bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of thalidomide and lenalidomide as therapy for myelofibrosis
Authors: Jabbour Elias , Thomas Deborah , Kantarjian Hagop , Zhou Lingsha , Pierce Sherry , Cortes Jorge , Verstovsek Srdan
Published: May 2011

With the use of the International Working Group for Myelofibrosis Treatment and Research consensus criteria, we re-assessed the efficacy of thalidomide and lenalidomide in 125 patients with myelofibrosis treated in 3 consecutive phase 2 trials: 44 received single-agent thalidomide, 41 single-agent lenalidomide, and 40 a combination of lenalidomide plus prednisone. The thalidomide group included significantly more untreated patients and patients with performance status of 2. The Lenalidomide-based therapy produced higher efficacy (34%-38%) than thalidomide (16%; P = .06). Responses to thalidomide were seen within 3-15 weeks, whereas responses to the lenalidomide-based therapy were also seen after a prolonged course of therapy (range, 2-45 weeks). Lenalidomide plus prednisone therapy resulted in significantly longer response duration (median, 34 months) than single-agent lenalidomide or thalidomide (median, 7 and 13 months, respectively; P = .042). Fewer patients (P = .001) discontinued the lenalidomide plus prednisone therapy (13%) because of side effects then patients on single-agents therapy (32%-39%). In conclusion, the combination of lenalidomide plus prednisone appears to be more ef-fective and safer than single-agent thalidomide or lenalidomide.
Context-dependent codon partition models provide significant increases in model fit in atpB and rbcL protein-coding genes
Authors: Baele Guy , Van de Peer Yves , Vansteelandt Stijn
Published: May 2011

Background

Accurate modelling of substitution processes in protein-coding sequences is often hampered by the computational burdens associated with full codon models. Lately, codon partition models have been proposed as a viable alternative, mimicking the substitution behaviour of codon models at a low computational cost. Such codon partition models however impose independent evolution of the different codon positions, which is overly restrictive from a biological point of view. Given that empirical research has provided indications of context-dependent substitution patterns at four-fold degenerate sites, we take those indications into account in this paper.

Results

We present so-called context-dependent codon partition models to assess previous empirical claims that the evolution of four-fold degenerate sites is strongly dependent on the composition of its two flanking bases. To this end, we have estimated and compared various existing independent models, codon models, codon partition models and context-dependent codon partition models for the atpB and rbcL genes of the chloroplast genome, which are frequently used in plant systematics. Such context-dependent codon partition models employ a full dependency scheme for four-fold degenerate sites, whilst maintaining the independence assumption for the first and second codon positions.

Conclusions

We show that, both in the atpB and rbcL alignments of a collection of land plants, these context-dependent codon partition models significantly improve model fit over existing codon partition models. Using Bayes factors based on thermodynamic integration, we show that in both datasets the same context-dependent codon partition model yields the largest increase in model fit compared to an independent evolutionary model. Context-dependent codon partition models hence perform closer to codon models, which remain the best performing models at a drastically increased computational cost, compared to codon partition models, but remain computationally interesting alternatives to codon models. Finally, we observe that the substitution patterns in both datasets are drastically different, leading to the conclusion that combined analysis of these two genes using a single model may not be advisable from a context-dependent point of view.
Indole and 3-indolylacetonitrile inhibit spore maturation in Paenibacillus alvei
Authors: Kim Yong-Guy , Lee Jin-Hyung , Cho Moo Hwan , Lee Jintae
Published: May 2011

Background

Bacteria use diverse signaling molecules to ensure the survival of the species in environmental niches. A variety of both Gram-positive and Gram-negative bacteria produce large quantities of indole that functions as an intercellular signal controlling diverse aspects of bacterial physiology.

Results

In this study, we sought a novel role of indole in a Gram-positive bacteria Paenibacillus alvei that can produce extracellular indole at a concentration of up to 300 μM in the stationary phase in Luria-Bertani medium. Unlike previous studies, our data show that the production of indole in P. alvei is strictly controlled by catabolite repression since the addition of glucose and glycerol completely turns off the indole production. The addition of exogenous indole markedly inhibits the heat resistance of P. alvei without affecting cell growth. Observation of cell morphology with electron microscopy shows that indole inhibits the development of spore coats and cortex in P. alvei. As a result of the immature spore formation of P. alvei, indole also decreases P. alvei survival when exposed to antibiotics, low pH, and ethanol. Additionally, indole derivatives also influence the heat resistance; for example, a plant auxin, 3-indolylacetonitrile dramatically (2900-fold) decreased the heat resistance of P. alvei, while another auxin 3-indoleacetic acid had a less significant influence on the heat resistance of P. alvei.

Conclusions

Together, our results demonstrate that indole and plant auxin 3-indolylacetonitrile inhibit spore maturation of P. alvei and that 3-indolylacetonitrile presents an opportunity for the control of heat and antimicrobial resistant spores of Gram-positive bacteria.
Histone deacetylase inhibitors SAHA and sodium butyrate block G1-to-S cell cycle progression in neurosphere formation by adult subventricular cells
Authors: Zhou Qiong , Dalgard Clifton L , Wynder Christopher , Doughty Martin L
Published: May 2011

Background

Histone deacetylases (HDACs) are enzymes that modulate gene expression and cellular processes by deacetylating histones and non-histone proteins. While small molecule inhibitors of HDAC activity (HDACi) are used clinically in the treatment of cancer, pre-clinical treatment models suggest they also exert neuroprotective effects and stimulate neurogenesis in neuropathological conditions. However, the direct effects of HDACi on cell cycle progression and proliferation, two properties required for continued neurogenesis, have not been fully characterized in adult neural stem cells (NSCs). In this study, we examined the effects of two broad class I and class II HDACi on adult mouse NSCs, the hydroxamate-based HDACi suberoylanilide hydroxamic acid (vorinostat, SAHA) and the short chain fatty acid HDACi sodium butyrate.

Results

We show that both HDACi suppress the formation of neurospheres by adult mouse NSCs grown in proliferation culture conditions in vitro. DNA synthesis is significantly inhibited in adult mouse NSCs exposed to either SAHA or sodium butyrate and inhibition is associated with an arrest in the G1 phase of the cell cycle. HDACi exposure also resulted in transcriptional changes in adult mouse NSCs. Cdk inhibitor genes p21 and p27 transcript levels are increased and associated with elevated H3K9 acetylation levels at proximal promoter regions of p21 and p27. mRNA levels for notch effector Hes genes and Spry-box stem cell transcription factors are downregulated, whereas pro-neural transcription factors Neurog1 and Neurod1 are upregulated. Lastly, we show HDAC inhibition under proliferation culture conditions leads to long-term changes in cell fate in adult mouse NSCs induced to differentiate in vitro.

Conclusion

SAHA and sodium butyrate directly regulate cdk inhibitor transcription to control cell cycle progression in adult mouse NSCs. HDAC inhibition results in G1 arrest in adult mouse NSCs and transcriptional changes associated with activation of neuronal lineage commitment programs and a reduction of stem/progenitor state. Changes in differentiated cell state in adult mouse NSCs treated with HDACi under proliferation culture conditions suggests an intrinsic relationship between multipotency, cell cycle progression and HDAC activity in these cells.
P53 in human melanoma fails to regulate target genes associated with apoptosis and the cell cycle and may contribute to proliferation
Authors: Avery-Kiejda Kelly A , Bowden Nikola A , Croft Amanda J , Scurr Lyndee L , Kairupan Carla F , Ashton Katie A , Talseth-Palmer Bente A , Rizos Helen , Zhang Xu D , Scott Rodney J , Hersey Peter
Published: May 2011

Background

Metastatic melanoma represents a major clinical problem. Its incidence continues to rise in western countries and there are currently no curative treatments. While mutation of the P53 tumour suppressor gene is a common feature of many types of cancer, mutational inactivation of P53 in melanoma is uncommon; however, its function often appears abnormal.

Methods

In this study whole genome bead arrays were used to examine the transcript expression of P53 target genes in extracts from 82 melanoma metastases and 6 melanoma cell lines, to provide a global assessment of aberrant P53 function. The expression of these genes was also examined in extracts derived from diploid human melanocytes and fibroblasts.

Results

The results indicated that P53 target transcripts involved in apoptosis were under-expressed in melanoma metastases and melanoma cell lines, while those involved in the cell cycle were over-expressed in melanoma cell lines. There was little difference in the transcript expression of P53 target genes between cell lines with null/mutant P53 compared to those with wild-type P53, suggesting that altered expression in melanoma was not related to P53 status. Similarly, down-regulation of P53 by short-hairpin RNA (shRNA) had limited effect on P53 target gene expression in melanoma cells, whereas there were a large number of P53 target genes whose mRNA expression was significantly altered by P53 inhibition in melanocytes. Analysis of whole genome gene expression profiles indicated that the ability of P53 to regulate genes involved in the cell cycle was significantly reduced in melanoma cells. Moreover, inhibition of P53 in melanocytes induced changes in gene expression profiles that were characteristic of melanoma cells and resulted in increased proliferation. Conversely, knockdown of P53 in melanoma cells resulted in decreased proliferation.

Conclusions

These results indicate that P53 target genes involved in apoptosis and cell cycle regulation are aberrantly expressed in melanoma and that this aberrant functional activity of P53 may contribute to the proliferation of melanoma.
Real-time visualization of heterotrimeric G protein Gq activation in living cells
Authors: Adjobo-Hermans Merel JW , Goedhart Joachim , van Weeren Laura , Nijmeijer Saskia , Manders Erik MM , Offermanns Stefan , Gadella Theodorus WJ
Published: May 2011

Background

Gq is a heterotrimeric G protein that plays an important role in numerous physiological processes. To delineate the molecular mechanisms and kinetics of signalling through this protein, its activation should be measurable in single living cells. Recently, fluorescence resonance energy transfer (FRET) sensors have been developed for this purpose.

Results

In this paper, we describe the development of an improved FRET-based Gq activity sensor that consists of a yellow fluorescent protein (YFP)-tagged Gγ2 subunit and a Gαq subunit with an inserted monomeric Turquoise (mTurquoise), the best cyan fluorescent protein variant currently available. This sensor enabled us to determine, for the first time, the kon (2/s) of Gq activation. In addition, we found that the guanine nucleotide exchange factor p63RhoGEF has a profound effect on the number of Gq proteins that become active upon stimulation of endogenous histamine H1 receptors. The sensor was also used to measure ligand-independent activation of the histamine H1 receptor (H1R) upon addition of a hypotonic stimulus.

Conclusions

Our observations reveal that the application of a truncated mTurquoise as donor and a YFP-tagged Gγ2 as acceptor in FRET-based Gq activity sensors substantially improves their dynamic range. This optimization enables the real-time single cell quantification of Gq signalling dynamics, the influence of accessory proteins and allows future drug screening applications by virtue of its sensitivity.
Yellow fever virus envelope protein expressed in insect cells is capable of syncytium formation in lepidopteran cells and could be used for immunodetection of YFV in human sera
Authors: Barros Maria CES , Galasso Tatiane GCM , Chaib Antônio JM , Degallier Nicolas , Nagata Tatsuya , Ribeiro Bergmann M
Published: May 2011

Background

Yellow fever is an haemorrhagic disease caused by a virus that belongs to the genus Flavivirus (Flaviviridae family) and is transmitted by mosquitoes. Among the viral proteins, the envelope protein (E) is the most studied one, due to its high antigenic potencial. Baculovirus are one of the most popular and efficient eukaryotic expression system. In this study a recombinant baculovirus (vSynYFE) containing the envelope gene (env) of the 17D vaccine strain of yellow fever virus was constructed and the recombinant protein antigenicity was tested.

Results

Insect cells infected with vSynYFE showed syncytium formation, which is a cytopathic effect characteristic of flavivirus infection and expressed a polypeptide of around 54 kDa, which corresponds to the expected size of the recombinant E protein. Furthermore, the recombinant E protein expression was also confirmed by fluorescence microscopy of vSynYFE-infected insect cells. Total vSynYFE-infected insect extracts used as antigens detected the presence of antibodies for yellow fever virus in human sera derived from yellow fever-infected patients in an immunoassay and did not cross react with sera from dengue virus-infected patients.

Conclusions

The E protein expressed by the recombinant baculovirus in insect cells is antigenically similar to the wild protein and it may be useful for different medical applications, from improved diagnosis of the disease to source of antigens for the development of a subunit vaccine.
Growth and development of Gnathostoma spinigerum (Nematoda: Gnathostomatidae) larvae in Mesocyclops aspericornis (Cyclopoida: Cyclopidae)
Authors: Janwan Penchom , Intapan Pewpan M , Sanpool Oranuch , Sadaow Luxkhana , Thanchomnang Tongjit , Maleewong Wanchai
Published: May 2011

Background

Gnathostoma spinigerum larva is pathogenic, causing gnathostomiasis in humans and certain animals, and is prevalent mainly in Asia. Growth and development of Gnathostoma spinigerum larvae in the cyclopoid copepod Mesocyclops aspericornis, the first intermediate host, were examined.

Results

When newly hatched, ensheathed second-stage larvae (L2) were ingested by M. aspericornis, they immediately appeared exsheathed in the stomach of M. aspericornis. They then penetrated the stomach wall and entered the body cavity, where they immediately metamorphosed to a stunted form with the body length/width ratio equal to the early third-stage larvae (EL3) up to 2 h after being ingested. During metamorphosis, the anterior spine-like structure of L2 transformed into unequal transparent lips. The larvae moulted into EL3 in the body cavity of the copepod at around day 5-7 post-infection. Minute cuticular striations were seen on the whole body, with prominent single-pointed spines on the anterior part of the body. The head bulb had four rows of hooklets and two lateral trilobed lips. The size of EL3 in copepods continuously increased towards day 12 and showed a negative correlation to their density per copepod (R = -0.881, P < 0.05 for body length, and R = -0.906, P < 0.05 for body width).

Conclusions

The results revealed for the first time that M. aspericornis, one of the most abundant freshwater copepods in Thailand, is a suitable first intermediate host for G. spinigerum. High susceptibility of M. aspericornis suggests its importance for the maintenance of the life cycle of G. spinigerum in Thailand.
The ShakeOut Earthquake Source and Ground Motion Simulations
Authors: Graves Robert W. , Aagaard Brad T. , Hudnut Kenneth W.
Published: May 2011

The ShakeOut Scenario is premised upon the detailed description of a hypothetical Mw 7.8 earthquake on the southern San Andreas Fault and the associated simulated ground motions. The main features of the scenario, such as its endpoints, magnitude, and gross slip distribution, were defined through expert opinion and incorporated information from many previous studies. Slip at smaller length scales, rupture speed, and rise time were constrained using empirical relationships and experience gained from previous strong-motion modeling. Using this rupture description and a 3-D model of the crust, broadband ground motions were computed over a large region of Southern California. The largest simulated peak ground acceleration (PGA) and peak ground velocity (PGV) generally range from 0.5 to 1.0 g and 100 to 250 cm/s, respectively, with the waveforms exhibiting strong directivity and basin effects. Use of a slip-predictable model results in a high static stress drop event and produces ground motions somewhat higher than median level predictions from NGA ground motion prediction equations (GMPEs).
Lines and Crimes of Demarcation: Mathematizing Nature in Heidegger, Pynchon, and Kehlmann
Authors: Ireton Sean
Published: May 2011

In his bestselling novel from 2005, Die Vermessung der Welt (Measuring the World), Daniel Kehlmann brings together the explorer Alexander von Humboldt and the mathematician Carl Friedrich Gauss in an effort to show that the scientific progress preached by the Enlightenment is a double-edged sword. Hence the double entendre of the title: Humboldt's and Gauss's “surveying” (Vermessung) enterprises typify human “arrogance” (Vermessenheit) toward nature. The ideas presented in Kehlmann's book were no doubt influenced by Thomas Pynchon's Mason & Dixon (1997), a metafictional history in which the Mason and Dixon survey is represented as a rationalist endeavor that transforms the primitive American landscape into an organized grid of human control. Both authors are critiquing, from a postmodern vantage, eighteenth-century instrumental reason, which manifests itself in the urge to measure, chart, and demarcate the world. At various points in his narrative, Pynchon sums up this basic anthropocentric view as mathesis, a term that recalls the early modern scientific project of mathesis universalis or the attempt to “mathematize” nature. According to Heidegger, mathesis, which sums up our modern technological attitude toward the world, developed as a result of Galilean geometry, Newtonian science, and Cartesian philosophy, all of which conceptualize reality according to purely speculative mathematical laws. This article brings Heidegger, Pynchon, and Kehlmann into dialogue with one another in an effort to show how they each critique, in remarkably similar fashion, the conceptual as well as physical lines of demarcation that mathesis inflicts upon the world.
Race–ethnicity as an effect modifier of the association between HbAlc and mortality in U.S. adults without diagnosed diabetes
Authors: Kehl Katharina G , Findeisen Hannes M , Fardo David W , Bruemmer Dennis , Mannino David M , Sanderson Wayne T
Published: May 2011

Objective

HbAlc is increasingly appreciated as a risk factor for all-cause and cardiovascular disease (CVD) mortality in the non-diabetic population. In this study, we investigated the association between HbAlc and mortality with a particular focus on the impact of race–ethnicity.

Design

Cohort study.

Methods

We analyzed the association between HbAlc and all-cause and CVD mortality in 12 698 non-diabetic adults 20 years or older from the Third National Health and Nutrition Examination Survey using separate models for people of different race–ethnicity.

Results

In our stratified analyses, higher non-diabetic HbAlc levels were associated with all-cause and CVD mortality in non-Hispanic whites only. In this group, compared with HbAlc values of 5.0–<5.35%, the multivariable-adjusted estimated hazard ratios (est. HR) with 95% confidence interval (CI) for all-cause mortality were 1.21 (0.92, 1.58), 1.22 (1.03, 1.45), 1.29 (1.14, 1.47), and 1.4 (1.02, 1.87) for HbAlc levels of <5.0, 5.35–<5.7, 5.7–<6.5, and 6.5% or greater respectively. The association did not reach significance in Mexican–Americans (est. HR (95% CI): 1.77 (1.08, 2.91), 0.81 (0.56, 1.19), 1.16 (0.86, 1.57), and 1.4 (0.83, 2.36)). No association was observed in non-Hispanic blacks: 1.13 (0.91, 1.39), 0.81 (0.61, 1.08), 0.84 (0.69, 1.03), and 0.94 (0.67, 1.33). Results were similar for CVD mortality.

Conclusions

Our data suggest limitations of HbAlc as a risk factor for all-cause and cardiovascular mortality across race–ethnic populations.
Bupropion‐Induced Acute Generalized Exanthematous Pustulosis
Authors: Ray Abbie K. , Wall Geoffrey C.
Published: May 2011

Acute generalized exanthematous pustulosis (AGEP) is a severe cutaneous reaction almost always associated with drug therapy. Antimicrobials, anticonvulsants, and nonsteroidal antiinflammatory drugs have the highest association with this adverse reaction, but numerous drugs have been implicated. We describe a 43‐year‐old woman with a history of major depressive disorder who was prescribed bupropion. Approximately 10 days after starting therapy, the patient noticed a rash with small, pustular, erythematous lesions on her arms and thighs. The lesions subsequently coalesced and spread further up her arms and onto her buttocks. Five days after onset of the rash, she came to the emergency department. The patient's symptoms included malaise and fever. She had no mucosal involvement, and laboratory analysis was largely normal except for neutrophilia. Biopsy of the pustules revealed focal, mild hyper‐ and parakeratosis, acanthosis, spongiosis with papillary edema, and exocytosis of neutrophils consistent with AGEP. Discontinuation of bupropion and supportive care resulted in significant improvement in all symptoms during the next 4 days, and the patient was discharged in good condition. This patient had both clinical and histologic findings consistent with AGEP. The European Severe Cutaneous Adverse Reactions (EuroSCAR) study scale suggested that this case was definitely caused by bupropion (score of 11), whereas the Naranjo adverse drug reaction probability scale suggested that this case was probably caused by the drug (score of 6). Treatment for AGEP is largely supportive, and most patients completely recover within 15 days of discontinuing the implicated drug. To our knowledge, this is the first reported case of bupropion‐induced AGEP Clinicians caring for patients taking bupropion should be aware of this rare but serious cutaneous adverse effect.
Focal Segmental Glomerulosclerosis with Acute Renal Failure Associated with Eltrombopag Therapy
Authors: Teng Chung‐Jen , Hong Ying‐Chung , Chiang Huey‐Ling , Liu Han‐Tsun , Liu Chia‐Jen , Yang An‐Hang , Liu Jin‐Hwang , Wang Wei‐Shu , Tzeng Cheng‐Hwai
Published: May 2011

Eltrombopag, a small‐molecule nonpeptide agonist of the thrombopoietin receptor, is used for treatment of thrombocytopenia of various causes, including chronic idiopathic thrombocytopenic purpura (ITP) and hepatitis C‐related liver cirrhosis. During clinical trials, eltrombopag was discontinued in three patients due to ascites, neutropenia, and retinal exudates. Another recently reported major adverse event was reversible acute renal failure in a patient with antiphospholipid syndrome; nephrotoxicity caused by eltrombopag was highly suspected, but a kidney biopsy was not performed. We describe a 46‐year‐old woman with a history of mitral valve prolapse who had an incidental finding of an isolated low platelet count of 22 × 103/mm3. A tentative diagnosis of ITP was made, and oral prednisolone 25 mg twice/day was started. Despite prednisolone dosage adjustments over the next several weeks, her platelet count remained at 15–40 × 103/mm3, and oral eltrombopag 75 mg/day was begun. After seven doses, the patient came to the emergency department with persistent nausea and vomiting. Laboratory work‐up revealed renal failure, and eltrombopag was discontinued. The patient was hospitalized, and on day 2, her renal failure had progressed, and proteinuria was detected. On day 6, emergency hemodialysis was begun. A complete blood count on day 21 revealed progression of anemia and thrombocytopenia. Splenectomy was performed on day 35, which successfully reversed her thrombocytopenia. She was discharged on day 39, and hemodialysis was discontinued on day 44. At follow‐up on day 56, the patient's platelet count was within normal limits. On day 70, kidney biopsy results revealed a typical pattern of focal segmental and diffuse global glomerulosclerosis. By day 210, her ITP had resolved, and her renal function was stable. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 7) between the patient's development of acute renal failure and eltrombopag therapy. To our knowledge, this is the first case report of a patient who experienced acute renal failure and proteinuria concomitant with a pathology of focal segmental glomerulosclerosis after treatment with eltrombopag. This report of a serious case of reversible renal failure after treatment with eltrombopag may serve to inform clinicians about the possible severe renal adverse effects of eltrombopag before commencing with more extensive clinical use in the future.
Estimated Glomerular Filtration Rate Is a Poor Predictor of Concentration for a Broad Range of Uremic Toxins
Authors: Eloot Sunny , Schepers Eva , Barreto Daniela V. , Barreto Fellype C. , Liabeuf Sophie , Van Biesen Wim , Verbeke Francis , Glorieux Griet , Choukroun Gabriel , Massy Ziad , Vanholder Raymond
Published: May 2011

Background and objectives

The degree of chronic kidney disease (CKD) is currently expressed in terms of GFR, which can be determined directly or estimated according to different formulas on the basis of serum creatinine and/or cystatin C measurements (estimated GFR [eGFR]). The purpose of this study was to investigate whether eGFR values are representative for uremic toxin concentrations in patients with different degrees of CKD.

Design, setting, participants, & measurements

Associations between eGFR based on serum cystatin C and different uremic solutes (mol wt range 113 to 240 D; determined by colorimetry, HPLC, or ELISA) were evaluated in 95 CKD patients not on dialysis (CKD stage 2 to 5). The same analysis was also applied for six other eGFR formulas.

Results

There was a substantial disparity in fits among solutes. In linear regression, explained variance of eGFR was extremely low for most solutes, with eGFR > 0.4 only for creatinine. The other eGFR formulations gave comparably disappointing results with regard to their association to uremic solutes. Relative similarity in R
2 values per solute for the different eGFR values and the strong disparity in values between solutes suggest that the differences in R
2 are mainly due to discrepancies in solute handling apart from GFR.

Conclusions

eGFR is poorly associated with concentrations of all studied uremic toxins in patients with different degrees of CKD, correlates differently with each individual solute, and can thus not be considered representative for evaluating the accumulation of solutes in the course of CKD.
Is Coronary Artery Calcification Associated with Vertebral Bone Density in Nondialyzed Chronic Kidney Disease Patients?
Authors: Filgueira Agostinho , Carvalho Aluizio Barbosa , Tomiyama Cristiane , Higa Andrea , Rochitte Carlos E. , Santos Raul D. , Canziani Maria Eugênia F.
Published: May 2011

Background and objectives

Low bone mineral density and coronary artery calcification (CAC) are highly prevalent among chronic kidney disease (CKD) patients, and both conditions are strongly associated with higher mortality. The study presented here aimed to investigate whether reduced vertebral bone density (VBD) was associated with the presence of CAC in the earlier stages of CKD.

Design, setting, participants, & measurements

Seventy-two nondialyzed CKD patients (age 52 ± 11.7 years, 70% male, 42% diabetics, creatinine clearance 40.4 ± 18.2 ml/min per 1.73 m2) were studied. VBD and CAC were quantified by computed tomography.

Results

CAC > 10 Agatston units (AU) was observed in 50% of the patients (median 120 AU [interquartile range 32 to 584 AU]), and a calcification score ≥ 400 AU was found in 19% (736 [527 to 1012] AU). VBD (190 ± 52 Hounsfield units) correlated inversely with age (r = −0.41, P < 0.001) and calcium score (r = −0.31, P = 0.01), and no correlation was found with gender, creatinine clearance, proteinuria, lipid profile, mineral parameters, body mass index, and diabetes. Patients in the lowest tertile of VBD had expressively increased calcium score in comparison to the middle and highest tertile groups. In the multiple logistic regression analysis adjusting for confounding variables, low VBD was independently associated with the presence of CAC.

Conclusions

Low VBD was associated with CAC in nondialyzed CKD patients. The authors suggest that low VBD might constitute another nontraditional risk factor for cardiovascular disease in CKD.
Activation of Peroxisome Proliferator–Activated Receptor-β/-δ (PPAR-β/-δ) Ameliorates Insulin Signaling and Reduces SOCS3 Levels by Inhibiting STAT3 in Interleukin-6–Stimulated Adipocytes
Authors: Serrano-Marco Lucía , Rodríguez-Calvo Ricardo , El Kochairi Ilhem , Palomer Xavier , Michalik Liliane , Wahli Walter , Vázquez-Carrera Manuel
Published: May 2011

OBJECTIVE

It has been suggested that interleukin (IL)-6 is one of the mediators linking obesity-derived chronic inflammation with insulin resistance through activation of STAT3, with subsequent upregulation of suppressor of cytokine signaling 3 (SOCS3). We evaluated whether peroxisome proliferator–activated receptor (PPAR)-β/-δ prevented activation of the IL-6-STAT3-SOCS3 pathway and insulin resistance in adipocytes.

RESEARCH DESIGN AND METHODS

Adipocytes and white adipose tissue from wild-type and PPAR-β/-δ-null mice were used to evaluate the effect of PPAR-β/-δ on the IL-6-STAT3-SOCS3 pathway.

RESULTS

First, we observed that the PPAR-β/-δ agonist GW501516 prevented both IL-6–dependent reduction in insulin-stimulated Akt phosphorylation and glucose uptake in adipocytes. In addition, this drug treatment abolished IL-6–induced SOCS3 expression in differentiated 3T3-L1 adipocytes. This effect was associated with the capacity of the drug to prevent IL-6–induced STAT3 phosphorylation on Tyr705 and Ser727 residues in vitro and in vivo. Moreover, GW501516 prevented IL-6–dependent induction of extracellular signal–related kinase (ERK)1/2, a serine-threonine-protein kinase involved in serine STAT3 phosphorylation. Furthermore, in white adipose tissue from PPAR-β/-δ–null mice, STAT3 phosphorylation (Tyr705 and Ser727), STAT3 DNA-binding activity, and SOCS3 protein levels were higher than in wild-type mice. Several steps in STAT3 activation require its association with heat shock protein 90 (Hsp90), which was prevented by GW501516 as revealed in immunoprecipitation studies. Consistent with this finding, the STAT3-Hsp90 association was enhanced in white adipose tissue from PPAR-β/-δ–null mice compared with wild-type mice.

CONCLUSIONS

Collectively, our findings indicate that PPAR-β/-δ activation prevents IL-6–induced STAT3 activation by inhibiting ERK1/2 and preventing the STAT3-Hsp90 association, an effect that may contribute to the prevention of cytokine-induced insulin resistance in adipocytes.
Retinol-Binding Protein 4 Is Associated With Prediabetes in Adults From the General Population
Authors: Meisinger Christa , Rückert Ina M. , Rathmann Wolfgang , Döring Angela , Thorand Barbara , Huth Cornelia , Kowall Bernd , Koenig Wolfgang
Published: May 2011

OBJECTIVE

We examined the association between retinol-binding protein 4 (RBP4), a novel adipokine, and prediabetes (isolated impaired fasting glucose [i-IFG], isolated impaired glucose tolerance [i-IGT], and combined IFG and IGT) in men and women aged 32–81 years.

RESEARCH DESIGN AND METHODS

The analysis was based on 2,614 participants without previously diagnosed diabetes and those with newly diagnosed diabetes of the Cooperative Health Research in the Region of Augsburg (KORA) F4 Study, conducted from 2006 to 2008 in southern Germany. Plasma RBP4 was analyzed by immunonephelometry.

RESULTS

In logistic regression analysis, RBP4 levels in the fourth quartile versus the first quartile were significantly associated with prediabetes (i-IGT, i-IFG, and IFG/IGT; reference normal glucose tolerance) independent of known metabolic risk factors and lifestyle variables (odds ratio 1.63 [95% CI 1.17–2.27] after multivariable adjustment). Stratification by sex showed generally similar results.

CONCLUSIONS

RBP4 levels were associated with prediabetes in individuals from the general population. Prospective studies investigating the impact of RBP4 on the development of glucose intolerance are needed.
Indirect Evidences of Wildlife Activities in Shoals of Western Ghats, a Biodiversity Hotspots
Authors: Jain Manjari , Utpal Singha , Mukhopadhyay S.
Published: May 2011

Indirect Evidences of Wildlife Activities in Shoals of Western Ghats, a Biodiversity Hotspots

The presence of wildlife fauna and its activities were ascertained with the density of the scat, dung and other markings or droppings of the wildlife abode therein. Attempt was made to find out spatial differences in the activities of the wildlife populations and to comment on the abundance of different preys and predators within shola forests of Western Ghat hill forests, a Biodiversity hotspot in India. An indirect sampling method, Transect Count Method, was employed to count dung/pellet group/scat and other markings in that area. Pachyderms were found to be mostly dominant in Varagaliar and Punnumala shola patches while scats of all the three important predators, viz., tiger (Panthera tigris tigris), Indian wild dog (Cuon alpinus) and leopard (Panthera pardus) were encountered only in Varagaliar shola. Greater abundance was recorded from Indira Gandhi Wildlife Sanctuary than Silent Valley National Park may be because of the restriction of animal movements in the former due to topographical barriers and its existence as isolated shola patches that led to a greater concentration of wild fauna in a relatively segregated forest cover.
Ecological assessment of wetland ecosystems of northern Kazakhstan on the basis of hydrochemistry and algal biodiversity
Authors: Barinova Sophia , Nevo Eibi , Bragina Tatiana
Published: May 2011

Ecological assessment of wetland ecosystems of northern Kazakhstan on the basis of hydrochemistry and algal biodiversity

We studied diversity of algae and cyanobacteria in the wetlands of protected natural lakes with salinity ranging from 0.19 up to 32.7 in the arid/semiarid regions of Northern Kazakhstan. In plankton and periphyton of 34 lakes, we found 254 species belonging to 113 genera of 8 algal divisions. The diversity in arid regions is represented by widespread species of diatoms, green algae, and cyanobacteria in similar proportions. Alkaliphiles, among the indicators of acidification, and betamesosaprobionts, among the indicators of saprobity, predominated. The indices of saprobity in lakes varied from 1.47 to 2.7, reflecting low-trophic and low anthropogenically disturbed wetlands. Oligohalobes-indifferents are most common. Highly diverse algal communities were found irrespective of various levels of mineralization. As a consequence of aridization, salinity increase suppressed algal diversity. The mineralization was the most important variable defining the diversity levels, irrespective of the type and location of wetland lakes in the arid regions.
Shift of the western boundary of the distribution area of Micromeria cristata (Hampe) Griseb. and Steptorhamphus tuberosus (Jacq.) Grossh
Authors: Petrović Danka , Stešević Danijela
Published: May 2011

Shift of the western boundary of the distribution area ofMicromeria cristata(Hampe) Griseb. andSteptorhamphus tuberosus(Jacq.) Grossh

During field investigations of Mt Rumija, two new taxa for the flora of Montenegro were recorded:Micromeria cristata(Hampe) Griseb. andSteptorhamphus tuberosus(Jacq.) Grossh. From the phytogeographic point of view these data indicate a change in the distribution area of both taxa, which have shifted to the west. Ashort over-view of the taxonomic treatment of both genera is given.
Universal Tunable Current-Mode Biquad Employing Distributed Feedback Structure with MO-CCCII
Authors: Šotner Roman , Slezák Josef , Dostál Tomáš , Petržela Jiří
Published: June 2011

Universal Tunable Current-Mode Biquad Employing Distributed Feedback Structure with MO-CCCII

One possible application of the multiple-output electronically-tunable active building block as a universal filter with distributed feedback structure is presented. The suggested structure is less conventional than the well-known state-variable Kerwin-Huelsman-Newcomb but allows the same filter configurations with the similar properties. The major current-mode design approach disadvantage,ie, the necessity of multiple current outputs, is demonstrated. To date even a rather big line of the commercially available devices do not solve this problem. Some features of the active block used for modelling and transistor-level simulation are briefly discussed. The obvious chance for electronic tuning of the proposed filter is verified.
Angiographic features of “brain sag”
Authors: Alaraj Ali , Munson Troy , Herrera Sebastian R. , Aletich Victor , Charbel Fady T. , Amin-Hanjani Sepideh
Published: May 2011

Object

Cerebrospinal fluid hypotension, or “brain sag,” is a recently described phenomenon most commonly seen following craniotomy for the clipping of ruptured aneurysms along with preoperative lumbar drain placement. The clinical features and CT findings have been previously described. Clinical presentation can be similar to and often mistaken for cerebral vasospasm. In this study, the authors report on the angiographic findings in patients with brain sag.

Methods

Five cases of brain sag were diagnosed (range 1–4 days) after the surgical treatment of ruptured aneurysms at the University of Illinois at Chicago. All patients met the clinical and CT criteria for brain sag. Admission cerebral angiograms and subsequent angiograms during symptoms of brain sag were obtained in all patients. In 3 patients, angiography was performed after the resolution of symptoms.

Results

In all 5 patients, the level of the basilar artery apex was displaced inferiorly with respect to the posterior clinoid processes during brain sag. This displacement was significant enough to create a noticeable kink in the basilar artery (“cobra sign”) in 3 patients. Other angiographic findings included foreshortening or kinking of the intracranial vertebral artery. In all patients, the posterior cerebral arteries were displaced medially and inferiorly. Three patients were treated for simultaneous severe radiological vasospasm. In 4 patients, the brain sag was recognized, and the patients' conditions improved when they were placed flat or in the Trendelenburg position, at times combined with an epidural blood patch. Patients with follow-up angiography studies after the symptoms had resolved displayed a reversal of the angiographic features.

Conclusions

Brain sag appears to be associated with characteristic angiographic features. Recognizing these features may help to diagnose brain sag as the cause of neurological deterioration in this patient population.
Preliminary evaluation of a novel intraparenchymal capacitive intracranial pressure monitor
Authors: Aquilina Kristian , Thoresen Marianne , Chakkarapani Ela , Pople Ian K. , Coakham Hugh B. , Edwards Richard J.
Published: May 2011

Object

Intracranial pressure (ICP) monitors are currently based on fluid-filled, strain gauge, or fiberoptic technology. Capacitive sensors have minimal zero drift and energy requirements, allowing long-term implantation and telemetric interrogation; their application to neurosurgery has only occasionally been reported. The aim of this study was to undertake a preliminary in vitro and in vivo evaluation of a capacitive telemetric implantable ICP monitor.

Methods

Four devices were tested in air- and saline-filled pressure chambers; long-term capacitance-pressure curves were obtained. Devices implanted in a gel phantom and in a piglet were placed in a 3-T MR unit to evaluate MR compatibility. Four devices were implanted in a piglet neonatal hydrocephalus model; output was compared with ICP obtained through fluid-filled transduction and a strain-gauge ICP monitor.

Results

The capacitance-pressure relationship was constant over 4 weeks, suggesting minimal zero drift during this period. There were no temperature changes around the monitor. Signal loss at the sensor was minimal in both the phantom and the piglet. Over 114,000 measurements were obtained; the difference between mean capacitive ICP and fluid-transduced ICP was 1.8 ± 1.42 mm Hg. The correlation between ICP from the capacitive sensor and fluid-filled transducer (r = 0.97, p < 0.0001) or strain-gauge monitor (r = 0.99, p < 0.0001) was excellent. In vivo monitoring was restricted to 48 hours due to problems with robustness in the clinical environment.

Conclusions

This preliminary study demonstrates minimal long-term zero drift in vitro, good MR compatibility, and good correlation with other methods of ICP monitoring in vivo in the short term. Further long-term in vivo study is required.
Meta-analysis of instrumented posterior interbody fusion versus instrumented posterolateral fusion in the lumbar spine
Authors: Zhou Zhi-Jie , Zhao Feng-Dong , Fang Xiang-Qian , Zhao Xing , Fan Shun-Wu
Published: May 2011

Object

The authors compared the effectiveness of instrumented posterior lumbar interbody fusion (iPLIF) and instrumented posterolateral fusion (iPLF) for the treatment of low-back pain (LBP) due to degenerative lumbar disease.

Methods

Relevant randomized controlled trials (RCTs) and comparative observational studies through December 2009 were identified using a retrieval strategy of sensitive and specific searches. The study design, participant characteristics, interventions, follow-up rate and period, and outcomes were abstracted after the assessment of methodological quality of the trials. Analyses were performed following the method guidelines of the Cochrane Back Review Group.

Results

Nine studies were identified—3 RCTs and 6 comparative observational studies. No significant difference was found between the 2 fusion procedures in the global assessment of clinical outcome (OR 1.51, 95% CI 0.71–3.22, p = 0.29) and complication rate (OR 0.55, 95% CI 0.16–1.86, p = 0.34). Both techniques were effective in reducing pain and improving functional disability, as well as restoring intervertebral disc height. Instrumented PLIF was more effective in achieving solid fusion (OR 2.60, 95% CI 1.35–5.00, p = 0.004), a lower reoperation rate (OR 0.20, 95% CI 0.03–1.29, p = 0.09), and better restoration of segmental angle and lumbar lordotic angle than iPLF. There were no significant differences between the fusion methods regarding blood loss (weighted mean difference –179.63, 95% CI –516.42 to 157.15, p = 0.30), and operating time (weighted mean difference 8.03, 95% CI –45.46 to 61.53, p = 0.77).

Conclusions

The authors' analysis provided moderate-quality evidence that iPLIF has the advantages of higher fusion rate and better restoration of spinal alignment over iPLF. No significant differences were identified between iPLIF and iPLF concerning clinical outcome, complication rate, operating time, and blood loss.
A Comparative Study of Efficacy and Adverse Effects Between Alfuzosin and Tamsulosin in the Treatment of Benign Prostatic Hyperplasia
Authors: Rahman Md Mizanur , Alam SM Mahbub , Amin Md Nurul
Published: June 2011

Keywords: Tamsulosin, alfuzosin; lower urinary tract symptoms; benign prostatic hyperplasiaIbrahim Card Med J 2011; 1(1):27-32
State of the Art in Tumor Antigen and Biomarker Discovery
Authors: Even-Desrumeaux Klervi , Baty Daniel , Chames Patrick
Published: June 2011

Our knowledge of tumor immunology has resulted in multiple approaches for the treatment of cancer. However, a gap between research of new tumors markers and development of immunotherapy has been established and very few markers exist that can be used for treatment. The challenge is now to discover new targets for active and passive immunotherapy. This review aims at describing recent advances in biomarkers and tumor antigen discovery in terms of antigen nature and localization, and is highlighting the most recent approaches used for their discovery including “omics” technology.
Impact of Turbulence Intensity and Equivalence Ratio on the Burning Rate of Premixed Methane–Air Flames
Authors: Fru Gordon , Thévenin Dominique , Janiga Gábor
Published: May 2011

Direct Numerical Simulations (DNS) have been conducted to study the response of initially laminar spherical premixed methane–air flame kernels to successively higher turbulence intensities at five different equivalence ratios. The numerical experiments include a 16-species/25-step skeletal mechanism for methane oxidation and a multicomponent molecular transport model. Highly turbulent conditions (with integral Reynolds numbers up to 4513) have been accessed. The effect of turbulence on the physical properties of the flame, in particular its consumption speed Sc, which is an interesting measure of the turbulent flame speed ST has been investigated. Local quenching events are increasingly observed for highly turbulent conditions, particularly for lean mixtures. The obtained results qualitatively confirm the expected trend regarding correlations between u′/SL and the consumption speed: Sc first increases, roughly linearly, with u′/SL (low turbulence zone), then levels off (bending zone) before decreasing again (quenching limit) for too intense turbulence. For a fixed value of u′/SL, Sc/SL varies with the mixture equivalence ratio, showing that additional parameters should probably enter phenomenological expressions relating these two quantities.
Flavonoid Analyses and Antimicrobial Activity of Various Parts of Phaleria macrocarpa (Scheff.) Boerl Fruit
Authors: Hendra Rudi , Ahmad Syahida , Sukari Aspollah , Shukor M. Yunus , Oskoueian Ehsan
Published: May 2011

Phaleria macrocarpa (Scheff.) Boerl (Thymelaceae) is commonly known as ‘Crown of God’, ‘Mahkota Dewa’, and ‘Pau’. It originates from Papua Island, Indonesia and it grows in tropical areas. Empirically, it is potent in treating the hypertensive,diabetic, cancer and diuretic patients. It has a long history of ethnopharmacological usage, and the lack of information about its biological activities led us to investigate the possible biological activities by characterisation of flavonoids and antimicrobial activity of various part of P. macrocarpa against pathogenic bacteria and fungi. The results showed that kaempferol, myricetin, naringin, and rutin were the major flavonoids present in the pericarp while naringin and quercetin were found in the mesocarp and seed. Furthermore, the antibacterial activity of different parts of P. macrocarpa fruit showed a weak ability to moderate antibacterial activity against pathogenic tested bacteria (inhibition range: 0.93–2.17 cm) at concentration of 0.3 mg/disc. The anti fungi activity was only found in seed extract against Aspergillus niger (1.87 cm) at concentration of 0.3 mg/well. From the results obtained, P. macrocarpa fruit could be considered as a natural antimicrobial source due to the presence of flavonoid compounds.