oliveira Manuel H. , Pereira Rossana M. C. , Valença Eugênia H. A. , Araujo Vanessa P. , Farias Natália T. , Silveira Débora C. R. , Vieira Jose G. H. , Barreto-Filho Jose A. S.
Published: December 2009

Background: GH deficiency (GHD) is often associated with cardiovascular risk factors, including abdominal fat accumulation, hypercholesterolemia, and increased C-reactive protein. Despite the presence of these risk factors, adults with congenital lifetime isolated GHD (IGHD) due to an inactivating mutation in the GHRH receptor gene do not have premature atherosclerosis.

Objective: The aim was to study the serum levels of adiponectin and leptin (antiatherogenic and atherogenic adipokine, respectively), and the urinary albumin excretion (UAE) in these IGHD individuals.

Design and Patients: We conducted a cross-sectional study of 20 IGHD individuals (seven males; age, 50.8 ± 14.6 yr) and 22 control subjects (eight males; age, 49.9 ± 11.5 yr).

Main Outcome Measures: Anthropometric factors, body composition, blood pressure, serum adiponectin, leptin, and UAE were measured.

Results: Adiponectin was higher [12.8 (7.1) vs. 9.7 (5) ng/ml; P = 0.041] in IGHD subjects, whereas no difference was observed in leptin [7.3 (6.3) vs. 9.3 (18.7 ng/ml] and UAE [8.6 (13.8) vs. 8.5 (11.1) μg/min].

Conclusions: Subjects with lifetime untreated IGHD have an adipokine profile with high adiponectin and normal leptin levels that may delay vascular damage and lesions of the renal endothelium.
Federalism and Technological Change in Blood Products
Authors: Taylor Mark Zachary
Published: December 2009

Recent research has shown how federalism affects health care finance, health care reform, and health policy innovation. The purpose of this article is to extend this research program to study the linkages between federalism and technological change. It does so using comparative case studies spanning five countries to examine innovation and diffusion of two blood technologies—enzyme-linked immunosorbent assays (ELISA blood tests) and heat treatment—in response to the threat to the blood supply posed by HIV during the 1980s. Prior research has produced three contradictory models of the federalism-innovation relationship. This article attempts to resolve these contradictions, posits new hypotheses, and highlights sources of omitted variable bias that have important implications for understanding technological change. The case studies show that overall decentralization, rather than federalism alone, aids technological progress by allowing its supporters to “venue shop” around political resistance. Decentralization also makes the state less vulnerable to capture by status-quo interest groups. Moreover, political decentralization may have a positive effect on technological diffusion, but a far weaker effect on innovation. Thus, prior research that conflates these two effects should be revisited.
Maximizing Federal Medicaid Dollars: Nursing Home Provider Tax Adoption, 2000–2004
Authors: Miller Edward Alan , Wang Lili
Published: December 2009

Since Medicaid is jointly financed by the federal and state governments, state officials have sought to offset state expenditures by maximizing federal contributions. One such strategy is to adopt a provider tax, which enables states to collect revenues from providers; those revenues are then used to pay for services rendered to Medicaid recipients, thereby leveraging federal matching dollars without concomitant increases in state expenditures. The number of states adopting a nursing home tax increased from thirteen to thirty-one between 2000 and 2004. This study seeks to identify the factors that spurred the rapid increase in nursing home provider taxes following implementation of the Balanced Budget Act of 1997. Results indicate that states with more powerful nursing home lobbies, lower proportions of private pay nursing home residents, worse fiscal health, weaker fiscal capacity, broader Medicaid eligibility, and nursing home supply restrictions were more likely to adopt. This implies that state officials react rationally to prevailing fiscal and programmatic circumstances when formulating policy under Medicaid and that providers seek relief, in part, from the adverse fiscal consequences of federal policy changes by promoting policy change at the state level.
Performance-Based Regulation: Enterprise Responsibility for Reducing Death, Injury, and Disease Caused by Consumer Products
Authors: Sugarman Stephen D.
Published: December 2009

This article offers a bold new idea for confronting the staggering level of death, injury, and disease caused by five consumer products: cigarettes, alcohol, guns, junk food, and motor vehicles. Business leaders try to frame these negative outcomes as “collateral damage” that is someone else's problem. That framing not only is morally objectionable but also overlooks the possibility that, with proper prodding, industry could substantially lessen these public health disasters. I seek to reframe the public perception of who is responsible and propose to deploy a promising approach called “performance-based regulation” to combat the problem. Performance-based regulation would impose on manufacturers a legal obligation to reduce the negative social costs of their products. Rather than involving them in litigation or forcing them to operate differently (as “command-and-control” regimes do), performance-based regulation allows the firms to determine how best to decrease bad public health consequences. Like other public health strategies, performance-based regulation focuses on those who are far more likely than individual consumers to achieve real gains. Analogous to a tax on causing harm that exceeds a threshold level, performance-based regulation seeks to harness private initiative in pursuit of the public good.
Law and Finance “at the Origin”
Authors: Malmendier Ulrike
Published: December 2009

What are the key determinants of financial development and growth? A large literature debates the relative importance of countries' legal and political environment. In this paper, I present evidence from ancient Rome, where an early form of shareholder company, the societas publicanorum, developed. I show that the societas publicanorum flourished in a legally underdeveloped but politically supportive environment (Roman Republic) and disappeared when Roman law reached its height of legal sophistication but the political environment grew less supportive (Roman Empire). In the Roman case, legal development appears to have mattered little as long as the law as practiced was flexible and adapted to economic needs. The “law as practiced,” in turn, reflected prevalent political interests. After discussing parallels in more recent history, I provide a brief overview of the literature on law and finance and on politics and finance. The historical evidence suggests that legal systems may be less of a technological constraint for growth than previously thought—at least “at the origin.” (JEL D72, K10, N23, N43)
Laboratory reporting of hemostasis assays: the final post-analytical opportunity to reduce errors of clinical diagnosis in hemostasis?
Authors: Favaloro Emmanuel J. , Lippi Giuseppe
Published: December 2009

The advent of modern instrumentation, with associated improvements in test performance and reliability, together with appropriate internal quality control (IQC) and external quality assurance (EQA) measures, has led to substantial reductions in analytical errors within hemostasis laboratories. Unfortunately, the reporting of incorrect or inappropriate test results still occurs, perhaps even as frequently as in the past. Many of these cases arise due to a variety of events largely outside the control of the laboratories performing the tests. These events are primarily preanalytical, related to sample collection and processing, but can also include post-analytical events related to the reporting and interpretation of test results. The current report provides an overview of these events, as well as guidance for prevention or minimization. In particular, we propose several strategies for the post-analytical reporting of hemostasis assays, and how this may provide the final opportunity to prevent serious clinical errors in diagnosis. This report should be of interest to both the laboratory scientists working in hemostasis and clinicians that request and attempt to interpret the test results. Laboratory scientists are ultimately responsible for these test results, and there is a duty to provide both accurate and precise results to enable clinicians to manage patients appropriately and to avoid the need to recollect and retest. Also, clinicians will not be in a position to best diagnose and manage their patient unless they gain an appreciation of these issues.

Clin Chem Lab Med 2010;48:309–21.
Climate changes and technological advances: impacts on sugarcane productivity in tropical southern Brazil
Authors: Gouvêa Júlia Ribeiro Ferreira , Sentelhas Paulo Cesar , Gazzola Samuel Thomazella , Santos Marcelo Cabral
Published: December 2009

The climatic projections for this century indicate the possibility of severe consequences for human beings, especially for agriculture where adverse effects to productivity of crops and to agribusiness as a whole may occur. An agrometeorological model was used to estimate sugarcane yield in tropical southern Brazil, based on future A1B climatic scenarios presented in the fourth Intergovernmental Panel on Climate Change report, in 2007. Sugarcane yield was evaluated for 2020, 2050, and 2080 considering the possible impacts caused by changes in temperature, precipitation, sunshine hours and CO2 concentration in the atmosphere, as well as technological advances. Increasingly higher temperatures will cause an increase of the potential productivity (PP), since this variable positively affects the efficiency of the photosynthetic processes of C4 plants. Changes in solar radiation and rainfall, however, will have less impact. PP will increase by 15% in relation to the present condition in 2020, by 33% in 2050 and by 47% in 2080. Regarding the actual productivities (AP), the increase observed in PP will compensate for the negative effect of the projected increase in water deficit. AP will increase by 12% in relation to the present condition in 2020, by 32% in 2050 and by 47% in 2080. The increase in sugarcane productivity resulting from the projected scenarios will have important impacts on the sugarcane sector.
Restoration for Resistance to Invasion by Giant Reed (Arundo donax)
Authors: Quinn Lauren D. , Holt Jodie S.
Published: December 2009

The relationship between plant community composition and invasibility has been studied extensively but seldom in the context of ecosystem restoration. Experimental riparian restoration plots differing in species composition and density were established and evaluated for susceptibility to invasion by giant reed, a common riparian invader in California, and natural recruitment by riparian species over time. Plots were planted in 2002 with cuttings of common threesquare (a sedge), seepwillow (a shrub), and Goodding's willow (a tree) at two densities in monoculture and all possible mixture combinations. Giant reed rhizomes were introduced into half of the plots in the spring of 2003, while the remaining plots were allowed to undergo natural recruitment for an additional year. In late winter 2004, giant reed rhizomes were planted in the remaining plots. Both planting groups were followed for one growing season to evaluate giant reed establishment, survival, and growth. Community composition affected giant reed performance, particularly in 2003 before natural recruitment occurred. In that year, plots containing seepwillow + willow had the lowest giant reed shoot production, growth, and survival. All plots containing seepwillow were resistant to colonization by natural recruitment in 2004, but none of the planting treatments affected giant reed success in that year. Giant reed was more successful overall in 2004 despite deeper shade and drier soils. This pattern could be attributed to larger initial rhizome size in 2004, which allowed giant reed to overcome environmental stress during establishment. Planting density did not impact giant reed or natural recruitment independently, but may affect environmental parameters and warrants further study as a potential contributor to restoration success. Our results indicate that choice of species composition in restoration might impact giant reed invasion success initially, but community resistance might not be sustainable and maintenance-free over time.
Control of Seedling Sericea Lespedeza (Lespedeza cuneata) with Herbicides
Authors: Farris Rodney L. , Murray Don S.
Published: December 2009

Two field experiments were conducted at the Agronomy Research Station near Stillwater, OK in 2004 and 2005 to identify and evaluate herbicides applied preplant incorporated, preemergence, early postemergence, or late postemergence for the control of seedling sericea lespedeza. Trifluralin, applied preplant incorporated, controlled seedlings 77 (15 wk after emergence [WAE]) and 63% (16 WAE) in 2004 and 2005, respectively. Flumioxazin, imazapic, fluometuron, diuron, sulfentrazone, atrazine, metribuzin, and metolachlor applied preemergence all provided greater than 86% seedling control at 15 and 16 WAE in both years. Diclosulam, applied preemergent, controlled seedlings 47% at 15 WAE in 2004 and 91% control at 16 WAE in 2005. In 2004, triclopyr, metsulfuron-methyl, glyphosate, picloram, dicamba, and 2,4-D amine plus picloram (tank-mix) applied early postemergence controlled 90 to 100% of the sericea lespedeza seedlings at 15 WAE. However, in 2005, only triclopyr, metsulfuron-methyl, glyphosate, and 2,4-D amine plus picloram (tank-mix) showed greater than 80% control at 16 WAE. Triclopyr, applied late postemergence, controlled seedlings 100% at 15 and 16 WAE, in both years. In 2004, dicamba plus 2,4-D (premix) and glyphosate were the only other herbicides which provided greater than 75% control at 15 WAE. These data suggest that there were preemergence-applied herbicides that were effective for the control of seedling sericea lespedeza. These data also suggest that triclopyr was the most effective postemergence-applied herbicide for the control of seedling sericea lespedeza. The data also showed that the overall level of control of seedling sericea lespedeza decreased as the season progressed and the plant matured.